FitSugar

Understanding Emotional Eating

FitSugar — Thu, 01 May 2008 09:00:00 -0700

Food, the nourishment for our lives, can be loaded with issues. In our troubled relationships with food, emotional eating ranks at the top of the list. Understanding the phenomenon and recognizing the symptoms are great ways to start redefining your relationship with food. The first thing to understanding the problem is recognizing the traits of emotional eating.

Psychiatrist Roger Gold, an authority on this issue, outlined some characteristics of emotional eating at diet.com. They are:

Hunger that comes on suddenly: Physical hunger comes on slowly. Hunger from emotional eating often comes on quickly and suddenly.
Craving very specific foods: Cravings for specific, usually unhealthy foods is a sign of emotional eating. Often people like the rush they get from satisfying their cravings. That rush is fulfilling emotional hunger.
Urgent hunger: Physical hunger, unless you haven't eaten for a very long time, is usually pretty patient. It will wait for food. Emotional hunger demands to be satisfied immediately.

There are a couple more, so read more.

Unconscious eating: When you're eating for physical reasons, you are usually mindful of what you're doing. If you catch yourself eating "just because," then it's likely you're eating for emotional reasons.
A sense of guilt after satisfying your hunger: Feeding your body what it needs is not something to feel guilty about. If you feel guilty after you eat, it's likely because part of you knows you're not eating just to satisfy physical hunger.

If these traits are prominent in your relationship with food, now might be a good time to try to break the habit. Pay attention to your emotional triggers by keeping a journal of what you eat, when, and why – trying to very specific if it was physiological hunger that lead you to eat or an emotional incident. Journaling will help you figure out your eating pattern.

Source

Eating disorders

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Eating Disorders Overview

Eating disorders typically occur among young women.
Bulimia nervosa involves a pattern of bingeing and purging. Many people with bulimia nervosa also suffer from depression.
Anorexia nervosa involves a pattern of self-starvation. Patients often have an accompanying anxiety disorder (such as obsessive compulsive disorder) or depression. Patients who have anorexia and depression have a high risk for suicide. Some studies estimate that anorexia nervosa has the highest death rate of any psychiatric disorder.

Treatment of Bulimia Nervosa

Bulimia nervosa is treated with a combination of psychotherapy and medication. Cognitive behavioral therapy, which is given along with nutritional counseling, is the preferred psychotherapeutic approach. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), are the first choice for drug therapy.

Treatment of Anorexia Nervosa

Unlike bulimia nervosa, anorexia nervosa does not respond as well to drug treatment, although SSRIs are sometimes used as an adjunct to psychotherapy. Therapy that includes the entire family -- not just the patient -- is an important part of the treatment process, as is nutritional education. Patients who are severely underweight and who have other physical risks may need to be hospitalized while weight is restored. Recovery is a long process that can take 5 - 6 years to achieve.

Introduction

Eating disorders are behavioral issues brought on by a complex interplay of factors, which may include emotional and personality disorders, family pressures, a possible genetic or biologic susceptibility, and a culture in which there is an overabundance of food and an obsession with thinness. There are four general categories of eating disorders:

Bulimia nervosa
Anorexia nervosa
Binge eating
Eating disorders not otherwise specified

These are not new disorders. Although anorexia nervosa was first defined as a medical problem in the late 1800s, descriptions of self-starvation have been found even in medieval writings.

Bulimia nervosa is more common than anorexia, and it usually begins early in adolescence. It is characterized by cycles of bingeing and purging, and typically takes the following pattern:

Bulimia is often triggered when young women attempt restrictive diets, fail, and react by binge eating. (Binge eating involves consuming larger than normal amounts of food within a 2-hour period.)
In response to the binges, patients compensate, usually by purging, vomiting, using enemas, or taking laxatives, diet pills, or drugs to reduce fluids.
Patients then revert to severe dieting, excessive exercise, or both. (Some patients with bulimia follow bingeing only with fasting and exercise. They are then considered to have non-purging bulimia.)
The cycle then swings back to bingeing and then to purging again.
Some studies have reported that patients with bulimia average about 14 episodes of binge-purging per week. To be diagnosed with bulimia, however, a patient must binge and purge at least twice a week for 3 months. (Some experts believe that going through the cycle only once a week is sufficient for a diagnosis.)
In some cases, the condition progresses to anorexia. Most people with bulimia, however, have a normal to high-normal body weight, although it may fluctuate by more than 10 pounds because of the binge-purge cycle.

Young people who occasionally force vomiting after eating too much are not considered bulimic, and most of the time this occasional unhealthy behavior does not continue beyond youth.

The term "anorexia" literally means absence of appetite. Anorexia nervosa involves an aversion to food that leads to a state of starvation and emaciation. It is a very serious illness that some experts believe is an entirely different condition from bulimia and should be not be diagnosed as a simple eating disorder.

Facts associated with anorexia nervosa:

At least 15% to as much as 60% of normal body weight is lost.
The patient with anorexia nervosa has an intense fear of gaining weight, even when severely underweight.
Individuals with anorexia nervosa have a distorted image of their own weight or shape and deny the serious health consequences of their low weight.
Women with anorexia nervosa miss at least three consecutive menstrual periods. (Some experts believe women can be anorexic without this occurrence.)

Patients with this condition are often characterized as anorexia restrictors or anorexic bulimic patients. Each type is equally prevalent.

Anorexia restrictors reduce their weight by severe dieting.
Anorexic bulimic patients maintain emaciation by purging. Although both types are serious, the bulimic type, which imposes additional stress on an undernourished body, is the more damaging.

Severe anorexia is common in the elderly, who may experience weight loss because of social isolation, impaired gastrointestinal function, or loss of certain chemicals related to the feeding drive. Such age-related anorexia, however, is not synonymous with anorexia nervosa, a psychologic disorder.

Bingeing without purging is characterized as compulsive overeating (binge eating) with the absence of bulimic behaviors, such as vomiting or laxative abuse (used to eliminate calories). Binge eating usually leads to becoming overweight.

To be diagnosed as a binge eater, a person typically has the following characteristics:

Bingeing at least twice a week for 6 months
Consuming 5,000 - 15,000 calories in one sitting
Eating three meals a day plus frequent snacks
Overeating continually throughout the day, rather than consuming large amounts of food during binges

Since binge eating disorder is generally associated with weight gain, it will not be further discussed in this report. [For more information, see In-Depth Report #53: Weight control and diet.]

A fourth category called eating disorders not otherwise specified (NOS) has been established to define eating disorders not specifically defined as anorexia or bulimia. This category includes:

Infrequent binge-purge episodes (occurring less than twice a week or having such behavior for less than months)
Repeated chewing and spitting without swallowing large amounts of food
Normal weight and anorexic behavior

Such patients tend to be older at diagnosis. Although less serious than other eating disorders, these patients still face similar health problems, including a higher risk for fractures and other conditions.

Risk Factors

Many factors contribute to the risk of developing an eating disorder. In the United States, about 7 million women and 1 million men suffer from eating disorders.

Eating disorders occur most often in adolescents and young adults. However, new research finds that they are increasingly prevalent among young children. Eating disorders are more difficult to identify in young children because they are rarely suspected.

Studies indicate that eating disorders occur predominantly among girls and women. About 90 - 95% of patients with anorexia nervosa, and about 80% of patients with bulimia nervosa, are female.

Most studies of individuals with eating disorders have been conducted using Caucasian middle-class females. Studies now indicate, however, that minority populations (including Hispanic Americans and African-Americans) are increasingly affected.

Living in any economically developed nation on any continent appears to pose a risk for eating disorders. Within nations, eating disorders can affect people of all socioeconomic levels.

People with eating disorders tend to share similar personality and behavioral traits, including low self-esteem, dependency, and problems with self-direction. Specific psychiatric personality disorders may put people at higher risk for eating disorders.

Avoidant Personalities. Some studies indicate that many patients with anorexia nervosa have avoidant personalities. This personality disorder is characterized by:

Being a perfectionist
Being emotionally and sexually inhibited
Having less of a fantasy life than people with bulimia or those without an eating disorder
Being perceived as always being "good," not being rebellious
Being terrified of being ridiculed or criticized or of feeling humiliated

People with anorexia are extremely sensitive to failure, and any criticism, no matter how slight, reinforces their own belief that they are "no good".

Obsessive-Compulsive Personality. Obsessive-compulsive personality defines certain character traits (being a perfectionist, morally rigid, or preoccupied with rules and order). This personality disorder has been strongly associated with a higher risk for anorexia. These traits should not be confused with the anxiety disorder called obsessive-compulsive disorder (OCD), although they may increase the risk for this disorder.

Borderline Personalities. Borderline Personality Disorder (BPD) is associated with self-destructive and impulsive behaviors. People with BPD tend to have other co-existing mental health problems, including eating disorders.

Narcissistic Personalities. Studies have also found that people with bulimia or anorexia are often highly narcissistic and tend to:

Have an inability to soothe oneself
Have an inability to empathize with others
Have a need for admiration
Be hypersensitive to criticism or defeat

Many patients with eating disorders experience depression and anxiety disorders. Depression, anxiety, or both is also common in families of patients with eating disorders. It is not clear if emotional disorders, particularly obsessive-compulsive disorder (OCD), cause the eating disorders, increase susceptibility to them, or share common biologic cause.

Obsessive-Compulsive Disorder (OCD). Obsessive-compulsive disorder is an anxiety disorder that occurs in up to two thirds of patients with anorexia and up to one third of patients with bulimia. In fact, some experts believe that eating disorders are variants of OCD. Obsessions are recurrent or persistent mental images, thoughts, or ideas, which may result in compulsive behaviors (repetitive, rigid, and self-prescribed routines) that are intended to prevent the manifestation of the obsession. Women with anorexia and OCD may become obsessed with exercise, dieting, and food. They often develop compulsive rituals (weighing every bit of food, cutting it into tiny pieces, or putting it into tiny containers). The presence of OCD with either anorexia or bulimia does not, however, appear to have any influence on whether a patient improves or not.

Obsessive-compulsive disorder is an anxiety disorder characterized by an inability to resist or stop continuous, abnormal thoughts or fears combined with ritualistic, repetitive, and involuntary defense behavior.

Other Anxiety Disorders. A number of other anxiety disorders have been associated with both bulimia and anorexia, including:

Phobias. Phobias often precede the onset of the eating disorder. Social phobias, in which a person is fearful about being humiliated in public, are common in both types of eating disorders.
Panic Disorder. Panic disorder often follows the onset of an eating disorder. It is characterized by periodic attacks of anxiety or terror (panic attacks).
Post-Traumatic Stress Disorder. Many women with serious eating disorders report a past traumatic event, and many exhibit symptoms of post-traumatic stress disorder (PTSD) -- an anxiety disorder that occurs in response to life-threatening circumstances.

Depression. Depression is common in people with eating disorders, for both anorexia and bulimia. Major depression is unlikely to be a cause of eating disorders, however, because treating and relieving depression rarely cures an eating disorder. In addition, depression often improves after anorexic patients begin to gain weight.

Extreme eating disorder behaviors, including use of diet pills, laxatives, diuretics, and vomiting, are reported more often in overweight teenagers. Researchers are working on strategies for preventing the development of eating disorders among overweight adolescents. A 2006 study that targeted overweight college-age women reported success with an Internet-based cognitive behavioral therapy program that helped these women become more comfortable with their body weight and shape. The program also included information on the risks of eating disorders, and education on healthy eating and weight maintenance.

Body Dysmorphic Disorder. Body dysmorphic disorder (BDD) involves a distorted view of one's body that is caused by social, psychologic, or possibly biologic factors. It is often associated with anorexia or bulimia, but it can also occur without any eating disorder. People with this disorder commonly suffer from emotional disorders, including obsessive-compulsive disorder and depression. As part of obsessive thinking, some people with BDD may obsess about a perceived deformity in one area of their body, and may repeatedly seek cosmetic surgery to "correct" it. People with BDD are also at higher risk for suicidal thinking and attempts. Some evidence suggests that treatment with fluoxetine (Prozac), a common antidepressant known as an SSRI helps reduce this problem, even in people without an eating disorder.

Muscle Dysmorphia. Experts are also increasingly reporting a disorder in which people have distorted body images involving their muscles. It tends to occur in men who perceive themselves as being "puny," which results in excessive body building, preoccupation with diet, and social problems. Such individuals are prone to eating disorders and other unhealthy behaviors, including the use of anabolic steroids.

Highly competitive athletes are often perfectionists, a trait common among people with eating disorders.

Female Athletes. Excessive exercise is associated with many cases of anorexia (and, to a lesser degree, bulimia). In young female athletes, anorexia postpones puberty, allowing them to retain a muscular boyish shape without the normal accumulation of fatty tissues in breasts and hips that may blunt their competitive edge. Many coaches and teachers compound the problem by overstressing calorie counting and loss of body fat.

In response, people who are vulnerable to such criticism may lose excessive weight, which has been known to be deadly even for famous athletes. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Eating disorders, including anorexia
Amenorrhea (absence or irregular menstruation)
Osteoporosis (bone loss, which appears to be related to low weight)

Male Athletes. Male wrestlers and lightweight rowers are also at risk for excessive dieting. One-third of high school wrestlers use a method called weight-cutting for rapid weight loss. This process involves food restriction and fluid depletion by using steam rooms, saunas, laxatives, and diuretics. Although male athletes are more apt to resume normal eating patterns once competition ends, studies show that the body fat levels of many wrestlers are still well below their peers during off-season and are often as low as 3% during wrestling season.

Men and Women in the Military. Studies also show a higher-than-average risk for eating disorders in men and women in the military. A study of eating behavior on one Army base reported that 8% of the women had an eating disorder, compared to 1 - 3% in the civilian female population.

In general, vegetarianism, with careful planning, is a healthy practice for both adults and adolescents. Studies report, however, that vegetarianism in adolescence may be a risk factor for eating disorders in both males and females. Vegetarian teens have been found to be twice as likely to diet frequently, four times as likely to intensively diet, and eight times as likely to use laxatives as their non-vegetarian peers.

These studies do not mean that being a vegetarian equates with having an eating disorder. They do suggest, however, that parents with children who suddenly become vegetarians should be sure that their children are eating a balanced meal with sufficient protein, calories, and important minerals, such as calcium. Parents also might suspect anorexic behavior in their child under certain conditions:

If the child has stopped eating meat only to avoid fat rather than from other motives, such as love of animals or to improve health.
If the vegetarian diet coincides with rapid weight loss.
If the child avoids important vegetable products because of calories (such as whole grains) or because of fats and oils (such as tofu, nuts, and dairy products).

Eating disorders may be more common in teenagers with chronic illness, such as diabetes or asthma. Some recent research suggests an endocrinological link between obesity, diabetes, and eating disorders.

Diabetes. Eating disorders are particularly serious problems for people with either type 1 or type 2 diabetes.

Binge eating (without purging) is most common in type 2 diabetes and, in fact, the obesity it causes may even trigger this diabetes in some people.
Both bulimia and anorexia are common in type 1 diabetes. A 2005 study indicated that as many as 25% of young women with type 1 diabetes may develop abnormal eating habits, and that the combination of diabetes and an eating disorder can have serious health consequences in the women's future. Diabetic women often omit or underuse insulin in order to control weight. If such patients develop anorexia, their extremely low weight may appear to control the diabetes for a while. Eventually, however, if they fail to take insulin and continue to lose weight, these patients develop life-threatening complications.

Click the icon to see an image of type 1 diabetes.

There is a greater risk for eating disorders and other emotional problems for girls who undergo early puberty, when the pressures experienced by all adolescents are intensified by experiencing, possibly alone, these early physical changes, including normal increased body fat. One interesting study reported that:

Before puberty, girls ate quantities of food appropriate to their body weight, were satisfied with their bodies, and noted their depression increased with lower food intake.
After puberty, girls ate about three-quarters of the recommended calorie intake, had a worse body self-image, and noted their depression increased with higher food intake.

This study reported on girls without eating disorders, but it certainly suggests patterns that can lead to eating problems, particularly in girls who go through puberty early. Other studies also indicate that girls who start menstruating at a younger age are more likely to develop eating disorders.

Causes

There is no single cause for eating disorders. Although concerns about weight and body shape play a role in all eating disorders, the actual cause of these disorders appear to result from many factors, including cultural and family pressures and emotional and personality disorders. Genetics and biologic factors may also play a role.

Negative influences within the family may play a major role in triggering and perpetuating eating disorders. Some studies have produced the following observations and theories regarding family influence.

Insecure Infancy. Some experts theorize that parents who fail to provide a safe and secure foundation in infancy may foster eating disorders. In such cases, children experience so-called insecure attachments. They are more likely to have greater weight concerns and lower self-esteem than are those with secure attachments.
Parental Behaviors. Poor parenting by both mothers and fathers has been implicated in eating disorders. One study found that 40% of 9- and 10-year-old girls trying to lose weight generally with the urging of their mothers. Some studies have found that mothers of anorexics tend to be over-involved in their child's life, while mothers of people with bulimia are critical and detached. Overly critical fathers, brothers, or both may play a factor in the development of anorexia in both girls and boys.
Family Meals. How often a family eats together may influence whether a child develops an eating disorder. A study published in the Journal of Adolescent Health found that young girls who ate 3 - 4 meals per week with their families were about half as likely to engage in extreme weight control behaviors as girls who ate family meals less often.
Family History of Addictions or Emotional Disorders. Studies report that people with either anorexia or bulimia are more likely to have parents with alcoholism or substance abuse than are those in the general population. Parents of people with bulimia appear to be more likely to have psychiatric disorders than parents of patients with anorexia.
History of Abuse. Women with eating disorders, particularly bulimia, appear to have a higher incidence of sexual abuse. Studies have reported sexual abuse rates as high as 35% in women with bulimia.
Family History of Obesity. People with bulimia are more likely than average to have an obese parent or to have been overweight themselves during childhood.

At least one study has reported that the most positive way for parents to influence their children's eating habits and to prevent weight problems and eating disorders is to have healthy eating habits themselves.

Anorexia is eight times more common in people who have relatives with the disorder, and some experts estimate that genetic factors are the root cause of many cases of eating disorders. Twins had a tendency to share specific eating disorders (anorexia nervosa, bulimia nervosa, and obesity). Researchers have identified specific chromosomes that may be associated with bulimia and anorexia. In particular, regions on chromosome 10 have been linked to bulimia as well as obesity. Some evidence has also reported an association with genetic factors responsible for serotonin, the brain chemical involved with both well-being and appetite. Researchers have also pinpointed certain proteins such as brain-derived neurotrophic factor (BDNF). This protein may influence an individual's susceptibility to developing an eating disorder.

The approach to food in Western countries is extremely problematic. Enough food is produced in the U.S. to supply 3,800 calories every day to each man, woman, and child, far more than any single person needs to sustain life. Obesity is a global epidemic, and few people living in this over-fed and sedentary culture eat a meal guiltlessly.

One interesting anthropologic study reported the following observations:

During historical periods or in cultures where women are financially dependent and marital ties are stronger, the standard is toward being curvaceous, possibly reflecting a cultural or economic need for greater reproduction.
During periods or in cultures where female independence has been possible, the standard of female attractiveness tends toward thinness.

The response of the media to the cultural drive for thinness and the overproduction of food both likely play major roles in triggering obesity and eating disorders.

On the one hand, advertisers heavily market weight-reduction programs and present anorexic young models as the paradigm of sexual desirability.
Clothes are designed and displayed for thin bodies in spite of the fact that few women could wear them successfully.
On the other hand, the media floods the public with attractive ads for consuming foods, especially "junk" foods.

Hormonal abnormalities are common in eating disorders and include chemical abnormalities in the thyroid, the reproductive regions, and areas related to stress, well-being, and appetite. Many of these chemical changes are certainly a result of malnutrition or other aspects of eating disorders, but they also may play a role in perpetuating or even creating susceptibility to the disorders.

The primary setting of many of these abnormalities originate in a small area of the brain called the limbic system. A specific system called hypothalamic-pituitary-adrenal axis (HPA) may be particularly important in eating disorders. It originates in the following regions in the brain:

Hypothalamus. The hypothalamus is a small structure that plays a role in controlling our behavior, such as eating, sexual behavior and sleeping, and regulates body temperature, emotions, secretion of hormones, and movement.

Click the icon to see an image of the hypothalamus.

The pituitary gland. The pituitary gland is involved in controlling thyroid functions, the adrenal glands, growth, and sexual maturation.
Amygdala. This small almond-like structure lies deep in the brain and is associated with regulation and control of major emotional activities, including anxiety, depression, aggression, and affection.

Click the icon to see an image of the brain-thyroid link.

Stress Hormones. The HPA systems trigger the production and release of stress hormones called glucocorticoids, including the primary stress hormone cortisol. Chronically elevated levels of stress chemicals have been observed in patients with anorexia and bulimia. Cortisol is very important in marshaling systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with any threat.

Release of Neurotransmitters. The HPA system also releases certain neurotransmitters (chemical messengers) that regulate stress, mood, and appetite and are being heavily investigated for a possible role in eating disorders. Abnormalities in the activities of three of them, serotonin, norepinephrine, and dopamine, are of particular interest. Serotonin is involved with well-being, anxiety, and appetite (among other traits), and norepinephrine is a stress hormone. Dopamine is involved in reward-seeking behavior. Recent research suggests that people with anorexia have increased activity in the brain's dopamine receptors. This overactivity may explain why people with anorexia do not experience a sense of pleasure from food and other typical comforts.

Ghrelin. High levels of ghrelin, a hormone that increases the feeling of hunger and slows metabolism, have been noted in patients with anorexia and bulimia.

Low-Leptin Levels. Leptin is a hormone that appears to trigger the hypothalamus to stimulate appetite, and low levels have been observed in people with anorexia and bulimia.

Low Reproductive Hormones. The hypothalamic-pituitary system is also responsible for the production of important reproductive hormones that are severely depleted in anorexics. Although most experts believe that these reproductive abnormalities are a result of anorexia, others have reported that in 30 - 50% of people with anorexia, menstrual disturbances occurred before severe malnutrition set in and remained a problem long after weight gain, indicating that hypothalamic-pituitary abnormalities precede the eating disorder itself.

In some cases, infection has been associated with anorexia. In such cases, immune factors released to fight these infections may cause inflammation and injury in the areas of the brain that affect appetite and behavior.

Streptococcal Infection. The bacteria responsible for strep throat and rheumatic fever -- called group A beta-hemolytic streptococcal (GABHS) -- is now a suspect in some cases of anorexia. Some children who have been infected with these bacteria develop a syndrome that includes obsessive-compulsive disorder (OCD), tics, and anorexia nervosa. The syndrome is called PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus). More research is needed to confirm this as an actual cause of anorexia and to determine if it may be treatable with antibiotics.

Epstein Barr Virus. Epstein Barr, the virus that causes mononucleosis, has also been associated with the development of anorexia.

Click the icon to see an image of infectious mononucleosis.

Complications of Bulimia

Most studies report that patients who have bulimia without severe weight loss have a much better outlook than patients with anorexia. Some studies have suggested that 60 - 80% of bulimic patients are in remission within 3 months of treatment. However, relapse is common, and over half of women with bulimia continue to battle disordered eating habits for years. In one study, bulimia itself persisted in 10 - 25% of patients after treatment.

Many medical problems are directly associated with bulimic behavior, including:

Tooth erosion, cavities, and gum problems
Water retention, swelling, and abdominal bloating
Acute stomach distress
Fluid loss with low potassium levels (due to excessive vomiting or laxative use; can lead to extreme weakness, near paralysis, or lethal heart rhythms)
Irregular periods
Swallowing problems and esophagus damage

Forced vomiting causes repetitive assaults on the esophagus (the food pipe) from forced vomiting. It is not clear, however, if swallowing problems are common.

The esophagus connects the nose and mouth with the stomach. The epiglottis folds over the trachea when a swallow occurs, to prevent the swallowed substance from being inhaled into the lungs. When a person is unable to swallow because of illness or coma, a tube may be inserted either through the mouth or nose, past the epiglottis, through the esophagus and into the stomach. Nutrients pass directly through the tube into the stomach.

Rupture of the esophagus, or food pipe
Weakened rectal walls (rare, but serious condition that requires surgery)

Click the icon to see an image of the rectum.

A number of self-destructive behaviors occur with bulimia:

Smoking. Many teenage girls with eating disorders smoke because it is thought to help prevent weight gain.
Impulsive Behaviors. Women with bulimia are at higher-than-average risk for dangerous impulsive behaviors, such as sexual promiscuity, self-cutting, and kleptomania. Some studies have reported such behaviors in half of those with bulimia.
Alcohol and Substance Abuse. An estimated 30 - 70% of patients with bulimia abuse alcohol, drugs, or both. This rate is higher than that of the general population and for people with anorexia. However, this higher rate of substance abuse may be a distortion because studies are conducted only on diagnosed patients. Bulimia tends not to get diagnosed. And reports of bulimia in the community (where the incidence of the eating disorder is higher than statistics suggest) indicate that substance abuse is actually lower than in people with anorexia.

Women with bulimia frequently abuse over-the-counter medications, such as laxatives, appetite suppressants, diuretics, and drugs that induce vomiting (ipecac). None of these drugs is without risk. For example, ipecac poisonings have been reported, and some people become dependent on laxatives for normal bowel functioning. Diet pills, even herbal and over-the-counter medications, can be hazardous, particularly if they are abused.

Complications of Anorexia

Anorexia nervosa is a very serious illness that has a wide range of effects on the body and mind. It is also associated with other problems, ranging from frequent flus and general poor health to life-threatening conditions. Some experts believe that it should not be approached as a simple eating disorder but as a serious condition requiring staging according to severity.

At this time, no treatment program for anorexia nervosa is completely effective. Recovery rates vary between 23 - 50%, and relapses range from 4 - 27%. Recovery takes an average of 5 - 6 years from the time of diagnosis. Up to 30% of patients do not recover.

Even after treatment and weight gain, many patients continue to display characteristics of the disorder, including perfectionism and a drive for thinness, which could keep them at risk for recurrence.

Some research suggests that anorexia nervosa has the highest death rate of any psychiatric disorder. According to different studies, the risk for early death is higher for people with the following conditions or characteristics:

Being younger
Having bulimia anorexia (twice as high in this group than in the anorexic-restrictor types)
Being severely low in weight at the time of treatment
Being sick for more than 6 years
Having been previously obese
Having an accompanying severe psychological disorder including personality disorders

One of the most serious effects of anorexia is hormonal changes, which can have severe health consequences.

Reproductive hormones, including estrogen and dehydroepiandrosterone (DHEA), are lower. Estrogen is important for healthy hearts and bones. DHEA, a weak male hormone, may also be important for bone health and for other functions.
Thyroid hormones are lower.
Stress hormones are higher.
Growth hormones are lower. Children and adolescents with anorexia may experience retarded growth.

The result of many of these hormonal abnormalities in women is long-term, irregular or absent menstruation (amenorrhea). This can occur early on in anorexia, even before severe weight loss. Over time this causes infertility, bone loss, and other problems. Low weight alone may not be sufficient to cause amenorrhea. Extreme fasting and purging behaviors may play an even stronger role in hormonal disturbance.

Adolescents with eating behaviors associated with anorexia (fasting, frequent exercise to lose weight, and self-induced vomiting) are at high risk for anxiety and depression in young adulthood. Alcohol and drug abuse are more common in patients with anorexia. Suicide has been estimated to account for as many as half the deaths in anorexia with studies showing up to a fifth of anorexic patients attempting suicide.

Heart disease is the most common medical cause of death in people with severe anorexia. The effects of anorexia on the heart are:

Dangerous heart rhythms, including slow rhythms known as bradycardia, may develop. Such abnormalities can show up even in teenagers with anorexia.

Bradycardia is a slowness of the heartbeat, usually at a rate under 60 beats per minute (normal resting rate is 60 - 100 beats per minute).

Blood flow is reduced
Blood pressure may drop
The heart muscles starve, losing size
Cholesterol levels tend to rise

Click the icon to see an image of cholesterol.

A primary danger to the heart is from abnormalities in the balance of minerals, such as potassium, calcium, magnesium, and phosphate, which are normally dissolved in the body's fluid. The dehydration and starvation that occurs with anorexia can reduce fluid and mineral levels and produce a condition known as electrolyte imbalance. Electrolytes (calcium and potassium) are critical for maintaining the electric currents necessary for a normal heartbeat. An imbalance in these electrolytes can be very serious and even life threatening unless fluids and minerals are replaced. Heart problems are a particular risk when anorexia is compounded by bulimia and the use of ipecac, a drug that causes vomiting.

After treatment and an increase in weight, estrogen levels are usually restored and periods resume. In severe anorexia, however, even after treatment, normal menstruation never returns in 25% of such patients.

If a woman with anorexia becomes pregnant before regaining normal weight, she faces a higher risk for miscarriage, cesarean section, and for having an infant with low birth weight or birth defects. She is also at higher risk for postpartum depression.
Women with anorexia who seek fertility treatments have lower chances for success.

Most pregnant women with a history of eating disorders have healthy pregnancies. However, some studies suggest that they may face higher risks for a number of complications, including cesarean sections, postpartum depression, miscarriages, complicated deliveries, and premature birth. Many studies indicate that babies born to mothers with eating disorders have a higher risk for low birth weight. However, an encouraging 2006 study reported that mothers with a history of anorexia nervosa do not have a higher risk for pregnancy complications or poor birth outcomes.

Almost 90% of women with anorexia experience osteopenia (loss of bone minerals), and 40% have osteoporosis (more advanced loss of bone density). Up to two-thirds of children and adolescent girls with anorexia fail to develop strong bones during their critical growing period. Boys with anorexia also suffer from stunted growth. The less the patient weighs, the more severe the bone loss. Women with anorexia who also binge-purge face an even higher risk for bone loss.

Bone loss in women is mainly due to low estrogen levels that occur with anorexia. Other biologic factors in anorexia also may contribute to bone loss, including high levels of stress hormones (which impair bone growth) and low levels of calcium, certain growth factors, and DHEA (a weak male hormone). Weight gain, unfortunately, does not completely restore bone. Only achieving regular menstruation as soon as possible can protect against permanent bone loss. The longer the eating disorder persists the more likely the bone loss will be permanent.

Testosterone levels decline in boys as they lose weight, which also can affect their bone density. In young boys with anorexia, weight restoration produces some catch-up growth, but it may not produce full growth.

People with severe anorexia may suffer nerve damage that affects the brain and other parts of the body. The following nerve-related conditions have been reported:

Seizures
Disordered thinking
Numbness or odd nerve sensations in the hands or feet (peripheral neuropathy)

Brain scans indicate that parts of the brain undergo structural changes and abnormal activity during anorexic states. Some of these changes return to normal after weight gain, but there is evidence that some damage may be permanent. Still, the extent of the neurologic problems is unclear.

Anemia is a common result of anorexia and starvation. In one study, 38% of anorexic participants had anemia. A particularly serious blood problem is pernicious anemia, which can be caused by severely low levels of vitamin B12. If anorexia becomes extreme, the bone marrow dramatically reduces its production of blood cells, a life-threatening condition called pancytopenia.

Bloating and constipation are both very common problems in people with anorexia.

In very late anorexia, the organs simply fail. The main warning sign is high blood levels of liver enzymes, which require immediate administration of calories.

Eating disorders are very serious for young people with type 1 diabetes. A study of over 2,000 women found that bulimia, or a combination of bulimia and anorexia, was more common among women with type 1 diabetes.

The complications of eating disorders that affect all patients are even more dangerous in this group of patients. Low blood sugar, for example, is a danger for anyone with anorexia, but it is a particularly dangerous risk for those with diabetes. If patients do not take their insulin, high blood sugar, which is also very dangerous, can occur. Unfortunately, patients with eating disorders may skip or reduce their daily insulin in order to decrease their intake of calories. Extremely high blood sugar levels can cause diabetic ketoacidosis, a condition in which acidic chemicals (ketones) accumulate in the body. This condition can lead to coma and death.

Symptoms

Possibly the most bewildering symptom of eating disorders is the distorted body image (body dysmorphia ). Although people typically associate distorted body image with severe anorexia, one study indicated that distortion may be more prevalent in people with bulimia. People with bulimia were more likely than those with anorexia to overestimate their size. There was also a greater disparity between what they wanted to look like and what they believed they looked like.

People with bulimia nearly always practice it in secret, and, although they may be underweight, they are not always anorexic. Symptoms or signs of bulimia may, therefore, be very subtle and go unnoticed. They may include:

Evidence of discarded packaging for laxatives, diet pills, emetics (drugs that induce vomiting), or diuretics (medications that reduce fluids)
Regularly going to the bathroom right after meals
Suddenly eating large amounts of food or buying large quantities that disappear right away
Compulsive exercising
Broken blood vessels in the eyes (from the strain of vomiting)
Pouch-like appearance to the corners of the mouth due to swollen salivary glands (occurs within days of vomiting in about 8% of people with bulimia)
Dry mouth
Tooth cavities, diseased gums, and irreversible enamel erosion from excessive acid
Rashes and pimples
Small cuts and calluses across the tops of finger joints due to self-induced vomiting

Weight Loss. The primary symptom of anorexia is major weight loss from excessive and continuous dieting, which may either be restrictive dieting or binge-eating and purging.

Other symptoms of anorexia may include:

Infrequent or absent menstrual periods
Compulsive exercising coupled with excessive thinness
Refusal to eat in front of others
Ritualistic eating, including cutting food into small pieces
Hypersensitivity to cold -- some women wear several layers of clothing to both keep warm and hide their thinness
Yellowish skin, especially on the palms of the hands and soles of the feet -- from eating too many vitamin A-rich vegetables such as carrots
Dry skin covered with fine hair
Thin scalp hair
Cold or swollen feet and hands
Stomach problems, including bloating after eating
Confused or slowed thinking
Poor memory or judgment

Diagnosis

The first step towards a diagnosis is to admit the existence of an eating disorder. Often, the patient needs to be compelled by a parent or others to see a doctor because the patient may deny and resist the problem. Some patients may even self-diagnose their condition as an allergy to carbohydrates, because after being on a restricted diet, eating carbohydrates can produce gastrointestinal problems, dizziness, weakness, and palpitations. This may lead such people to restrict carbohydrates even more severely.

It is often extremely difficult for parents as well as the patient to admit that a problem is present. For example, because food is such an intrinsic part of the mother-child relationship, a child's eating disorder might seem like a terrible parental failure. Parents may have their own emotional issues with weight gain and loss and perceive no problem with having a "thin" child.

It is recommended that a supportive companion be present during part of the initial medical interview to offer additional information on the patient's eating history and to help offset any resistance or denial the patient may express.

Various questionnaires are available for assessing patients. The Eating Disorders Examination (EDE), which is an interview of the patient by the doctor, and the self-reported Eating Disorders Examination-Questionnaire (EDE-Q) are both considered valid tests for assessing eating disorder diagnosis and determining specific features of the individual’s condition (such as vomiting or laxative use).

Another test is called the SCOFF questionnaire. It is proving to be very reliable in accurately identifying both very young and adult patients who meet the full criteria for anorexia or bulimia nervosa. (It may not be as accurate in people who do not meet the full criteria.)

SCOFF Questionnaire

Do you make yourself Sick because you feel uncomfortably full?

Do you worry you have lost Control over how much you eat?

Have you recently lost more than One stone 's worth of weight (14 pounds) in a 3-month period?

Do you believe yourself to be Fat when others say you are too thin?

Would you say that Food dominates your life?

Answering yes to two of these questions is a strong indicator of an eating disorder.

In spite of the prevalence of bulimia, a majority of doctors have never diagnosed bulimia in a patient. Younger and female doctors are more likely to detect bulimia. A doctor should make a diagnosis of bulimia if there are at least two bulimic episodes per week for 3 months. Because people with bulimia tend to have complications with their teeth and gums, dentists could play a crucial role in identifying and diagnosing bulimia.

Generally, an observation of physical symptoms and a personal history will quickly confirm the diagnosis of anorexia. The standard criteria for diagnosing anorexia nervosa are:

The patient's refusal to maintain a body weight normal for age and height
Intense fear of becoming fat even though underweight
A distorted self-image that results in diminished self-confidence
Denial of the seriousness of emaciation and starvation
The loss of menstrual function for at least 3 months

The doctor then categorizes the anorexia further:

Restricting (severe dieting only)
Anorexia bulimia (binge-purge behavior)

Because the disorder rarely shows up in men, doctors may not be on the lookout for it in male patients, even if they show classic symptoms of anorexia. Doctors should be very aware of these symptoms in anyone, particularly in athletes and dancers.

Once a diagnosis is made, doctors should immediately check for any serious complications of starvation. They should also rule out other medical disorders that might be causing the anorexia. Tests should include:

A complete blood count
Tests for electrolyte imbalances (low potassium levels mean the disorder is more likely to be accompanied by the binge-purge syndrome)
Test for protein levels
An electrocardiogram and a chest x-ray
Tests for liver, kidney, and thyroid problems
A bone density test

Treatment

Treatment goals for eating disorders include:

Restore normal weight for anorexia nervosa
Reduce, and hopefully stop, binge eating and purging for bulimia nervosa
Treat physical complications and any associated psychiatric disorders
Teach patients proper nutritional habits and how to develop healthy eating patterns and meal plans
Change patients’ dysfunctional thoughts about the eating disorder
Improve self-control, self-esteem, and behavior
Provide family counseling
Prevent relapse

The first major difficulty in treating eating disorders is resistance by everyone involved:

The anorexic patient often believes that the emaciation is normal and even attractive.
The bulimic patient may feel that purging is the only way to prevent obesity.
Even worse, the anorexic condition may be encouraged by friends who envy thinness or by dance or athletic coaches who encourage low body fat.
The family itself may deny the problem and be obstructive or manipulative, adding to the difficulties of treatment.

It is very important that the patient and any close friends and relatives be informed about the serious potential of these conditions and the importance of receiving immediate help.

A multidisciplinary team approach with consistent support and counseling is essential for long-term recovery from all severe eating disorders. Depending on the severity and type of disorder, team members may include:

Doctors specializing in relevant medical complications
Dietitians
Cognitive-behavioral therapists
Psychotherapists
Nurses

All should be skilled in treating eating disorders. Studies have found that people treated by such specialists have a lower mortality rate than those treated only as psychiatric patients.

Patients may drop out of programs if they have unrealistic expectations of being "cured" simply through the therapists' insights. Before a program begins, the following possibilities should be made clear:

The process is painful and requires hard work on the part of the patient and family.
A number of therapeutic methods are likely to be tried until the patient succeeds in overcoming these difficult disorders.
Relapse is common but should not be greeted with despair. (In one study, about 90% of bulimic patients responded to treatments after 6 years.)

Although the outcome for bulimics is generally more favorable than for anorexics, long-term studies are showing recovery in most people treated for anorexia.

Psychotherapies. Eating disorders are nearly always treated with some form of psychiatric or psychologic treatment. Depending on the problem, certain psychologic approaches may work better than others.

Medications. Various medications may be helpful for patients depending on the type of eating disorder, psychiatric state, and severity of the condition.

Nutritional Rehabilitation. Nutritional counseling can help patients regain weight and learn normal expectations concerning hunger and eating patterns.

The patient’s condition, social circumstances, and health insurance coverage determine the type of treatment facility -- inpatient hospitalization, residential hospitalization, partial hospitalization, or outpatient care. Weight is not the sole determining factor. The patient’s overall physical condition, psychological state, behavior patterns, and family support are all factors. Patients and their families should discuss with their doctors the various options available and how structured and intense the treatment should be.

Treatment for Bulimia

Some experts recommend a stepped approach for patients with bulimia, which follow specific stages depending on the severity and response to initial treatments:

Support groups. This is the least expensive approach and may be helpful for patients who have mild conditions with no health consequences.
Cognitive-behavioral therapy (CBT) along with nutritional therapy is the preferred first treatment for bulimia that does not respond to support groups.
Drugs. The drugs used for bulimia are typically antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). A combination of CBT and SSRIs is very effective if CBT alone is not helpful.

Patients with bulimia rarely need hospitalization except under the following circumstances:

Binge-purge cycles have led to anorexia
Drugs are needed for withdrawal from purging
Major depression is present

Psychologic Therapy. Cognitive-behavioral therapy (CBT) is the first-line of therapy for most patients with bulimia and is successful in about 60% of cases. Patients who do not respond to CBT tend to be less committed to the treatment, are more preoccupied with their symptoms, and have ritualized eating behaviors. Interpersonal therapy may be tried if CBT fails. Some studies have found that bulimic patients respond well to self-help CBT with a CD-ROM or manual. These methods, the research found, reduced the incidence of both binging and vomiting. Patients who do not respond to CBT may wish to try interpersonal therapy (also known as “talk therapy’), where therapists help patients explore how social and family relationships may affect their eating disorder.

Antidepressants. The most common antidepressants prescribed for bulimia are selective serotonin reuptake inhibitors (SSRIs) such as:

Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)

Studies are mixed, however, on whether SSRIs offer an additional advantage in reducing binge-eating compared to CBT. Fluoxetine has been approved for bulimia and is considered the drug of choice, although some studies suggest that other SSRIs work just as well.

Antidepressants may increase the risks for suicidal thoughts and actions during the first few months of treatment. In particular, adolescents and young adults should be carefully monitored during this time period for any changes in behavior.

Topiramate. The antiepileptic drug topiramate (Topamax) has been shown in studies to reduce bingeing and purging episodes in patients with bulimia. However, due to this drug’s risk for serious side effects, topiramate should be used only if other medication has failed. In addition, because people tend to lose weight while taking topiramate, it should not be used by patients who have low or even normal body weight.

Treatment for Anorexia

Treatment goals for patients with anorexia require a team approach. Doctors should immediately check and treat any medical problems related to the condition, such as bone loss, imbalances in important electrolytes, and any hormonal deficiencies, including thyroid and reproductive hormones. Nutrition rehabilitation and psychotherapy also plays an important part in anorexia therapy.

Many moderately to severely ill anorexic patients require hospitalization when:

Weight loss continues even with outpatient treatment
Weight is 30% below ideal body weight
Depression is severe or the patient is suicidal
There are symptoms of medical complications (disturbed heart rate, low potassium levels, altered mental status, low blood pressure, severe sensations of cold)

When severe metabolic or medical problems occur, patients with anorexia may need to be hospitalized either voluntarily or involuntarily. A variety of partial hospitalization or day care programs are also available.

Duration of Inpatient Treatment. For people with severe anorexia, many experts believe that 10 - 12 weeks of hospitalization with full nutritional support are required to reach ideal body weight. Check to see how many days your insurance company allows for inpatient treatment. Many rarely cover more than 15 days in the hospital. It is particularly important for women with both diabetes and anorexia to achieve 100% of ideal weight before being released.

The body mass index (BMI) is the measurement of body fat. It is derived by multiplying a person's weight in pounds by 703 and then dividing it twice by the height in inches.

A healthy BMI for women over age 20 is 19 - 24.
Those over 24 are considered to be at risk for health problems related to obesity.
Those under 17.5 are considered to be at risk for health problems related to anorexia. (However, young teenagers can have lower BMIs without necessarily being anorexic.)

For example, a woman who is 5'5" and weighs 125 pounds has a healthy BMI of 21. A woman at the same height who weighs 90 pounds would have a dangerously low BMI of 15.

Nutritional intervention is essential. Weight gain is associated with fewer symptoms of anorexia and with improvements in both physical and mental function. Restoring good nutrition can help reduce bone loss, and raising the level of energy available to the body by balancing food intake and exercise can normalize hormonal function. Restoring weight is also essential before the patient can fully benefit from additional psychotherapeutic treatments.

Goals for Weight Gain and Good Nutrition. A weight-gain goal of 2 - 3 pounds a week for hospitalized patients, and 0.5 - 1 pound a week for outpatients, is strongly encouraged. Patients typically begin with a calorie count as low as 1,000 - 1,600 calories a day, which is then gradually increased to 2,000 - 3,500 calories a day. Patients may initially experience intensified anxiety and depressive symptoms, as well as fluid retention, in response to weight gain. These symptoms decrease as the weight is maintained.

Tubal Feedings. Feeding tubes that pass through the nose to the stomach are not commonly used, since many experts believe they discourage a return to normal eating habits and because many patients interpret their use as punishing forced feeding. However, for patients who are at significant risk or for those who refuse to eat, tube feeding through the nose or through a tube inserted through the abdomen into the stomach can help with weight gain and improve the nutritional status of the patient. One method is to administer such feedings only at nighttime, with the patient eating normally during the day.

Intravenous Feedings. Intravenous feedings may be needed in life-threatening situations. This involves inserting a needle into the vein and infusing fluids containing nutrients directly into the bloodstream. Intravenous feedings must be administered carefully. When given at home, no more than the prescribed amount should be used. Overzealous administration of glucose solutions can trigger the so-called refeeding syndrome, in which phosphate levels drop severely and cause a condition called hypophosphatemia. Emergency symptoms include irritability, muscle weakness, bleeding from the mouth, disturbed heart rhythms, seizures, and coma.

The role of exercise in recovery is complex, since, for those with anorexia, excessive exercise is often a component of the original disorder. However, very controlled exercise regimens may be used as both a reward for developing good eating habits and as a way to reduce the stomach and intestinal distress that accompanies recovery. Exercise should not be performed if severe medical problems still exist and if the patient has not gained significant weight. The goal of exercise should be on improving physical fitness and health, not on burning off calories.

Psychologic Therapies Used in Anorexia. Family therapy is an important component of anorexia treatment, especially for children and adolescents. Adults usually begin with motivational psychotherapy that provides an empathetic setting and rewards positive efforts towards weight gain. After weight is restored, cognitive behavioral therapy techniques are helpful.

Antidepressants. Studies have not reported many benefits for treating anorexia nervosa with selective serotonin reuptake inhibitors (SSRIs), the antidepressants that are often useful for patients with bulimia. A few studies suggest that these drugs could be useful for people with anorexia nervosa who also have obsessive-compulsive disorder (OCD).

Doctors hoped that SSRIs could help prevent relapse in patients who have successfully restored their body weight. However, in a well-designed study in the Journal of the American Medical Association there was no difference in the time to relapse between patients who received fluoxetine (Prozac) and those who received placebo.

Nutritional Supplements. Calcium and vitamin D supplements are often recommended. Some studies have reported that zinc supplements may help patients gain weight.

Therapy

Eating disorders are nearly always treated with some form of psychiatric or psychologic treatment. Depending on the problem, different psychologic approaches may work better than others.

Cognitive-behavioral therapy (CBT) works on the principle that a pattern of false thinking and belief about one's body can be recognized objectively and altered, thereby changing the response and eliminating the unhealthy reaction to food. One approach for bulimia is the following:

Over a period of 4 - 6 months the patient builds up to eating 3 meals a day, including foods that the patient has previously avoided.
During this period, the patient monitors and records the daily dietary intake along with any habitual unhealthy reactions and negative thoughts toward eating while they are occurring.
The patient also records any relapses (binges or purging). Such lapses are reported objectively and without self-criticism and judgment.
The patient discusses the responses with a cognitive therapist at regular sessions. Eventually the patient is able to discover the false attitudes about body image and the unattainable perfectionism that underlies the opposition to food and health.
Once these habits are recognized, food choices are broadened, and the patient begins to challenge any entrenched and automatic ideas and responses. The patient then replaces them with a set of realistic beliefs along with actions based on reasonable self-expectations.

Interpersonal therapy deals with depression or anxiety that might underlie the eating disorders along with social factors that influence eating behavior. This therapy does not deal with weight, food, or body image at all.

The goals are the following:

To express feelings
To discover how to tolerate uncertainty and change
To develop a strong sense of individuality and independence
To address any relevant sexual issues or traumatic or abusive event in the past that might be a contributor of the eating disorder

Studies generally report that interpersonal therapy is not as effective as cognitive therapy for bulimia and binge eating, but may be useful for some patients with anorexia. The skill of the therapist plays a strong role in its success.

Because of the major role family attitudes play in eating disorders, one of the first steps in treating the patient with early-onset anorexia is to also treat the family. Family therapy can be useful for both younger and older patients.

If the patient is hospitalized, experts recommend that family therapy start after the patient has gained weight, but before discharge. It should usually continue after the patient has left the hospital.

The feelings of intense guilt and anxiety that caregivers experience are probably similar to those produced by living with a person who is suicidal. An over-involved parent may even support the patient's eating disorder for various reasons:

Some parents may be afraid of releasing some underlying anger or grief directed at the patient.
Other parents may identify with the goal of thinness and not even perceive that their child is unhealthily underweight.

In such cases, it is extremely important that the family members fully understand the danger of this disorder and that they are collaborating in their child's illness, or even death, by encouraging this state.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.anad.org -- National Association of Anorexia Nervosa and Associated Disorders
www.aedweb.org -- Academy for Eating Disorders
www.nationaleatingdisorders.org -- Eating Disorders Awareness and Prevention
www.eatright.org -- American Dietetic Association
www.aabt.org -- Association for Behaviorial and Cognitive Therapies
www.psych.org -- The American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry

References

American Psychiatric Association. Treatment of patients with eating disorders, third edition. American Psychiatric Association. Am J Psychiatry. 2006 Jul;163(7 Suppl):4-54.

Berkman ND, Lohr KN, Bulik CM. Outcomes of eating disorders: a systematic review of the literature. Int J Eat Disord. 2007 May;40(4):293-309.

Bulik CM, Berkman ND, Brownley KA, Sedway JA, Lohr KN. Anorexia nervosa treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007 May;40(4):310-20.

Morris J, Twaddle S. Anorexia nervosa. BMJ. 2007 Apr 28;334(7599):894-8.

Signorini A, De Filippo E, Panico S, De Caprio C, Pasanisi F, Contaldo F. Long-term mortality in anorexia nervosa: a report after an 8-year follow-up and a review of the most recent literature. Eur J Clin Nutr. 2007 Jan;61(1):119-22. Epub 2006 Aug 2.

Schmidt U, Lee S, Beecham J, et al. A randomized controlled trial of family therapy and cognitive behavior therapy guided self-care for adolescents with bulimia nervosa and related disorders. Am J Psychiatry. 2007 Apr;164(4):591-8.

Review Date:
12/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Attention deficit hyperactivity disorder

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

In This Report

Highlights
Introduction
Risk Factors
Causes
Diagnosis
Other Disorders Associated ...
Complications
Treatment
Medications
Behavioral Management
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved lisdexamfetamine (Vysvanse), a new stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). The active ingredient in lisdexamfetamine is similar to dextroamphetamine, the drug used in Dexedrine and Adderall.

Drug Warning

In 2007, the FDA instructed the manufacturers of all ADHD drugs to include drug warning labels describing the risks for heart and psychiatric side effects. Doctors should carefully evaluate patients for any risk factors. Reports have linked ADHD drugs to sudden death in patients with serious heart problems. There is also a slightly increased risk for auditory hallucinations, paranoia, and manic behavior even in patients with no history of psychiatric problems. The FDA warning applies to all stimulant ADHD drugs and to the non-stimulant drug atomoxetine (Strattera).

Ritalin Can Stunt Growth

After 3 years of methylphenidate (Ritalin) treatment, children are about an inch shorter and 6 pounds lighter than their peers who do not take this drug, according to a 2007 study in the Journal of the American Academy of Child and Adolescent Psychiatry.

ADHD Improves Over Time

ADHD symptoms may improve over time regardless of the treatment approach, indicates a 2007 study in the Journal of the American Academy of Child and Adolescent Psychiatry. Researchers found that medication, behavioral therapy, or a combination of the two all helped produce improvement after 3 years. There appeared to be no significant difference between children who took medication and those who did not.

Neurofeedback May Help ADHD

Neurofeedback (also known as biofeedback) is a non-drug treatment that may help improve attention and behavior problems associated with ADHD. This treatment approach involves teaching children to control their brain wave activity.

Introduction

According to the U.S. National Institute of Mental Health, attention deficit hyperactivity disorder (ADHD) is a legitimate psychologic condition.

ADHD is a syndrome generally characterized by the following symptoms:

Inattention
Distractibility
Impulsivity
Hyperactivity

Some experts categorize ADHD into three subtypes:

Behavior marked by hyperactivity and impulsivity, but not inattentiveness
Behavior marked by inattentiveness, but not hyperactivity and impulsivity
A combination of the above two

There is some debate over these criteria. Some argue the condition is over-diagnosed. Others say it's underdiagnosed. (See Difficulties in Identifying Children with ADHD later in this article.) One-third of cases are accompanied by learning disabilities and other neurologic or emotional problems, making an ADHD diagnosis particularly difficult. It is likely that the term attention-deficit hyperactivity disorder will eventually give way to subgroups of problems that include some of these general symptoms.

In the United States, about 4.7 million children ages 3 - 17 have been diagnosed at some point with ADHD. This accounts for 7.4% of all American children in this age range.

ADHD is a genuine disorder, but it is telling that the U.S. accounts for 90% of worldwide prescriptions for stimulants for ADHD. It is not known whether this reflects a real increase in ADHD, or a better ability to recognize it. Some say it may be an indication of a culture that places excessive value on normalcy and academic achievement at the expense of more frequent diagnoses.

Symptoms of ADHD usually occur before the age of 7. Studies indicate that ADHD symptoms in preschool children with ADHD do not differ significantly from older children.

The classic ADHD symptoms do not always adequately describe the child's behavior, nor do they describe what is actually happening in the child's mind. Some experts are focusing on deficits in "executive functions" of the brain to understand and describe all ADHD behaviors. Such impaired executive functions in ADHD children can cause the following problems:

Inability to hold information in short-term memory
Impaired organization and planning skills
Difficulty in establishing and using goals to guide behavior, such as selecting strategies and monitoring tasks
Inability to keep emotions from becoming overpowering
Inability to shift efficiently from one mental activity to another

Hyperactivity. The term hyperactive is often confusing since, for some, it suggests a child racing around non-stop. A boy with ADHD playing a game, for instance, may have the same level of activity as another child without the syndrome. But when a high demand is placed on the ADHD child's attention, his brain motor activity intensifies beyond the levels of the other children. In a busy environment, such as a classroom or a crowded store, ADHD children often become distracted and react by pulling items off the shelves, hitting people, or spinning out of control into erratic, silly, or strange behavior.

Impulsivity and Temper Explosions. Even before the "terrible twos," impulsive behavior is often apparent. The toddler may gleefully make erratic and aggressive gestures, such as hair pulling, pinching, and hitting. Temper tantrums, normal in children after age 2, are usually exaggerated and not necessarily linked to a specific negative event in the life of an ADHD child. One of the most painful events a parent may experience is an abrupt and aggressive attack that may occur after cuddling a young ADHD child. Often this reaction seems to be caused not by anger, but by the child's apparent inability to endure overstimulation or displays of physical affection.

Attention and Concentration. ADHD children are usually distracted and made inattentive by an overstimulating environment (such as a large classroom). They are also inattentive when a situation is low-key or dull. Some experts believe that certain parts of the brain in ADHD children may be underactive, so the children fail to be aroused by nonstimulating activities. In contrast, they may exhibit a kind of "super concentration" to a highly stimulating activity (such as a video game or a highly specific interest). Such children may even become over-attentive -- so absorbed in a project that they cannot modify or change the direction of their attention.

Impaired Short-Term Memory. Many experts now believe that an essential feature in ADHD, as well as in learning disabilities, is an impaired working (also called short-term) memory. People with ADHD can't hold groups of sentences and images in their mind long enough to extract organized thoughts. They are not necessarily inattentive. Instead, a patient with ADHD may be unable to remember a full explanation (such as a homework assignment), or unable to complete processes that require remembering sequences, such as model building. In general, children with ADHD are often attracted to activities (television, computer games, or active individual sports) that do not tax the working memory, or produce distractions. Children with ADHD have no differences in long-term memory compared with other children.

Inability to Manage Time. Studies suggest that children with ADHD have difficulties being on time and planning the correct amount of time to complete tasks. (This may coincide with short-term memory problems.) In one study, although children with probable ADHD were able to self-report many ADHD symptoms, they tended to believe they used their time wisely, in contrast to reports by their teacher.

Lack of Adaptability. ADHD children have a very difficult time adapting to even minor changes in routines, such as getting up in the morning, putting on shoes, eating new foods, or going to bed. Any shift in a situation can precipitate a strong and noisy negative response. Even when they are in a good mood, they may suddenly shift into a tantrum if met with an unexpected change or frustration. In one experiment, ADHD children could closely focus their attention when directly cued to a specific location, but they had difficulty shifting their attention to an alternative location.

Hypersensitivity and Sleep Problems. ADHD children are often hypersensitive to sights, sounds, and touch. They usually complain excessively about stimuli that seem low key or bland to others. Sleeping problems usually occur well after the point when most small children sleep through the night. In one study, 63% of children with ADHD had trouble sleeping.

A. Either 1 or 2 should be present:

1. Should have 6 or more of the following symptoms of inattention, persisting for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

Often fails to give close attention to detail, makes careless mistakes

Often has difficulty sustaining attention in tasks or play

Often does not seem to listen when spoken to directly

Often does not follow through and fails to finish tasks

Has difficulty organizing tasks and activities

Avoids or dislikes tasks requiring sustained mental effort

Often loses things necessary for tasks or activities

Is often easily distracted by extraneous stimuli

Is often forgetful in daily activities

2. Should have 6 or more of the following symptoms of hyperactivity-impulsivity that lasts for at least 6 months to a degree that is maladaptive and inconsistent with developmental level:

Often fidgets or squirms when sitting

Has difficulty remaining seated when required to do so

Often runs about or climbs excessively in inappropriate situations

Has difficulty playing quietly

Is often "on the go"

Often talks excessively

Often blurts out answers to questions before they have been completed

Has difficulty waiting for his or her turn

Often interrupts or intrudes on others

Note: Patients with A1 symptoms are diagnosed with ADHD, predominantly inattentive type. Those with A2 are diagnosed with ADHD, predominantly hyperactive-impulsive type. Those with both A1 and A2 are diagnosed as ADHD, combined-type.

B. Onset of some symptoms before the age of 7. However, children with the inattentive subtype are not often diagnosed until they are above 7 years of age.

C. Symptoms occur in two or more settings. For example, at home and at school.

D. Clear evidence of significant impairment in social or academic functioning.

E. Not caused by a pervasive developmental disorder, schizophrenia, or any other psychotic disorder, and is not better accounted for by another mental disorder, including anxiety or depression.

Source: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Ed. (Text Revision). Washington, DC: 2000.

Risk Factors

ADHD is most often diagnosed in boys. However, there is some evidence that it is underdiagnosed in girls. Until recently, all major studies were conducted using boys as subjects. Important studies on girls with ADHD are now underway. A major study reported that girls with the condition experience the same multiple impairments as boys do.

Although ADHD is primarily thought of as a childhood disorder, diagnoses of attention-deficit disorder in adults are on the rise. Methylphenidate (Ritalin) was prescribed for nearly 800,000 adults in the U.S. in 1997, nearly three times the number in 1992. As of 2005, experts estimated that ADHD affects about 4.1% of adults ages 18 - 44 years in a given year.

How Is ADHD Identified in Adults?

Research suggests that ADHD affects 2 - 6% of the adult population, assuming that one- to two-thirds of cases persist into adulthood. ADHD in adults always occurs as a continuum of the childhood condition. Adult-onset symptoms are likely due to other factors. Diagnosing adult ADHD can be a difficult problem since hyperactivity typically wanes as children get older, while attention and organizational problems may develop in older people. Some experts believe, then, that the number of adults with ADHD is underestimated.

A rating scale using four factors may be useful in identifying adults with ADHD:

Inattention and memory problems. (Examples: losing or forgetting things, being absent-minded, not finishing things, misjudging time, depending on others for order, having trouble getting started, changing jobs or projects in the middle.)
Hyperactivity and restlessness. (Examples: always being on the go, fidgety, easily bored, taking risks, liking active and fast paced jobs and activities, such as being a sales representative or stockbroker.)
Impulsivity and emotional instability. (Examples: saying things without thinking first, interrupting others, being annoying to others, easily frustrated, easily angered, having unpredictable moods, driving recklessly, having high relationship and job turnover.)
Problems with self worth. (Examples: Avoids new challenges, appears confident to others but not to oneself.)

Doctors use adult reports of their childhood behaviors and experiences when searching for clues for a diagnosis. Interestingly, the disorder seems to be distributed equally between adult women and men.

How Serious Is Attention Deficit Disorder in Adults?

Accompanying Emotional, Personality, and Learning Disorders. Between 19 - 37% of adults with ADHD have depression or bipolar disorder. Between 25 - 50% have an anxiety disorder. Bipolar disorder plus ADHD, in fact, may be very difficult to differentiate from ADHD alone in adults.

Accompanying Learning Disorders. About 20% of adults with ADHD have learning disorders, usually dyslexia and auditory processing problems. These problems should be considered in any treatment plan.

Effect on Work. Compared to adults without ADHD, those with the condition tend to reach lower educational levels, earn less money, and be fired more often. In fact, one article reported that by the time they are in their 30s, about 35% of ADHD adults are self-employed.

Substance Abuse. About 1 in 5 adults with ADHD also contend with substance abuse. Studies indicate that adolescents with ADHD are twice as likely to smoke cigarettes as their peers who do not have ADHD. Cigarette smoking during adolescence is a risk factor for the development of substance abuse in adulthood.

Sleep Disorders. Sleep disorders, especially restless legs syndrome and sleep apnea, are common in adults and children with ADHD. Sleep apnea is a disorder in which a person temporarily stops breathing during sleep, perhaps hundreds of times. In most cases the person is unaware of it, although sometimes they awaken and gasp for breath. It is usually accompanied by snoring. One report suggested that treating sleep apnea in adults with both conditions may help reduce ADHD symptoms. [For more information, see In-Depth Report #65: Sleep apnea.]

Causes

Brain Structures. Research using advanced imaging techniques shows there is a difference in the size of certain parts of the brain in children with ADHD compared to children who do not have ADHD. The areas showing change include the prefrontal cortex, the caudate nucleus and globus pallidus, and the cerebellum:

The prefrontal cortex is located in the front of the brain. It is thought to be the brain's command center. It regulates the brain’s ability to block certain responses. Numerous imaging studies have indicated that the prefrontal cortex of the brain in people with ADHD may be less active than in those without the disorder.
The caudate nucleus and globus pallidus, located near the center of the brain, speed up or stop orders coming from the prefrontal cortex. In some reports, these areas have been smaller than average in young children with ADHD, but tended to become normal as the children got older. Abnormalities in these areas may impair a person's ability to stop certain actions, resulting in the impulsivity typical of people with ADHD.
The cerebellum is the area above the brain stem. This area helps control muscle tone and balance, and synchronizes muscle activity. This has been found to be smaller in children with ADHD compared to those without the condition.

Brain Chemicals. Abnormal activity of certain brain chemicals in the prefrontal cortex may contribute to ADHD. The chemicals dopamine and norepinephrine are of special interest. Dopamine and norepinephrine are neurotransmitters, or chemical messengers, that affect both mental and emotional functioning. They also play a role in the "reward response." This response occurs when a person experiences pleasure in response to certain stimuli (such as food or love). Studies suggest that increased levels of the brain chemicals glutamate, glutamine, and GABA -- collectively called Glx -- interact with the pathways that transport dopamine and norepinephrine.

Nerve Pathways. Another area of interest is a network of nerves called the basal-ganglia thalamocortical pathways. Abnormalities along this neural route have been associated with ADHD, Tourette syndrome, and obsessive-compulsive disorders, all of which share certain symptoms.

Genetic factors may play the most important role in ADHD. The relatives of ADHD children (both boys and girls) have much higher rates of ADHD, antisocial, mood, anxiety, and substance abuse disorders than the families of non-ADHD children. A study reported that 90% of children with a diagnosis of ADHD shared it with their twin.

Genetic Factors Regulating Dopamine and Advantages in Early Man. Most of the research on the underlying genetic mechanisms targets the neurotransmitter dopamine. Variations in genes that regulate specific dopamine receptors have been identified in a high proportion of people with addictions and ADHD. Such genes have been associated with novelty seeking and extroversion. Some experts theorize that the genetic variants may have first appeared thousands of years ago, and affect as many as half of ADHD children. Furthermore, the genetic variations may have offered some benefits to their early carriers. In such people, a genetic predilection for novelty-seeking and risk-taking may have supplied an advantage in reproduction, mating, hunting, and achieving dominance.

Genetic Resistance to Thyroid Hormone. About 50% of adults and 70% of children with a genetic resistance to thyroid hormone, essential for normal brain development, have ADHD. People who have this condition appear to have a more severe form of ADHD. The thyroid disorder is not a common cause of ADHD. Only those with a family history of thyroid disease are at risk.

Infant malnutrition is a strong risk indicator of ADHD. Even if children receive enough food later on, infants who suffer from malnutrition may develop behavior problems, the most prevalent being attention-deficit disorder.

Deficiencies in Zinc and Essential Fatty Acids. Several dietary factors have been researched in association with ADHD, including sensitivities to certain food chemicals, deficiencies in fatty acids (compounds that make up fats and oils) and zinc, and sensitivity to sugar.

Some studies have found an association between deficiencies in certain fatty acids and ADHD. Other research reports an association between zinc deficiencies and ADHD. Zinc aids in the breakdown of fatty acids, which affects dopamine, the neurotransmitter likely to be involved with ADHD.

No clear evidence has emerged, however, that implicates any of these nutritional factors in ADHD.

Research suggests that prenatal exposure to tobacco, alcohol, environmental lead, and other toxins may increase the risk for ADHD and conduct disorders.

Diagnosis

Important factors for making a diagnosis of attention-deficit hyperactivity disorder (ADHD) include:

Children between ages 6 - 12 should first be evaluated for ADHD if they show symptoms of inattention, hyperactivity, impulsivity, academic underachievement, or behavior problems in at least two settings. Such behaviors should have been harmful for the child academically or socially for at least 6 months.
The child should meet the official symptom guidelines.
A diagnosis requires detailed reports by parents or caregivers. It should be noted that a mother's description of her child's behavior is a very accurate and reliable guide for diagnosing ADHD. Parents should not be shy about insisting on further evaluation if their experience does not match a doctor's single observation of their child.
Guidelines for primary care doctors emphasize the importance of obtaining direct evidence from the classroom teacher or other school-based professionals about the child's symptoms and their duration, and evidence of functional impairment in the school setting.
The child should be assessed for accompanying conditions (such as learning difficulties).

No laboratory or imaging tests exist to reliably diagnose ADHD. A diagnosis relies only on behavioral symptoms and ruling out other disorders. Many experts believe that the disorder is both over- and underdiagnosed. Diagnosis of attention-deficit hyperactivity disorder is difficult for some of the following reasons:

Factors Leading to the Over-Diagnosis of ADHD:

The popularity methylphenidate (Ritalin) has encouraged some parents and teachers to pressure doctors into prescribing this standard ADHD drug for children who are aggressive or who have poor grades. Often with careful testing many of these children do not meet the criteria for the illness. Children may have other diagnoses, other behavioral or emotional problems, or no problems at all.
Other factors that may contribute to misdiagnosis include children who are young for their grade and therefore socially and intellectually immature, and social and economic problems such as single parent households.

Factors Leading to the Under-Diagnosis of ADHD:

Some evidence suggests that many girls with ADHD may go underdiagnosed. Research indicates that girls with ADHD are often inattentive but not hyperactive or impulsive. In fact, older girls with ADHD tend to have social problems due to withdrawal and internalized emotions, showing symptoms of anxiety and depression. The inattentive subtype, in any case, may first show up in older children and adolescents.
Doctors may fail to diagnose children with ADHD because they often behave normally in the quiet doctor's office where there are no distractions to trigger symptoms. In addition, doctors may be unfamiliar with how to diagnose the condition.
In spite of the fact that there seems to be no differences in response to treatment among population groups, African-American, Hispanic, and Asian children with ADHD are half as likely to be diagnosed and treated as Caucasian children. By high school, the racial disparity increases to the level that the medication rate for blacks is one-fifth of that for whites.

The doctor will first require a detailed history of the child's behavior. Doctors will match this against a standardized checklist to define the disorder.

The parents should describe the following:

Specific problems, beginning as early as possible, they have encountered during the child's development -- school reports are very helpful
Sibling relationships
Recent life changes
A family history of ADHD
Eating habits
Sleep patterns
Speech and language development
Any problems during the mother's pregnancy or during delivery
Any history of medical or physical problems, particularly allergies, chronic ear infections, and hearing difficulties

The health professional will want to know how the parents handle different situations, and may want to observe them interacting with the child.

The child should also be given a general physical examination to determine if any medical conditions are present. The child should be given a hearing test to rule out hearing abnormalities as a source of behavioral problems.

Various tests are available to test neurologic, intellectual, and emotional development problems. Most involve learning and problem solving tasks that help define the particular areas that are most disabling. Blood or other laboratory tests are currently recommended only if the doctor suspects lead toxicity or other medical problems.

Although some doctors use a trial of a psychostimulant (usually Ritalin) to facilitate diagnosis, most experts strongly recommend against this method of diagnosis, because it is not always accurate. An improvement in symptoms is considered suggestive of ADHD, while in non-ADHD children the stimulant often increases agitation and hyperactivity. Many children and adults without the disorder have a similar response, and such a diagnostic trial may lead to unnecessary prescriptions of this drug.

Other Disorders Associated with ADHD

Several disorders may mimic or accompany attention-deficit disorder. ADHD exists alone in only about one-third of children. Many professionals object to the use of the single term "attention-deficit hyperactivity disorder" to encompass such a wide spectrum of behaviors, which they believe should be categorized into subgroups. Many of these problems require other modes of treatment and should be diagnosed separately, even if they accompany ADHD.

Attention-deficit disorder can appear without hyperactivity, in which case the child's primary symptoms are distractibility and an inability to persist in tasks.

About 14% of children diagnosed with ADHD also have oppositional-defiant disorder (ODD). The most common symptom for this disorder is a pattern of negative, defiant, and hostile behavior toward authority figures that lasts more than 6 months. In addition to displaying inattentive and impulsive behavior, these children demonstrate aggression, have frequent temper tantrums, and display antisocial behavior. A significant number of children with ODD also have anxiety disorders and depression, which should be treated separately. Many children who develop ODD at an early age go on to develop conduct disorder.

Some children with ADHD also have conduct disorder, which describes a complex group of behavioral and emotional disturbances seen in children. It includes aggression towards people and animals, destruction of property, deceitfulness, lying, or stealing, and general violation of rules.

Pervasive developmental disorder (PDD) is rare and usually marked by autistic-type behavior, hand-flapping, repetitive statements, slow social development, and speech and motor problems. If a child who has been diagnosed with ADHD does not respond to treatment, the parents might inquire about PDD, which often responds to antidepressants. Some children with PDD may also benefit from stimulants.

Children with ADHD often have difficulties with tasks that involve listening or hearing. Research is indicating that symptoms of the two disorders often overlap but may actually be two distinct disorders. Hearing problems themselves may cause ADHD symptoms.

Children diagnosed with attention-deficit disorder may also have bipolar disorder, commonly called manic depression. Indications of this problem include episodes of depression and mania (with symptoms of irritability, rapid speech, and disconnected thoughts), sometimes occurring at the same time. [For more information, see In-Depth Report #66: Bipolar disorder.] Both disorders often cause inattention and distractibility and may be difficult to distinguish, particularly in children. Children with mania and ADHD may have more aggression, behavioral problems, and emotional disorders than those with ADHD alone. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary way to differentiate bipolar disorder from ADHD is by the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not with ADHD. Most children with bipolar will also respond to the drug valproate, which does not typically work for ADHD in children.

Anxiety disorders commonly accompany ADHD. Obsessive-compulsive disorder is a specific anxiety disorder that shares many characteristics with ADHD and may share a genetic component. Young children who have experienced traumatic events, including sexual or physical abuse or neglect, exhibit characteristics of ADHD, including impulsivity, emotional outbursts, and oppositional behavior.

Sleep disorders or disturbances are very common with ADHD patients. Insomnia is common. In addition, specific sleep disorders -- restless legs syndrome and sleep-disordered breathing -- have been identified with hyperactivity and conduct disorder.

Restless Legs Syndrome (RLS). Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. One theory is that the two are linked by a common mechanism. The disorders have much in common, including poor sleep habits, twitching, and the need to get up suddenly and walk about frequently. They may even be genetically linked. For example, both have been associated with lower levels of dopamine in the brain, which is associated with faulty motor control, a common problem in both disorders.

Sleep-Disorder Breathing and Sleep Apnea. Some research has shown an association between mild symptoms of ADHD and sleep-disordered breathing, including snoring and obstructive sleep apnea in children and adults. Treating the sleep-related breathing disorders may improve the attention disorder in some children. (One study indicated that such problems are unlikely to be associated with children with moderate to severe ADHD.) [For more information, see In-Depth Report #65: Sleep apnea.]

Tourette Syndrome and Other Genetic Disorders. Several genetic disorders cause symptoms resembling ADHD, including fragile X and Tourette syndrome. About 50% of those with Tourette syndrome also have ADHD, and some of the treatments are similar.

Other Medical Conditions. A number of medical conditions, including hyperthyroidism and vision problems, can produce ADHD-like symptoms.

Lead. Children who ingest even low amounts of lead may manifest symptoms similar to those of ADHD. A child may be easily distractible, disorganized, and have trouble thinking logically. The major cause of lead toxicity is exposure to leaded paint, particularly in homes that are old and in poor repair.

Complications

More than half of children with attention-deficit disorder have accompanying disorders, including anxiety, depression, and conduct disorders. Children with ADHD who experience anxiety or depression are also more likely to suffer from low self-esteem.

Anti-Social Behavior. Even if these emotional disorders are absent in childhood, the ADHD child's relationship with others is volatile, and they are often unhappy from a very young age. Research indicates that any boy or girl with ADHD, particularly an aggressive child, has trouble getting along with others, and is less liked by his or her peers.

Children with the inattentive subtype of ADHD are more likely to be picked on and to spend time alone.
Children with the combined subtypes tend to have different problems. Boys with ADHD are less likely than others to empathize with people in difficult circumstances. A best friend can turn into an enemy overnight when, for example, a boy with ADHD does not perceive his friend's fearful response to over-aggressive roughhousing and fails to let up. The next day the child with ADHD has forgotten the event; the ex-friend hasn't. When a child with ADHD hurts someone, the child either may go into a state of denial or blame himself excessively. As ostracism, fear, and ridicule from peers persist from year to year, the unstable behavior, originally neurologic, becomes emotionally based. Unless this cycle is broken, serious adult problems can evolve.

Substance Abuse in Young People. Studies consistently report that young people with ADHD -- in particular those with conduct or mood disorders -- have a higher than average risk for substance abuse and that it starts in younger ages. In one study, for example, by age 11 nearly 20% of children with ADHD had tried smoking cigarettes, drinking alcohol, or both. Biologic factors associated with ADHD may make these individuals susceptible to substance abuse. Many of these young people are self-medicating their condition. In fact, according to a major analysis, Ritalin or other stimulants used to treat ADHD may help protect such patients against substance abuse. (Boys with ADHD and conduct disorder, however, still face a high risk for substance abuse. Girls with ADHD and emotional disorders may also still have a higher risk.)

High-Risk Behavior. Impulsivity in young people with ADHD can certainly cause them to take chances before thinking them through, putting them in situations where the consequences become clear only after the action has been taken. Children with ADHD and high levels of aggression are at higher risk for delinquent behavior in adolescents and criminal activity in adulthood. However, children with ADHD who are not aggressive have a lower and even normal risk for dangerous activities. Even in aggressive children with ADHD, close parental attention and early treatment can limit the risk considerably.

Although speech and learning disorders are common in children with ADHD, the disorder does not affect intelligence. People with ADHD span the same IQ range as the general population.

Many children with ADHD are underachievers, and half are held back in school at least once. Some evidence suggests that inattention may be a major factor in low academic performance in these children. About 20% also have reading difficulties, and 60% have serious handwriting problems. Adults with ADHD are also at very high risk for these conditions.

Some research suggests that ADHD persists in one- to two-thirds of those diagnosed with the condition in childhood. Many researchers describe the pattern of ADHD as they would a chronic illness, with remission and periods of worsening.

The time and attention needed to deal with a child with ADHD can change internal family relationships and have devastating effects on parents and siblings.

Effect on Parents. Studies indicate that any intervention for the child must include the parents. Parents who are responsive to their child in a positive way can help reduce the chances for oppositional behaviors. But it can be very difficult. A child with ADHD is wonderful one day and terrible the next, for no apparent reason. The parent can feel betrayed and hurt, and believe they have no control over their child. Parents must protect themselves and their child by establishing tough but kind rules about where their space ends and the child's begins. The are many effects on parents:

Mothers generally get the brunt of the emotional and physical abuse that a child with ADHD can produce.
Parents may have to give up on the idea of an immaculate house and a hot meal every night. Parents must learn that striving for perfection is among the most counterproductive goals to pursue in raising a child with ADHD, or any child.
Parents must face the hostility and anger of other parents and see their own child rejected. It is very easy to fall into an emotional black hole, and feel alone, inadequate, and helpless.
Marriages are often stressed to the breaking point because of exhaustion and disagreements between the husband and wife on how to respond to the child.

Effect on Siblings. Siblings of children with ADHD have particular difficulties, and are also at risk for psychologic impairment, depression, drug abuse, and language disorders. The non-ADHD sibling does not have the control a parent does in the management of the ADHD child's behavior and is very likely to feel alienated and alone. Children without ADHD are often victimized by siblings with ADHD who may be demanding or bullying.

A sibling who does not receive attention in their own right may begin to imitate undesirable behaviors or to act out negatively in other ways. It is very important to make the brothers and sisters equally vital to the family's functioning. However, they should never be made to feel that their value in the family is as caregivers of the ADHD sibling.

Treatment

A combination of a psychostimulant, most commonly methylphenidate (Ritalin), and cognitive-behavioral therapy is proving to be the best option for treatment of children with ADHD. Although medication can be helpful during the initial years of treatment, some research indicates that the benefits of medication eventually wear off. It appears that for ADHD symptoms may improve naturally over time, regardless of the treatment approach.

Signs that ADHD may be easing include not having to adjust medication dosages during growth spurts, no deterioration when a drug dose is missed, or new abilities to concentrate during “drug holidays.” (School vacation times are a good period to test the effectiveness of temporarily stopping medication.) The American Academy of Child and Adolescent Psychiatry suggests that parents evaluate whether medication can safely be withdrawn when children with ADHD have been free of symptoms for at least 1 year. If a child’s condition worsens after medication withdrawal, the drug should be resumed.

Developing a Treatment Approach. The following guidelines may be useful in determining a treatment approach for children with ADHD:

Behavioral techniques, possibly including dietary changes, should be tried first, if possible.
If the symptoms are severe or do not respond, a trial using medication (usually psychostimulants), in conjunction with behavior modification therapy, is advisable.

Cognitive behavioral therapy (CBT) is often administered by mental health providers, with both primary care physicians and psychiatrists prescribing medications. Unfortunately, many children do not have access to behavioral therapies, either because of lack of time or available resources.

Specific Patient Populations. Unfortunately, such guidelines do not address the following specific patient groups:

There are no definite guidelines for treating preschool children with severe ADHD. Some parents have reported very good long-term results with behavioral interventions at this age.
There are no reliable guidelines on how to treat the inattentive subtype of ADHD, which might be more common in girls.
There are no defined treatments for ADHD patients with accompanying conditions, including impaired working memory and deficits in language processing.
There are no defined treatments for children with ADHD and accompanying emotional problems, such as bipolar or anxiety disorders. (There is some evidence, for example, that children with ADHD plus anxiety disorders do worse on psychostimulants.)

Determining a Medication Regimen. Doctors still have a difficult time predicting which medications will produce beneficial results, so treatment is individualized and performed on a trial and error basis, which requires close observation and cooperation between all participants. In developing an effective medication plan, the following steps may be helpful:

Before any drug is administered, a child should be given a thorough examination for any medical problems to be sure there are no medical conditions that interfere with the medication.
Both the doctor and the parents should be very clear about the specific behaviors they hope the medication will target.
The goal is to use the lowest possible dosage that produces improved behavior.
If an initial regimen doesn't work, changing the dosage, or changing to a different medication often brings improvement.
Frequent follow-up visits should be scheduled to assess the response and to detect possible side effects.

Arguments For and Against Psychostimulants. Many parents are very disturbed by the idea of putting their children on intensive stimulant drug regimens, possibly for years, particularly given the uncertainties in diagnosis and the negative publicity surrounding the use of these drugs. Although the decision to use these drugs should not be made lightly, the negative social and emotional effects of the disorder itself for many children with ADHD are far more severe and long-lasting than the use of these drugs. For some parents and children, medication seems like a miracle and can provide desperate families with a quality of life for which they had almost given up hope. Whether or not psychostimulants are used, children and families should understand that ongoing efforts around behavior control will be necessary.

Of great concern is the dramatic increase in prescriptions for psychostimulants among preschool children. Although low doses of methylphenidate (Ritalin) may help preschoolers (ages 3 - 5 years) with ADHD, the drug can cause considerable side effects in many children. These side effects include insomnia, nervousness, anxiety, loss of appetite and weight, and slowed growth. Children in one large study grew about an inch less and weighed about 6 pounds less than normal after 3 years of methylphenidate treatment. Doctors must carefully consider the risks versus benefits when prescribing ADHD drugs to preschoolers. Children who do receive these drugs need to be carefully monitored by their doctors.

Treatment for Adult ADHD. As with children, adults with ADHD are treated with a combination of medication and psychotherapy. For medication, stimulant drugs or the non-stimulant drug atomoxetine (Strattera) are usually first-line treatments, with antidepressants a secondary option. Atomoxetine is approved specifically for adults with ADHD. Adults who have heart problems or heart condition risk factors should be aware of the cardiovascular risks associated with ADHD medication. There have been ADHD medication-associated incidents of sudden death in patients with underlying serious heart problems, and reports of stroke and heart attack in adults with cardiac risk factors.

Research increasingly supports the view that interventions for the ADHD child must also include the parents if they are to be successful. Teachers and school officials should also be educated and involved in the process.

Parents who feel they have the most control over their child's situation experience the least psychological stress and depression. Parents who are responsive in a positive way also help reduce the chances for their child developing oppositional behaviors. But it can be very difficult, particularly for parents who have ADHD themselves. In fact, parents who have severe ADHD symptoms are less likely to respond to parent training programs unless they get help for themselves.

In addition to behavioral therapy for the child, family therapy may help ADHD children and their parents and siblings cope with the emotional conflicts that nearly always arise in the lifelong process of managing the condition. Separate psychological therapies for specific family members might be needed, particularly in light of the high incidence of psychiatric and other emotional problems in families with ADHD children.

Medications

Several types of medication are available to treat ADHD.

Psychostimulants are the primary drugs used to treat ADHD. Although these drugs stimulate the central nervous system, they have a calming effect on people with ADHD.

These drugs include:

Methylphenidate (Ritalin, Concerta, Metadate, Daytrana)
Dexmethylphenidate (Focalin)
Amphetamine-Dextroamphetamine (Adderall)
Dextroamphetamine (Dexedrine, Dextrostat)
Lisdexamfetamine (Vyvanse)

Pemoline (Cylert), another stimulant drug, was withdrawn from the U.S. market in 2005 after several reports of liver failure.

Methylphenidate and Dexmethylphenidate. Methylphenidate drugs (Ritalin, Metadate, Concerta, Daytrana) are the most commonly used psychostimulants for treating ADHD in both children and adults. Dexmethylphenidate (Focalin) is a similar drug. These drugs increase dopamine, a neurotransmitter important for cognitive functions such as attention and focus.

With the exception of Daytrana, all of these drugs are pills taken by mouth. Daytrana, approved in 2006, is the first skin patch drug for ADHD. A patch is applied to the hip each day and delivers a 9-hour dose of methylphenidate.

These drugs are available in short-acting and long-acting dosage forms. The short-acting forms need to be taken several times a day, including during school hours. As the drug wears off, a rebound effect can occur, and ADHD symptoms can intensify. For this reason, the long-acting dosage forms have become popular.

Amphetamine, Dextroamphetamine, and Lisdexamfetamine. Amphetamine-dextroamphetamine (Adderall), dextroamphetamine (Dexedrine, Dextrostat), and lisdexamfetamine (Vyvanse) work by blocking the reabsorption of the brain chemicals dopamine and norepinephrine. Side effects can include stomach problems and mood changes, including sadness, anxiety, and irritability.

Psychostimulant medications are associated with some significant risks. All ADHD stimulant drugs carry warnings that they should not be used by patients with structural heart problems or pre-existing heart conditions (high blood pressure, heart failure, or heart rhythm disturbances). These drugs have been associated with sudden death in children with heart problems. They have also been associated with sudden death, stroke, and heart attack in adults with a history of heart disease. In addition, these drugs may slightly increase the risk for auditory hallucinations, paranoia, and manic behavior even in patients who do not have a history of psychiatric problems. The FDA has directed manufacturers of ADHD medications to warn all patients taking these medicines of their potential cardiovascular and psychiatric risks.

Stimulant drugs may also:

Worsen behavior and thought disturbance in patients with a pre-existing psychotic disorder.
Cause a mixed or manic episode in patients who have both ADHD and bipolar disorder.
Increase aggressive behavior or hostility. Patients beginning stimulant drug treatment should be monitored for worsening of these behaviors.
Slow growth and weight gain in children. Children who take stimulant drugs should have their growth monitored. If they do not gain height or weight at a normal rate, they may need to stop taking the drug.

Side Effects. All stimulants have a number of side effects:

The most common side effects of any stimulant are nervousness and sleeplessness, although some parents have reported improved sleep patterns in their children after taking stimulants.
Tics or jerky, disordered movements occur in about 9% of children.
Other side effects include irritability, stomach pain, headache, depression, hair loss, and lack of spontaneity.

Symptoms of Overdose. Symptoms of overdose include changes in heart rhythm and rate, hypertension, confusion, breathing difficulties, sweating, vomiting, and muscle twitches. If they occur, parents should call the doctor immediately. Even among young people who abuse Ritalin, however, less than 1% experience severe side effects (rapid heart rate, hypertension), and outcomes are generally good. Side effects may be very severe, however, if Ritalin is overused and taken with other drugs. A 2006 study reported that over 3,000 people are treated in hospital emergency rooms due to side effects from ADHD drugs. Sixty-one percent of these visits involved accidental ingestion or overdose.

Concerns for Abuse. Studies on both animals and humans suggest that Ritalin lacks the properties that create addiction, particularly in doses used for treating ADHD. Although methylphenidates have properties similar to amphetamines, their drug levels rise very slowly in the brain at the oral doses given for ADHD. This slow rise prevents a so-called "high" and subsequent addiction to the drug. Some stimulant drugs, such as lisdexamfetamine, may pose a lower risk for abuse than others.

The primary danger for drug abuse from stimulants appears to occur in non-ADHD young people who purchase these drugs illegally. In one study, for instance, 16% of children with ADHD reported pressure from their fellow students to sell or give them their medication. While people ages 18 - 25 are more likely to use ADHD drugs for non-medical uses, children ages 12 - 17 are more likely to suffer adverse effects from medication misuse and to require treatment at an emergency room. If a child abuses another drug (alcohol, prescription medication) along with the ADHD medication, the chance for serious side effects is even greater.

Atomoxetine (Strattera) was the first non-stimulant approved for ADHD in children and the first treatment approved for adult ADHD. The drug works by increasing levels of both norepinephrine and dopamine, which are generally lower than normal in ADHD. The most common side effect is decreased appetite. A few cases of atomoxetine-associated liver injury have been reported, and the FDA has warned doctors that the drug should be discontinued at the first signs of jaundice or liver problems. Long-term effects, such as any impact on growth, are still unknown. Atomoxetine may cause suicidal thinking in children and adolescents, especially during the first few months of treatment. Parents should monitor children taking atomoxetine for any changes in mood or behavior, and immediately contact their doctor if changes occur.

Antidepressants are not FDA-approved for ADHD treatment, but may be helpful in certain circumstances. Because antidepressants appear to work about as well as behavioral therapy, doctors recommend that patients first try psychotherapy before using antidepressants.

Bupropion (Wellbutrin) and tricyclics are the types of antidepressants used for ADHD. Bupropion affects the reuptake of the serotonin, norepinephrine, and dopamine neurotransmitters. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion should not be used by patients who have a seizure disorder.

Tricyclics are an older type of antidepressant that are effective but have many side effects. Imipramine (Tofranil) and nortriptyline (Pamelor, Aventil) are the tricyclics most commonly prescribed for ADHD. A third tricyclic, desipramine (Norpramin) should only be used if patients are not helped by other tricyclics. (Desipramine has caused sudden death in some children and adolescents.)

Tricyclic antidepressants can cause disturbances in heart rhythm. Children should have an electrocardiogram when they first begin to take this drug, and after any dose increase.

[For more information, see In-Depth Report #8: Depression ].

Alpha-2 agonists stimulate the neurotransmitter norepinephrine, which appears to be important for concentration. They include clonidine (Catapres) and guanfacine (Tenex). They are used for Tourette syndrome and may be beneficial when other drugs have failed for ADHD children with tics or those whose primary symptoms are severe impulsivity and aggression. These drugs are mainly prescribed in combination with a stimulant.

These drugs have a number of side effects. Sedation is the most common. A clonidine skin patch, which gradually releases the medication, helps reduce the sedative effect. Because clonidine slows the heart down, it can have adverse effects in some children. Going off too quickly or missing doses can cause rapid heartbeats and other symptoms that may lead to severe problems. Doctors strongly recommend that no child be given this medication without a preliminary examination for heart problems, and no child with existing heart, kidney, or circulatory problems should take it.

Behavioral Management

Behavioral techniques for managing the child with ADHD are not intuitive for most parents and teachers. To learn them, caregivers may need help from qualified health care professionals or from ADHD support groups. At first, the idea of changing the behavior of a highly energetic, obstinate child is daunting. It is futile and damaging to try to force a child with ADHD to be like most children. It is possible, however, to limit destructive behavior and to instill a sense of self-worth that will help overcome negativity toward life, which is one of the great dangers of the disorder.

Bringing up a child with ADHD, like bringing up any child, is a process. No single point is ever reached where the parent can sit back and say, "That's it. My child is now OK, and I don't have to do anything more." The child's self worth will evolve with an increasing ability to step back and consider the consequences of an action and then to control that action before taking it. But this does not happen overnight. A growing child with ADHD is different from other children in very specific ways, presenting challenges at every age.

Setting Priorities for the Parent. Parents must first establish their own levels of tolerance. Some parents are easygoing and can accept a wide range of behaviors, while others cannot. To help a child achieve self-discipline requires empathy, patience, affection, energy, and toughness. Some tips to help the parents include:

Parents should prepare a list giving priority to those behaviors they think are the most negative, such as fighting with other children or refusing to get up in the morning. The least negative behaviors on the bottom of the list should be ignored temporarily or even permanently (refusing to wear anything but red T-shirts).
Certain odd behaviors that are not hurtful to the child or to others may be an indication of creative or humorous attempts to adapt (making up silly songs or drawing violent pictures). These should be accepted as part of the child's unique and positive development, even if they seem peculiar to the parent.
It is important to keep in mind that no one is a saint. Loving parents who occasionally lose their tempers will not damage their children forever. In fact, non-abusive open disapproval or dismay is far less destructive to both parent and child than harboring resentment beneath a false calm.

Establishing Consistent Rules for the Child. Parents must be as consistent as possible in their approach to the child, which should reward good behavior and discourage destructive behavior. Rules should be well-defined but flexible enough to incorporate harmless idiosyncrasies. It is very important to understand that children with ADHD have much more difficulty adapting to change than do children without the condition. (For example, the child should do homework every day but might choose to start it after a TV show or computer game.)

Managing Aggression. Some useful tips for managing aggression include:

Parents should try to give little attention to mildly disruptive behaviors that allow this energetic child to let off some harmless steam. The parent will also be wasting energy that will be needed when the negative behavior becomes destructive, abusive, or intentional.
The use of "time-out," isolating the child immediately for a short period of time, is an effective measure for allowing both the caregiver and the child to cool down. The child should immediately (and without emotion) be removed from a situation in which they are endangered or endangering others. The child should view time out as a way of cooling off and getting a distance on their behavior, not as isolation from others.
To channel physical aggression and impulsivity in the ADHD toddler, the parents must teach them to use verbal responses. (A parent may need to allow verbal responses that would be unacceptable in another child.)
When the ADHD child becomes older and if the verbal responses become intentionally abusive and socially undesirable, the parent must redirect this form of aggression into more acceptable activities, such as competitive one-on-one sports, energetic music, video games, or big colorful paintings. Competitive video games, such as sports games, may also be an option.
Sometimes a parent can anticipate situations when an ADHD child is likely to misbehave, but all too often the child explodes for no apparent reason. If the blow-up occurs in public, the parents should complete their activities and leave as quickly as possible.

Establishing a Reward System. Children with ADHD respond particularly well to reward systems. One study reported that they performed equally well when encouraged either by a direct reward for a correct response or with the use of a system called response-cost. With this system, the child is given the reward first and allowed to keep it if their behavior remains appropriate.

Some suggested tips for rewarding the ADHD child are:

Create charts with points or stars for good behavior or for completed tasks. It is important to give points for even simple positive behaviors, which may be taken for granted in other children (responding happily to a change in plans, changing an obscenity to a more acceptable expletive).
Rewards for any child can include playing a favorite game with the child, extending bedtime by an hour, or allowing an extra half-hour of TV.
Rewards of food or gifts should be used infrequently, if at all. They can create other problems, such as being overweight, having a bad diet, or making continuous demands for objects.
A reward system should rotate different types of rewards, because such children are easily bored.
Children with ADHD respond better with small rewards promised in the short-term than large rewards offered in the future. One approach that employs both short- and long-term rewards uses a system that gives the child points for specific positive behaviors. As the children accumulate points, they can use them for larger tangible rewards, such as a favorite video game or CD.
Rewards should be promised only when caregivers are fairly certain they can follow through. ADHD children respond with much greater frustration than non-ADHD children to disappointment, and are likely to have a strong (and noisy) negative reaction. A parent must remember that this response is part of the ADHD child's make-up and not necessarily in their control.

Improving Concentration and Attention. Research indicates that ADHD children perform significantly better when their interest is engaged. Parents should be on the lookout for activities that hold the child's concentration. Some options that may help an ADHD child to focus include:

Many ADHD children are particularly lured by the computer, which is a very promising tool. A number of non-violent computer games are available that offer problem-solving techniques using characters, narrative, and humor.
Swimming, tennis, and other sports that focus attention and limit peripheral stimuli are often appealing. ADHD children often do not do well with team sports, although they are interested. Children with ADHD are less likely to become distracted in sports that require constant alertness, such as football or basketball. In baseball, positions such as pitching or catching are preferable to the outfield, where attention easily wanders. Finding a coach that understands the child’s difficulties is very helpful.
Some experts are enthusiastic about martial arts, such as Tae Kwon Do, which can offer an appropriate and controlled emotional outlet, help to focus attention, and teach self-restraint, self-discipline, and tolerance. Care should be taken to select an instructor who makes such goals a priority.
Learning an instrument may be one of the best ways for an ADHD child to develop a more rhythmic and balanced sense of self. Music, even simply listening to it, is often very important for these children. (Parents may have to tolerate music that does not please them.)

Even if a parent is successful in managing the child at home, difficulties often arise at school. The ultimate goal for any educational process should be the happy and healthy social integration of the ADHD child with their peers.

Preparing the Teacher. Although teachers can expect at least one student in every classroom to have ADHD, there is currently little training that prepares them for managing these children. The teacher should be prepared for the certain behaviors in the child with ADHD:

Students with ADHD are often demanding, talkative, and highly visible.
Inattention is a major factor in low academic performance. It causes them to frequently forget homework or miss assignments. Children with ADHD often require frequent reminders or visual cues (such as posters) for rules and regulations. Having the child sit in the front of the classroom may be helpful for both increasing attention and reducing noisy activity.
Lack of fine motor control makes taking notes very difficult, and handwriting is often poor. Using a typewriter or computer can compensate for this. One useful skill that has helped some children is learning to type at an early age, around the third or fourth grade.
Rote memorization and math computation, which require following a set of ordered steps, are often difficult. (Children with ADHD may do better with math concepts.)
Many children with ADHD respond well to school tasks that are rapid, intense, novel, or of short duration (such as spelling bees or competitive educational games), but they almost always have problems with long-term projects where there is no direct supervision.

The Role of the Parent in the School Setting. The parent can help the child by talking to the teacher before the school year starts about their child's situation:

The first priority for the parent is to develop a positive, not adversarial, relationship with the child's teacher.
The parent must acknowledge the teacher's situation, for the teacher must deal not only with the ADHD child's behavior but also with the needs of all the other children.
Frequent brief and sympathetic conversations with the teacher can be helpful and can lead to coordination of efforts, particularly if they provide reciprocal information about progress or setbacks.
Finding a tutor to help after school may be helpful. It is not clear, however, if tutoring offers significant benefits for children whose academic problems stem from inattention unless it is structured specifically to address this problem.

Special Education Programs. The Individuals with Disabilities Education Act (IDEA) requires the school to identify and evaluate children who may need help and to provide special services. However, parents sometimes report pressure by the school to put their children on medication or force them into special classrooms without clear educational justification. The schools, in these cases, may be acting illegally.

High-quality special education can be extremely helpful in improving learning and developing a child's sense of self worth. Many families, however, may not have appropriate programs available for them. Programs vary widely in their ability to provide quality education. Parents must be aware of certain limitations and problems with special education:

Special education programs within the normal school setting often increase the child's feelings of social alienation.
If the educational strategy focuses only on abnormal behavior, it will fail to take advantage of the creative, competitive, and dynamic energy that often accompanies ADHD behavior.
There is no federally funded special education category specifically targeted to ADHD.

If, in fact, ADHD is as common as studies are indicating, the best approach may be to treat the syndrome as a variant of the norm and train teachers to manage these children within the context of a normal classroom.

Special programs are also required under the Rehabilitation Act and by the Americans with Disabilities Act (ADA) for students at institutions of higher learning. It is the student's responsibility, however, to inform the administration at their college or university that they need such services. Unfortunately, many college students are reluctant to do this, although such programs can provide important and beneficial assistance in improving their academic performance.

Other Treatments

A number of diets have been suggested for people with ADHD. Several well-conducted studies have failed to support dietary effects of sugar and food additives on behavior, except possibly in a very small percentage of children. Still various studies have reported behavioral improvement with diets that restrict possible allergens in the diet. Parents may want to discuss with their doctor implementing an elimination diet of certain foods that would not be harmful and that might help.

Food Allergies. Evidence suggests that children with behavioral difficulties may be sensitive to certain chemicals in foods. Studies vary widely, however, on how many cases of ADHD may be associated with sensitivities or allergies to food chemicals or additives, with results ranging widely from 5 - 62%. Among the suspected additives and foods that parents and studies report as inciting behavioral changes are the following:

Any artificial colorings (particularly yellow, red, or green)
Other chemical additives -- for example, BHT or BHA
Milk
Chocolate
Eggs
Wheat
Foods containing salicylates, including all berries, chili powder, apples and cider, cloves, grapes, oranges, peaches, peppers (bell & chili), plums, prunes, tomatoes

In one small study, 62% of children who were given only rice, turkey, pears, and lettuce to eat for 2 weeks experienced at least a 50% improvement in symptoms. Nevertheless, about a quarter of the children pulled out because they could not stick with the diet or they became ill.

Feingold Diet. The most well-known diet for ADHD is the Feingold diet, a salicylate- and additive-free diet, which requires rigorous vigilance over a child's eating habits. This diet also prohibits aspirin, which contains salicylates. Some parents report great success with this diet, although it may be difficult to impose. One study that reported the diets efficacy suggested that it might not provide enough nutritive value, although the diet provides a wide range of healthy foods to select from. It is certainly wise, in any case, to avoid food with artificial colors and flavors and to provide a healthy balance of fresh, natural foods.

Essential Fatty Acids. Omega-3 fatty acids, found in fatty fish and certain vegetable oils, are important for normal brain function and may have some benefits for people with ADHD. It is not clear if supplements of fatty acid compounds, such as docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA), provide any advantages.

Zinc. Zinc is important for the metabolism of certain neurotransmitters that play a role in ADHD, and deficiencies have been associated with some cases of ADHD. Long-term use of zinc, however, can cause anemia and other side effects in people without deficiencies and it has no effect on ADHD in these patients. In any case, testing for trace minerals, such as zinc, is not standard procedure when evaluating children suspected to have ADHD.

Sugar. Although parents often blame sugar for causing children to become impulsive or hyperactive, a number of studies strongly indicate that sugar plays no role in hyperactivity. One study reported, in fact, that ADHD children had fewer problems after a high-carbohydrate breakfast than after a high-protein one. Another reported that children actually moved more slowly after a high-sugar meal, suggesting the carbohydrates may have a sedative effect. (Still, it's probably always wise for any child to cut down on sugar.)

Techniques that use biologic or auditory feedback are proving to be effective tools for increasing children's attention -- a primary factor in low academic performance.

Neurofeedback. Neurofeedback is an approach that uses electronic devices to help the child control their own brain wave activity. Electrodes are pasted to the child's head and pick up signals from the brain. The child watches images, such as moving graphs, on a computer monitor that reflect the child's brain wave activity. Children are then taught certain high-level mental activities at the point when feedback information on the screen indicates that they are fully concentrating. Children usually attend forty 50-minute sessions, usually twice a week. Small studies have reported significant improvement in inattention, impulsivity, and response time.

Interactive Metronome and Musical Therapy. Interactive metronome uses feedback from sound to improve attention, motor control, and certain academic skills. In this technique study, children wear headphones and sensors on their hands and feet. They perform a number of exercises to a rhythmic computer-beat. Training sessions are completed in 3 - 5 weeks. Some small studies have reported improvement in attention, motor control, language processing, and behavior. (In support of this, some parents report that learning a musical instrument helped their children significantly.)

Procedures and Non-Drug Therapies. A number of alternative approaches are used for children and adults with mild ADHD symptoms. For example, daily massage therapy may help people with ADHD feel happier, fidget less, be less hyperactive, and focus on tasks. Other alternative approaches that may be helpful include relaxation training, meditation, and music therapy. Based on existing evidence, these treatments may be helpful for symptom management but are not proven to benefit the underlying disorder.

Natural Remedies. A number of parents resort to alternative remedies as an alternative to psychostimulants and other drugs. Small trials have found some herbs and supplements -- such as oral flower essence, ginkgo biloba, panax ginseng, melatonin, and pine bark extract (Pycnogenol) --may possibly have benefits for ADHD. Based on existing evidence, however, none can be recommended, particularly for children.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for attention-deficit disorders:

Melatonin. High doses of melatonin have been associated with an increased risk for seizures in children with existing neurologic disorders.
Gingko. The risk for side effects from gingko appear to be low, but there is an increased risk for bleeding and interaction with anti-clotting medications at high doses.
Ginseng. There have been contaminated forms of imported ginseng. Ginseng also has been associated with low blood sugar and a higher risk for bleeding. In addition, a great number of ginseng products have been found to contain little or no ginseng.

Resources

www.aap.org -- American Academy of Pediatrics
www.nimh.nih.gov -- National Institute of Mental Health
www.chadd.org -- Children and Adults with Attention-Deficit Disorder
www.add.org -- Attention Deficit Disorder Association
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- American Psychiatric Association
www.parentsmedguide.org -- Medication Guide for Treating ADHD
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.nichcy.org -- National Dissemination Center for Children with Disabilities
www.ncld.org -- National Center for Learning Disabilities
www.ldaamerica.org -- Learning Disabilities Association of America

References

Braun JM, Kahn RS, Froehlich T, Auinger P, Lanphear BP. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children. Environ Health Perspect. 2006 Dec;114(12):1904-9.

Heinrich H, Gevensleben H, Strehl U. Annotation: neurofeedback - train your brain to train behaviour. J Child Psychol Psychiatry. 2007 Jan;48(1):3-16.

Jensen PS, Arnold LE, Swanson JM, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(:989-1002.

Nigg JT, Breslau N. Prenatal smoking exposure, low birth weight, and disruptive behavior disorders. J Am Acad Child Adolesc Psychiatry. 2007 Mar;46(3):362-9.

Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jul;46(7):894-921.

Steiner H, Remsing L; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with oppositional defiant disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):126-41.

Swanson JM, Elliott GR, Greenhill LL, et al. Effects of stimulant medication on growth rates across 3 years in the MTA follow-up. J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(:1015-27.

Valera EM, Faraone SV, Murray KE, Seidman LJ. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Psychiatry. 2007 Jun 15;61(12):1361-9. Epub 2006 Sep 1.

Wilens TE, Upadhyaya HP. Impact of substance use disorder on ADHD and its treatment. J Clin Psychiatry. 2007 Aug;68(:e20.

Williams JH, Ross L. Consequences of prenatal toxin exposure for mental health in children and adolescents: a systematic review. Eur Child Adolesc Psychiatry. 2007 Jun;16(4):243-53. Epub 2007 Jan 2.

Review Date:
12/27/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Depression

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications of Depression...
Diagnosis
Treatment
Antidepressants and Drug Tr...
Psychotherapy
Other Treatments
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved the atypical antipsychotic drug aripiprazole (Abilify) for treatment of major depression in adults. Aripiprazole is used for treatment of schizophrenia and bipolar disorder. For depression, it is used in combination with antidepressant drug therapy. Researchers are also investigating other atypical antipsychotics for major depression treatment.

Antidepressants and Suicide Risk

In 2007, the FDA proposed adding new information to antidepressant warning labels concerning the increased risk for suicidal thinking and behavior among young adults ages 18 - 24 during the initial months of drug therapy.
The benefits of antidepressants for children and adolescents outweigh their potential risks, suggests a 2007 study in the Journal of the American Medical Association.

Antidepressants During Pregnancy

Most selective serotonin reuptake inhibitors (SSRIs) do not significantly increase the risk for birth defects when taken during early pregnancy, indicate several 2007 studies in the New England Journal of Medicine. However, some SSRIs -- such as paroxetine (Paxil) -- carry a higher risk than others. Researchers are still studying the overall safety of SSRIs during pregnancy. Women with depression should discuss with their doctors all potential risks and benefits.

Introduction

Everyone experiences some unhappiness, often as a result of a change, either in the form of a setback or a loss, or simply, as Freud said, "everyday misery." The painful feelings that accompany these events are usually appropriate, necessary, and transitory, and can even present an opportunity for personal growth. However, when depression persists and impairs daily life, it may be an indication of a depressive disorder. Severity, duration, and the presence of other symptoms are the factors that distinguish normal sadness from a depressive disorder.

Depression has been alluded to by a variety of names in both medical and popular literature for thousands of years. Early English texts refer to "melancholia," which was for centuries the generic term for all emotional disorders.

Depression is now referred to as a mood disorder, and the primary subtypes are major depression, dysthymia (chronic and usually milder depression), and atypical depression. Other important forms of depression are premenstrual dysphoric disorder (PDD or PMDD) and seasonal affective disorder (SAD).

Depression is defined as a mood disorder, and there are several subtypes. Bipolar disorder, also known as manic-depressive illness, is considered in a separate category.

The other major mood disorder is bipolar disorder, or manic-depressive illness, which is characterized by periods of depression alternating with episodes of excessive energy and activity. Bipolar disorder is not discussed in this report. [For more information, see In-Depth Report #66: Bipolar disorder.]

In major, or acute, depression, at least five of the symptoms listed below must occur for a period of at least 2 weeks, and they must represent a change from previous behavior or mood. Depressed mood or loss of interest must be present. Symptoms include:

1. Depressed mood on most days for most of each day -- irritability may be prominent in children and adolescents

2. Total or very noticeable loss of pleasure most of the time

3. Significant increases or decreases in appetite, weight, or both

4. Sleep disorders, either insomnia or excessive sleepiness, nearly every day

5. Feelings of agitation or a sense of intense slowness

6. Loss of energy and a daily sense of tiredness

7. Sense of guilt or worthlessness nearly all the time

8. Inability to concentrate occurring nearly every day

9. Recurrent thoughts of death or suicide

In addition, other criteria must be met:

The symptoms listed above do not follow or accompany manic episodes (such as in bipolar disorder or other disorders).
They impair important normal functions (such as work or personal relationships).
They are not caused by drugs, alcohol, or other substances.
They are not caused by normal grief.

A long-term study found that episodes of major depression usually last about 20 weeks. Between 30 - 40% of depressed patients experience sudden attacks of anger that they describe as uncharacteristic and inappropriate.

Click the icon to see an image of childhood depression.

Dysthymia, or chronic depression, afflicts 3 - 6% of the general population and is characterized by many of the same symptoms that occur in major depression. Symptoms of dysthymia are less intense and last much longer, at least 2 years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities. Possibly because of the duration of the symptoms, patients who suffer from chronic minor depression do not exhibit marked changes in mood or in daily functioning, although they have low energy, a general negativity, and a sense of dissatisfaction and hopelessness.

Double Depression. Often, symptoms become more severe over time. In one long-term study, nearly all patients with dysthymia suffered at least one episode of major depression superimposed over chronic depression (sometimes called double depression) at some time in their life. Some experts believe that such double depression should be considered as part of the natural course of dysthymic disorder. Women may be more susceptible to double depression. In one study, more than one-third of those who recovered from dysthymia relapsed within 5 years.

About a third of patients with depression have atypical depression. Symptoms include overeating and oversleeping. Such patients tend to have a feeling of being weighed down and react strongly to rejection. It tends to occur more in women, unmarried people, and those with other emotional disorders, such as anxiety or substance abuse. It also may impair functioning more severely than ordinary depression does.

Seasonal affective disorder (SAD) is characterized by annual episodes of depression during fall or winter that remit in the spring or summer. Other SAD symptoms include fatigue and a tendency to overeat (particularly carbohydrates) and oversleep in winter. A minority of individuals with SAD has the more common depressive symptoms of undereating and being sleepless. SAD tends to last about 5 months in those who live in the northern part of the U.S.

Seasonal changes affect many people's moods, regardless of gender and whether or not they have SAD. Simply being mildly depressed during the winter does not mean that one has SAD. Living in a northern country with long winter nights does not guarantee a higher risk for depression. Changes in light may not be the only contributor to SAD.

Causes

The causes of depression are not fully known. Most likely a combination of genetic, biologic, and environmental factors are at work.

Because depression runs in families, and has a strong genetic component, compelling evidence suggests that depression is a biologic phenomenon. Data from family, twin, adoption, and genetic studies have confirmed this. Studies have found that first-degree relatives of patients with depression are two to six times more likely to develop the problem than individuals without a family history.

Evidence supports the theory that depression has a biologic basis. The basic biologic causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain). These neurotransmitters regulate mood and associated behaviors. Scientists hope that by identifying the gene mutations that code the regulation of these neurotransmitters, they may eventually be able to predict which patients are most likely to respond to specific antidepressant drugs.

Serotonin. Perhaps the most important neurotransmitter in depression is serotonin. Among other functions, it is important for feelings of well-being. Imbalances in the brain’s serotonin levels can trigger depression and other mood disorders.
Other Neurotransmitters. Other neurotransmitters possibly involved in depression include acetylcholine and catecholamines, a group of neurotransmitters that consists of dopamine, norepinephrine, and epinephrine (also called adrenaline). Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety. Increased CRF concentrations appear to interact with serotonin and have been detected in patients with either depression or anxiety.

Endocrine glands release hormones into the bloodstream that are transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary gland to secrete hormones that determine the pace of chemical activity in the body. The more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity.

The degree to which these chemical messengers are disturbed is determined by other factors, such as light, structural abnormalities in the brain, sleep disorders, or genetic susceptibility. For example, researchers have identified a defect in the gene known as SERT, which regulates serotonin and has been linked to depression.

Reproductive Hormones. In women, the female hormones estrogen and progesterone most likely play a role in depression.

Women, regardless of nationality or socioeconomic level, have significantly higher rates of depression than men. The causes of such higher rates appear to be a mix of biologic and cultural factors.

Social and Economic Factors. The role that work, marriage, and children play in a woman's depression is complex. Many women feel that they must be everything to everyone and at the same time feel as if they are no one at all. Such a self-image is common and should be strongly considered as a major contributor to depression in many women, particularly those who work and have small children.

Hormonal Fluctuations and Life Stages. Extreme hormonal shifts can trigger emotional swings in all women. The role of hormones in depression is not clear, however, and is mostly based on observations of depression during specific stages in female development. Female hormones undoubtedly play some role in premenstrual dysphoria, postpartum depression, and SAD. These forms of depression recede or stop after menopause.

Early Puberty. Girls who go through puberty early (reaching the midpoint at 11 years or younger) are more likely to experience depression during adolescence than girls who mature later.

Premenopause. Premenopausal women ages 20 - 45 are most susceptible to depression, with 22% of this age group reporting symptoms of major depression. Specifically, premenstrual dysphoric disorder (severe depression before a period) affects an estimated 3 - 8% of women during their reproductive years. [For more information, see In-Depth Report # 79: Premenstrual syndrome.]

Perimenopause. Depression often occurs around menopause (the perimenopausal period), when, in addition to hormonal changes, other factors such as cultural pressures favoring young women, sudden recognition of aging, and sleeplessness are involved.

Postmenopause. Once women pass into the postmenopausal period, studies suggest that average depression scores are nearly as low as those in premenopausal women. In fact, many women report that after menopause, previous bouts of depression, particularly when caused by seasonal changes or premenopausal syndrome, recede or stop completely.

Premenstrual Dysphoric Disorder. The syndrome of severe depression, irritability, and tension before menstruation is known as premenstrual dysphoric disorder (PDD or PMDD), also called late-luteal dysphoric disorder. It affects an estimated 3 - 8% of women in their reproductive years. A diagnosis of PDD depends on having five or more standard symptoms of major depression that occur during most menstrual cycles, with symptoms worsening a week or so before the menstrual period and resolving afterward. PMDD has features of both anxiety and depression disorders, although experts increasingly believe it is a distinct disorder with specific biochemical abnormalities. [For more information, see In-Depth Report #79: Premenstrual disorder.]

Depression During Pregnancy. Pregnancy is certainly an occasion of great celebration for most women most of the time. However, emotions during that time are not always straightforward, and depression is a common (although most often a temporary) companion. Prenatal depression can affect a mother's sleep, physical activity, adherence to care, and appetite.

Miscarriage. Miscarriage poses a very high risk for depression, particularly in the first month after the loss. Older women with no previous successful pregnancies and those with a history of depression are at particular risk during this time. (Despite some concern that depression increases the risk for miscarriage in the first place, there is no evidence to support this.)

Postpartum Depression. Most new mothers experience weeping, irritability, and confusion for a few days following childbirth. Such symptoms, known as the "baby blues," are not considered signs of postpartum depression unless they persist in severe form nearly every day for more than 1 - 2 weeks.

Women are most likely to develop postpartum depression and other mental disorders in the first 3 months following delivery. (The risk is highest for first-time mothers, especially in the 10 - 19 days after delivery.) Other studies have reported that 8 - 20% of women have diagnosable postpartum depression within that 3-month period. In one study, 5% of these women had suicidal thoughts.

Studies have not found any association between a higher risk for postpartum depression in women and the following:

Educational level
Gender of the child
Whether or not the woman breast-feeds
Whether or not the pregnancy was planned
Whether the delivery was vaginal or cesarean

The rapid decline of reproductive hormones that accompany childbirth is likely to play the major role in postpartum depression in susceptible women. Fluctuating thyroid hormones can also contribute to depression. Studies suggest that women who are more sensitive to hormone fluctuations are at greater risk for postpartum depression if they have one or more of the following conditions:

A history of prior depressive episodes
A family history of mood disorders
Stressful life events (such as being a new mother and having an infant with medical problems)
Lack of social support or feeling as if it is lacking

Depressed children often suffer in silence, and depression may be evident only from reports of problems in school. It is also often difficult for adults to believe that children can be chronically depressed. Symptoms for depression in children often differ from those in adults and may include the following:

An inability to enjoy favorite activities
Persistent sadness
Increased irritability
Complaints of physical problems, such as headaches and stomachaches
Poor performance in school
Persistent boredom
Low energy
Poor concentration
Changes in eating and/or sleeping patterns
A greater tendency to bully others -- anxious children are more often bullied.

Risk Factors for Depression in Children and Adolescents. Depression can occur in children of all ages, including preschoolers, although adolescents have the highest risk (about 20%). Risk factors for depression in young people include having parents, particularly mothers with depression. Early negative experiences and exposure to stress, neglect, or abuse also pose a risk for depression. Sometimes depression develops after a physical illness. In adolescents, feeling alienated from parents is a strong predictor for depression.

Outlook for Future Emotional Problems. Adolescents who have depression are at significantly higher risk for substance abuse, recurring depression, and other emotional problems (such as bipolar disorder) in adulthood.

Risk for Suicide in Adolescents. Suicide is the third most common cause of death among adolescents, and is one of the most devastating events than can happen to a family. Suicide is most commonly associated with depression in young people but it is also linked with anxiety, psychosis, substance abuse, or impulsivity. More girls attempt suicide but more boys succeed, most often because they choose guns or violent methods while girls tend to overdose, which is more treatable. Nevertheless, attempts are major risk factors for a later suicide. Any expression of suicidal intent should be treated very seriously.

The following are danger signs in young people:

Withdrawal from friends
Sudden decrease in school performance
Loss of interest in activities that were previously pleasurable
Unusual irritability
Unusual changes in sleep or eating habits

Risk factors for suicide include a history of neglect or abuse, history of deliberate self-harm, a family member who committed suicide (nearly always one who shared a common mood disorder), access to firearms, and living in communities where there have been recent outbreaks of suicide in young people. A romantic break-up is often the trigger for a suicidal attempt in teenagers. Feeling connected with parents and family protected young people with depression in one study, regardless of gender or ethnicity.

Adolescents may fail to seek help for suicidal thoughts for the following reasons:

They believe nothing would help
They are reluctant to tell anyone they had problems
They think it is a sign of weakness to seek help
They do not know where to go

Parents should not hesitate to seek professional help for their children if they suspect they are thinking about killing themselves. This is a medical emergency and requires immediate treatment.

Behavioral therapies and antidepressants are promising treatments for preventing suicide but need study. There has been a decline in adolescent suicides over the past decade, which some experts attribute to the increased use of antidepressants in this population. However, recent evidence has indicated that antidepressants can also raise the risk for suicidality (suicidal thoughts and behavior) in some people. Children, adolescents, and young adults who are prescribed antidepressant medication should be carefully monitored by both their parents and doctor, especially during the first few months of treatment, for any worsening of depression symptoms or changes in behavior. [See Suicide Risk and Antidepressant Medications in Medication section.]

Although depression in the elderly is very common, the aging process itself is unlikely to be the cause in most cases. An Italian study, for example, indicated that the very old (people who lived beyond 90 years of age) were no more likely to be depressed than younger adults. (The rate was 10% in both groups.) Studies on the cause or extent of depression in the elderly are not clear.

The severity of depression in elderly patients is strongly associated with poor health and less ability to function. In one study of older adults undergoing rehabilitation, half of whom were depressed, as their function improved so did their mood.

Anyone who experiences cumulative negative life events, physical illness, the death of a loved one, impaired functioning, or loss of independence can become deeply depressed. The elderly are at highest risk for such events.

Diagnosing Depression in the Elderly. Because of the complex relationship between depression, drug interactions, and serious physical illness in the elderly, an accurate diagnosis in this group is important but not always straightforward. The characteristic symptoms of depression are not always present or readily apparent in older people:

Some older people may be aware of their depression but believe that nothing can be done about it.
Many elderly people who are depressed may report only physical symptoms (aches and pains) or other mood states (confusion, agitation, anxiety, and irritability) related to depression rather than depression itself.
Often they are unable or unwilling to express their feelings or are even unaware that they are depressed.
Their symptoms are often ignored or confused with other ailments common in the elderly, including Parkinson's or Alzheimer's disease, dementia, thyroid disorders, arthritis, stroke, cancer, heart disease, and other chronic conditions.
Depression is also a side effect of many drugs that are commonly prescribed for the elderly. It is often very difficult, then, to determine if the patient's depression is a psychologic reaction to the illness, caused by the disease itself, or completely independent from the medical condition. Both physical and emotional conditions should be considered in making a diagnosis in older people.

Many studies suggest strong associations between even mild depression and poorer quality of life as well as a shorter lifespan.

Risk for Suicide in the Elderly. Suicide in the elderly is the third-leading cause of death related to injury. Men account for 81% of these suicides, with divorced or widowed men at highest risk.

Effects of Depression on the Ability to Function. Even mild depressive symptoms in people aged 65 and above are associated with a higher risk of becoming disabled and having a lower chance of recovery.

Heart Disease and Heart Attacks. Depression increases the severity of a heart attack and may even impair a patient's response to medication for heart disease. Although people with heart disease may certainly become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a true risk factor for heart disease as well as its increased severity. A number of studies indicate that depression has biologic effects on the heart, including a higher risk for blood clotting, changes in heart rate, and impaired blood flow to the heart (particularly in response to mental stress). The more severe the depression, the more dangerous to the health, although even mild depression, including feelings of hopelessness, experienced over many years, may harm the heart, even in people with no early signs of heart disease.

Mental Decline. Depression in the elderly is associated with a decline in mental functioning, regardless of the presence of dementia. Depression may be a predictor or even a cause of Alzheimer's disease. Brain scans in the elderly, for example, have reported greater atrophy in the brains of depressed individuals than in those of nondepressed ones.

Risk Factors

According to a major surveys, more than 13% of Americans have major depression disorder over the course of their lifetimes. Furthermore, an estimated 18 million Americans experience major depression each year. Depression is second only to high blood pressure as a chronic condition encountered by primary care doctors. Depression is an illness that can afflict anyone, regardless of age, race, class, or gender. A third of all depressed people consider suicide, and 9% attempt it.

Depression in Women. At any given time, 5 - 9% of women are depressed, compared to 1 - 3% of men. In one study, nearly half of all women surveyed had experienced depression at some point in their lives and over half of those who suffered from it had sought treatment. Women are also more apt to have multiple types of depression (dysthymia and major depression). [For more information, see Depression in Women.]

Depression in Men. Depression is not rare in men. In fact, prepubescent boys are more likely than girls of the same age to be depressed. Older men are also at much higher risk for suicide and, as with women, they are at risk for health complications of depression. Some evidence suggests that men are more apt than women to mask their depression by using alcohol, which may result in a lower reported (but not actual) incidence of depression in men. Some experts suggest that men with depression might be identified with the following indicators:

Low tolerance to stress
Behaviors such as "acting out" and being impulsive
A history of alcohol or substance abuse
A family history of depression, alcohol abuse, or suicide

Depression is less reported in the male population, but this may be caused by male tendency to mask emotional disorders with behavior such as alcohol abuse.

Depression in Children and Adolescents. Children ages 12 - 16 are at high risk for depression. Studies suggest that 3 – 5% of children and adolescents suffer from depression, and 10 – 15% have some depressive symptoms. Depression before puberty is more likely to occur in boys and after puberty in girls.

Depression in Adults. Surveys indicate that depression usually begins around the age of 30, although people do not generally seek treatment until they are about 33 years old. Statistics also suggest that depression is becoming more common among middle-aged people ages 45 - 64. According to a 2005 survey, middle-aged adults have the highest lifetime risk for depression.

Depression in the Elderly. Studies suggest that 5 – 14% of the elderly population suffer from some form of depression. In addition, the elderly are highly vulnerable to suicide. Elderly people comprise 13% of the U.S. population but account for 18% of all suicide deaths.

The role of society and economics has specific implications for women. [See Depression in Women.] Being in a low socioeconomic group is a major risk factor for depression in anyone. Money, of course, allows greater access to good medical care, but this factor does not fully explain the higher rates of depression in impoverished people. People at any income level are likely to be depressed if they have poor health and are socially isolated. Some studies suggest that Western cultural attitudes that link income to social status may play a significant role in the connection between poverty and depression:

In one British study, actual poverty or unemployment increased the duration of any existing depression, but it did not appear to play any important causal role. Feelings of financial insecurity, however, both caused and prolonged depression.
Another study reported that Mexican adults who immigrated to America had half the psychiatric illnesses as did Mexican-Americans born in the U.S., regardless of their income. But the longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional influences of Mexican culture and social ties appeared to protect newly arrived immigrants from mental illness, even when they were poor. Eventually, however, the consequences of Americanization added to poverty and led to feelings of alienation and inferiority.

Depression in family members increases the risk for depression in other family members. Studies report that depression for even 1 - 2 months in a mother increases the risk for depression in her children. The more severe the maternal depression, the higher the risk for depression in the children. In a perpetuating cycle, being depressed as a child increases the risk for depression during adulthood. In such cases, genetic or environmental factors or both may be responsible. Spouses of partners with depression are themselves at higher risk for depression.

Patients who have had serious bouts of depression usually cite a stressful life event as the precipitating factor for their illness. Adverse events during childhood pose a higher risk for depression in adulthood. In one study, parental divorce, physical abuse, and frightening experiences were particularly associated with onset of depression in adulthood. Only divorce was associated with recurrence, however.

Adverse events in adulthood also trigger depression. Losing a spouse through divorce or death is a major risk factor for depression in anyone. In fact, recent loss of a loved one is the most frequently reported precipitant of acute depression. All major (and even minor) losses, however, cause grief reactions. People who develop acute or chronic depression after a loss may have predisposing factors, including genetic or biologic ones, which make them more vulnerable. The existence or absence of a strong social network of family, friends, or both also has a major positive or negative effect, respectively, on recovery. Most people are able to cope with the emotional pain and eventually move beyond it without becoming chronically depressed. [See Ruling out Grief and Loneliness in the diagnosis section of this report.]

Traumatic events such as abuse or even natural disasters can cause severe immediate or delayed depression from which recovery takes a long time.

Severe or Chronic Medical Conditions. Any chronic or serious illness that is life-threatening or out of a person's control can lead to depression.

Thyroid Disease. Hypothyroidism (a condition caused when the thyroid gland does not produce enough hormone) can cause depression. However, hypothyroidism may also be misdiagnosed as depression and go undetected.

Chronic Pain Conditions. Studies have reported a strong association between depression and headaches, including chronic tension-type and migraine. Some experts believe that a syndrome of migraine headaches (and also possibly tension-type), anxiety, and depression is caused by common factors, such as abnormalities in chemical messengers, particularly dopamine or serotonin. Fibromyalgia and other chronic pain syndromes are also associated with depression.

Stroke and Other Neurological Conditions. Having a stroke increases the risk of developing depression. Also, patients with Parkinson's disease, spinal cord injuries, and other similar problems that impair movement or thinking are associated with depression.

Heart Failure. Patients with heart failure or patients who have suffered a heart attack may also suffer from depression.

A number of drugs taken for chronic problems cause depression. Among them are pain relievers for arthritis, cholesterol-lowering drugs, medications for high blood pressure and heart problems, and bronchodilators used for asthma and other lung disorders.

There is a significant association between cigarette smoking and a susceptibility to depression. People who are prone to depression face a 25% chance of becoming depressed when they quit smoking, and this increased risk persists for at least 6 months. What's more, depressed smokers are unlikely to stop smoking. Only about 6% remain smoke-free after a year. Smokers with a history of depression are not encouraged to continue smoking, but rather to keep a close watch on recurrence of depressive symptoms if they do stop smoking. The antidepressant bupropion (Wellbutrin), which is approved for helping people quit smoking (marketed under the name Zyban), is proving to be very useful in helping smokers to quit.

Chronic depression is a frequent companion to anxiety disorders. In one study, up to 96% of patients with depressive disorders experienced concurrent anxiety. More than two-thirds of people with obsessive-compulsive disorder, a common anxiety disorder, also suffer from depression.

Some evidence suggests that certain personality styles, which include an intense need for close relationships and concern for disapproval or need for control, pose a high risk for depression, particularly after an adverse life event. In line with these findings, the following specific personality disorders have been associated not only to a first episode of depression, but also to relapses:

A person with borderline personality disorder acts impulsively and has a poor self-image and unstable relationships. In one study, patients with borderline personality disorder and major depression were more likely than those with either condition alone to plan and attempt suicide.
An individual with an avoidant personality avoids strangers and unfamiliar situations.

(Personality disorders, as opposed to emotional disorders, are those with abnormal behavioral patterns rather than abnormal emotions.)

Sleep abnormalities are an integral part of depressive disorders, with more than 90% of depressed patients experiencing insomnia. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of emotional disorders. Some experts think that some psychiatric disorders can be prevented by early recognition and treatment of insomnia.

Seasonal affective disorder (SAD) affects about one in 20 adults. About 80% of people who suffer from SAD are women. People who live in the north are more apt to experience SAD than people who live in southern latitudes.

Complications of Depression

Depression is often chronic, with episodes of recurrence and improvement. About one-third of patients with a single episode of major depression will have another episode within 1 year after discontinuing treatment, and more than 50% will have a recurrence at some point in their lives. Depression is more likely to recur if the first episode was severe or prolonged, or if there have been recurrences. To date, even newer antidepressants have failed to achieve permanent remission in most patients with major depression, although the standard medications are very effective in treating and preventing acute episodes.

About 90% of suicides are due to treatable disorders, most commonly depression or substance abuse. People with depression have up to a 15% risk for suicide, with the highest risk in patients who are hospitalized for depression. Some studies indicate that atypical depression poses a higher risk for suicide than typical depression and that dysthymia may pose a higher risk than episodic major depressive disorder. Depressed men are more likely to commit suicide than depressed women. Around the world, suicide is most common in men older than 60. Suicidal preoccupation or threats of suicide should always be treated seriously in anyone, however. [See Depression in the Elderly or Depression in Children in this report.]

Major depression in the elderly or in people with serious illness seems to reduce their survival rates, even independently of any accompanying illness. Decreased physical activity and social involvement certainly play a role in the association between depression and illness severity.

Effect on Heart Disease and Other Age-Related Problems. Many studies report strong associations between depression and a worse and even shorter old age. Depression is also associated with mental decline in older people.

Studies are now showing that depression may contribute to poor outcomes for patients with heart disease.

Obesity. Both obesity and depression are increasing in Americans. Adolescents who are depressed have a high risk for obesity. Conversely, obese people are about 25% more likely than non-obese people to develop depression or other mood disorders. The conditions may have common risk factors. For example, being in a lower social and economic group increases the risk for both obesity and depression. Low physical activity may also be a common factor.

Increasing Sensations of Pain. Depression coincides with increased pain in people with conditions such as those arthritis or fibromyalgia.

Cancer. The relationship between depression and cancer has been explored for years with only a few clear-cut associations. Certainly depression and anxiety can have a profound impact on quality of life in cancer patients.

Effects of Parental Depression on Children. Depression in parents can have profound effects on their children and may increase the risk for childhood depression.

Effects on Marriage. In one survey, nearly half of people who suffered from psychiatric disorders before or during their first marriage were divorced, compared to a divorce rate of 36% in those who never suffered from emotional disorders. Spouses of partners with depression are themselves at higher risk for depression.

Effect on Work. Depression is well-known to adversely affect a person's work life. It significantly increases the risk for unemployment and lower income. Nearly half of the nation's excess lost productive time (in most cases because of reduced performance at work) may be a result of depression. Workers with depression also lose significantly more time due to ill health than non-depressed workers. Such lost time is estimated to cost the country billions of dollars each year.

Alcohol and Drug Abuse. About 14% of people with major depression also have an alcohol use disorder and 5% have drug abuse problems. Studies on the connections between alcohol dependence and depression have still not resolved whether one causes the other or if they both share some common biologic cause.

Smoking. Depression is a well-known risk factor for smoking, and 26% of people with major depression are nicotine dependent. Nicotine may stimulate receptors in the brain that improve mood in certain people with genetically induced depression.

Diagnosis

Most people who are depressed do not seek psychiatric help and must rely on their family doctor. Unfortunately, it is often difficult for a primary care doctor to recognize the problem if the patient does not bring it up directly.

Patients themselves may be unable to sense or admit their own depression. In one study, although 21% of patients who visited their family doctors were depressed, only 1% described their problem as depression.

Depression can also be confused with other medical illnesses. Weight loss and fatigue, for example, accompany many conditions, some serious, but they can also occur with depression.

Although not all patients who visit their doctor should be screened for depression, individuals who have certain factors might ask their doctor if they should be screened for depression. For example, the following people may be at higher risk and therefore warrant a screening test:

People with a family or personal history of depression
Patients with multiple medical problems
Patients with physical symptoms that have no clear medical cause
Patients with chronic pain
Individuals who visit their doctor more frequently than expected

A mental health specialist, such as a psychiatrist, social worker, or psychologist, is the best source for a diagnosis of depression. Such health professionals may administer a screening test such as the Beck Depression Inventory or the Hamilton Rating Scale, both of which consist of about 20 questions that assess the individual for depression. Studies are finding that even computerized phone interviews are valuable as screening tools for depression. However, most mental health professionals generally diagnose depression based on symptoms and other criteria.

Specific ethnic groups may present different symptoms of depression. People from non-Western countries are more apt to report physical symptoms (such as headache, constipation, weakness, or back pain) related to the depression, rather than mood-related symptoms.

Grief. The symptoms of grief (bereavement) and depression have much in common; indeed, it may be difficult to separate the two. Grief, however, is considered to be a healthy and important emotional response for dealing with loss, and it generally follows a characteristic path:

Grief normally has a limited duration. In people without any co-existing emotional disorder, bereavement usually lasts between 3 - 6 months.
The grieving person typically endures a succession of emotions that include shock and denial, loneliness, despair, social alienation, and anger.
The recovery period following this process, during which the individual becomes re-involved with life, takes about the same amount of time as the bereavement cycle.

If the grief is still severe after this period, however, it may affect a person's health or increase the risk for on-going depression. Some experts suggest that such a severe persistent grieving state be categorized as a separate psychologic diagnosis, termed complicated grief disorder, which would be related to post-traumatic stress syndrome and require special treatment.

Loneliness. Like grief, loneliness is a condition that may often be mistaken for depression. In fact, while loneliness and depression often go hand in hand, some researchers believe that some people with loneliness may be effectively treated for depression. Of course, every person feels loneliness now and then. Debilitating loneliness, however, is often characterized by misery, a feeling of hollowness, unrealistic expectations for one's life, and feeling removed from others. Shy people may be more prone to loneliness. Psychotherapy of various kinds may help people address and allay loneliness.

Treatment

Depression is a treatable illness, with many therapeutic options available. Increasingly, professionals are viewing major depression as a chronic illness (the condition nearly always returns when treatment is stopped). Therefore, medical intervention and help must be ongoing.

Patients with chronic depression have a number of options, including psychotherapy, antidepressants, or both. In general, the treatment choice depends on the degree and type of depression and other accompanying conditions. It also may depend on age, pregnancy status, or other individual factors.

Unfortunately, many Americans with major depression receive either inadequate treatment or no treatment at all. Reasons may include treatment by providers who may not have sufficient information or training on dosages or specific drugs that would be best suited for individual cases, lack of recognition of depression symptoms by providers, poor access to health care services, lack of health insurance, and poor compliance with medications.

Patients with Major Depression. Numerous studies support a combination of cognitive behavioral therapy (CBT) plus antidepressants, typically a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Although some people may feel better after taking antidepressants for a few weeks, most people need to take medication for at least 6 - 12 months to ensure a full response. Research indicates that patients respond better to medications when drug therapy is combined with CBT. Exercise is also important in helping relieve depressive symptoms.

For patients who are not helped by SSRIs or SNRIs, other types of antidepressants are available. Sometimes an atypical antipsychotic drug may be given in combination with an antidepressant for patients with severe major depressive disorder.

Brain stimulation techniques, such as electroconvulsive therapy (ECT) and vagus nerve stimulation, are also options. In recent years, experimental procedures, such as repetitive transcranial magnetic stimulation, have also been found to help in some cases of treatment-resistant depression. Researchers are also investigating new types of drugs (such as ketamine), which may provide a rapid, if temporary, improvement for these patients. In general, the more treatment strategies that patients need, the less likely they are to recover completely from depression.

Patients with Minor Depression. Patients with minor depression (fewer than five symptoms that persist for fewer than 2 years) may respond well to watchful waiting to see if antidepressants are necessary. Some studies indicate that antidepressants do not work that well for mild depression. Counseling or cognitive behavioral therapy may be helpful, as is regular exercise.

Patients with Depression and Other Psychiatric Problems. Other psychiatric problems often coexist with depression. If patients also suffer from anxiety, treating the depression first often relieves both problems. More severe psychiatric problems, such as bipolar disorder or schizophrenia, require specialized treatments.

Patients with Depression and Medical Conditions. Depression can worsen many medical conditions and may even increase mortality rates from some disorders, such as heart attack and stroke. Depression, then, should be aggressively treated in anyone with a serious medical problem.

Patients with Depression and Substance Abuse Problems. Treating depression in patients who abuse alcohol or drugs is important and can sometimes help patients quit. However, absence from substance abuse is considered essential for adequate treatment of depression.

Most people with depression can be treated in an office setting by a psychiatrist or other therapist. Infrequently, the level of dysfunction may be serious enough to warrant hospitalization to provide protection from further deterioration or self-harm.

Health professionals who can prescribe antidepressants include:

Doctors, including psychiatrists
Some nurse clinicians

Although other mental health professionals cannot prescribe drugs, most therapists have arrangements with a psychiatrist for providing medications to their patients. In general, mental health professionals are categorized by their training:

Psychoanalysts tend to have a degree in psychiatry, psychology, or social work as well as several years of training at a psychoanalytic institute.
Psychologists have received a Ph.D, including an internship in a mental healthcare facility.
A clinical social worker has a master's degree and 2 years of supervised experience in mental health and human services.
Advanced-practice psychiatric nurses have a master's degree and can provide therapeutic services.

Tips for Selecting a Therapist:

Patients can locate a mental health professional in their area by asking their doctor for a referral or by contacting a mental health organization. [See Resources.]
The patient should describe problems briefly but specifically over the phone to any prospective therapist to get a sense of whether he or she will suit the patient's needs.
An advanced degree does not necessarily guarantee quality therapy. The patient's belief in their health care provider may be the most important component in recovery.
Patients should not be shy about considering a change in their therapist if they lack confidence in their current one.

Although a mother's depression during and after pregnancy can have serious effects on her child, researchers are still trying to determine the best methods for preventing and treating pregnancy-related depression.

The use of antidepressants during pregnancy is controversial, especially for women with major depression who regularly take antidepressant medication. Most doctors advise women to avoid, if possible, any medications during pregnancy and nursing. But, women with depression who stop taking antidepressants during pregnancy may be likely to have a relapse of depression. Women who are pregnant or thinking about becoming pregnant should not stop taking antidepressants without first talking to their doctors.

Some research suggests that certain serotonin reuptake inhibitors (SSRIs) may increase risks for the fetus. The strongest evidence concerns the SSRI paroxetine (Paxil), which can cause major birth defects -- including heart abnormalities -- if taken during the first trimester of pregnancy. In 2006, the American College of Obstetricians and Gynecologists recommended that doctors should not prescribe paroxetine to women who are pregnant or planning on becoming pregnant.

Other research indicates that first-trimester use of SSRIs may increase the risk for rare skull and neural tube defects. Venlafaxine (Effexor), a dual inhibitor antidepressant, has been associated with birth complications when taken during the last trimester. In addition, some studies have shown that babies may experience withdrawal symptoms if their mothers take SSRIs late in pregnancy. However, the overall evidence indicates that there is a very low overall risk for antidepressant-associated birth defects and problems. Still, women should discuss all potential risks with their doctors.

In terms of non-drug treatment of postpartum depression, a review of 15 clinical trials suggested that postpartum depression is best treated by intensive and individualized psychotherapy within a month after a woman gives birth. The researchers found that women are too busy in the weeks before birth to attend prenatal classes that focus on preventing postpartum depression.

Some experts recommend only psychotherapy or attention intervention for elderly patients with mild depression. In many older patients, a regular exercise program may be sufficient to improve mood. Ideally, elderly people with more serious depression should be treated with a combination of psychotherapy and antidepressants on an ongoing basis, even after their depressive symptoms are relieved.

The use of antidepressants in the elderly is problematic:

Tricyclics are as effective as, and less expensive than, SSRIs, but they have more side effects. Specifically, they pose a higher risk for adverse effects on the heart and possibly the lungs. (The older tricyclics, such as amitriptyline and imipramine, have other severe side effects in older adults.)
SSRIs have fewer side effects than tricyclics. However, SSRIs may not pose any lower risk for falls than the older tricyclic antidepressants. In addition, researchers are investigating whether SSRIs are associated with an increased rate of osteoporosis (“thin bones”) and fractures in older adults.

About 2% of American primary school-age children and 4 - 8% of adolescents suffer from depression. Studies suggest that when children or adolescents are treated, up to 80% recover. Still, 25 - 50% of these young people have a recurrence of depression within 2 years of their first episode of depression.

It is important to recognize that childhood depression differs from adult depression and that children may respond differently than adults to antidepressant medication. These variances are due to childhood brain development processes as well as age-related differences in drug metabolism. Children may experience medication side effects not seen in adults, and some antidepressants that are effective for adults may not work for children.

Mild-to-Moderate Depression. The pediatrician may want to monitor a child with mild depression for 6 - 8 weeks before deciding whether to prescribe psychotherapy, antidepressant medication, or a referral to a mental health professional. Once medication has been started, the doctor will decide if the dosage needs to be increased after another 6 - 8 weeks. Medication may need to be continued for 1 year after the symptoms have resolved, and the doctor should continue to monitor the child on a monthly basis for 6 months after full remission of depression. For psychotherapy, cognitive therapy may be the best approach for children and adolescents with depression. Some studies suggest that other types of psychotherapy, such as family therapy and supportive therapy, can also be very effective.

Severe Depression. The American Academy of Child and Adolescent Psychiatry recommends an SSRI antidepressant for children and adolescents with very severe depression that does not respond to psychotherapy. Tricyclic antidepressants do not tend to help adolescents and children and these drugs have many side effects. MAOIs are also not commonly prescribed.

Many SSRIs appear to be safe and effective, but at this time fluoxetine (Prozac) is the only one approved for children over age 7 and for adolescents. The FDA strongly advises against the use of specific SSRIs, such as paroxetine (Paxil), due to concerns about an increased risk for suicidal behavior as well as the lack of any evidence supporting the drug's efficacy in pediatric patients. On an encouraging note, a 2007 review in the Journal of the American Medical Association indicated that the overall benefits of antidepressants for children and adolescents appear to be much greater than the risks for suicidal behavior. Still, the study found that antidepressants have only modest benefits for major depressive disorder, which underlines the importance of adjunctive psychotherapy.

For optimal results, SSRIs should be combined with either cognitive-behavioral or interpersonal psychotherapies. A study of adolescents with depression reported that combination treatment with fluoxetine and cognitive behavioral therapy was more effective than either treatment alone.

Due to potential suicide risks, children and adolescents should be monitored regularly during the initial months of antidepressant treatment. [For more detailed information, see Suicide Risk and Antidepressant Medications.]

Antidepressants and Drug Treatment Guidelines

Major classes of antidepressants include:

Selective serotonin-reuptake inhibitors (SSRIs). These have become the standard antidepressants. They target the brain chemical (neurotransmitter) serotonin. They are effective and have very moderate side effects. Some may be beneficial in treating anxiety and certain subtypes of depressive disorders unresponsive to previous drugs, including premenstrual dysphoric disorder and seasonal affective disorder, atypical depression, and recurrent brief depression.
Other neurotransmitter inhibitors. These drugs target neurotransmitters other than or in addition to serotonin, such as norepinephrine. Many are proving to be effective in patients who do not respond to standard antidepressants or in specific patients, such as smokers who want to quit or patients with chronic pain.
Tricyclic antidepressants (TCAs). These drugs are effective but can have severe adverse effects, particularly in older people.
Monoamine oxidase inhibitors (MAOIs). These drugs include newer selective MAOIs. MAOIs are the most effective antidepressants for atypical depression, but have some severe side effects and require restrictive dietary rules.
St. John's wort and other herbal remedies are included in the Lifestyle section of this report.

Approach and Duration of Initial Treatment. The guidelines for the duration of an initial antidepressant regimen is as follows:

Patients should start at a low dose, which is increased over a period of 5 - 10 days.
Patients should see their doctor every 1- 2 weeks until substantial improvement occurs. It may take 4 - 8 weeks before a patient experiences the effects of any antidepressant.
Side effects usually diminish within 1 - 4 weeks. (Exceptions may be weight gain and sexual dysfunction.)
If no improvement occurs, an alternative drug may be tried. More than 80% of patients respond to some antidepressant, although specific drugs are helpful for only about half of patients. This suggests that if one medication fails, another has a good chance of being helpful. In general, the fewer drug treatment strategies required, the better a patient’s chances of recovering completely from depression. Patients who become symptom-free have the best chance for complete recovery compared to patients whose symptoms merely improve.
In general, patients should continue taking antidepressants for at least 6 months after symptom relief to help prevent relapse. (Patients who improve within 2 weeks of taking medications may not require lengthy treatment.)

Treating Recurrence. Recurrence of depression is very common. About a third of patients will relapse after a first episode within a year of ending treatment, and more than half will experience a recurring bout of depression at some point during their lives. Among those at highest risk for early relapse and who may require ongoing antidepressants are:

Patients with at least two episodes of major depression or major depression that lasts for 2 years or longer before initial treatment.
Patients who continue to have low-level depression for 7 months after starting antidepressant treatments.

Patients may need maintenance therapy. Experts disagree, however, on the optimal length or the appropriate dosage of maintenance therapy. Some patients may need to stay on antidepressants for 1 - 2 years -- or even indefinitely. Some experts recommend withdrawing from medication after a year. (This should be done gradually, over 2 - 3 months.) If depression recurs, the patient should go back on the antidepressants.

There is no risk for addiction with current antidepressants, and many of the common antidepressants, including most standard SSRIs, have been proven safe when taken for a number of years.

Common Side Effects of Most Antidepressants. No matter how well a drug treats depression, the ability of the patient to tolerate its side effects strongly influences their compliance with therapy. Lack of compliance is probably the major barrier to success. Side effects can be avoided or moderated if any regimen is started at low doses and built up over time. Although specific side effects are discussed under individual drugs, there are a few that are common to many of them:

Sexual dysfunction is a common side effect of many of the standard antidepressants and some of the newer drugs. These side effects can be particularly distressing for patients on maintenance treatment who otherwise feel well. Some of the newer antidepressants, such as bupropion, may be effective alternatives without as high a risk for this problem. Sildenafil (Viagra), used for erectile dysfunction in men, may help reverse sexual dysfunction from antidepressants. It does not heighten sexual interest, however.
An increased risk of oral health problems caused by dry mouth is associated with long-term use of most antidepressants. Patients can increase salivation by chewing gum, taking vitamin C tablets, using saliva substitutes, and rinsing the mouth frequently.
Virtually all antidepressants have complicated interactions with other drugs; some are very important. Patients should inform the doctor of any drugs they are taking, including over-the-counter medications and herbal remedies.
Nearly all antidepressants are metabolized in the liver, so anyone with liver abnormalities should use them with caution.
Abrupt withdrawal from many antidepressants can produce severe side effects; no antidepressant should be stopped abruptly without consultation with a doctor.

In recent years, there has been concern that SSRI antidepressants may increase the risk for suicidal behavior. Of particular concern is a greater risk for suicide in young people taking these medications. While depression is itself the major risk factor for suicide, and antidepressant medication may revitalize suicidal attempts in patients who were too despondent before treatment to make the effort, evidence suggests that in some cases the medication itself can cause suicidal behavior. One specific SSRI, paroxetine (Paxil), has been definitely linked with suicidal behavioral risk in adults ages 18 - 30. In May 2006, the drug’s manufacturer warned doctors that all patients, and particularly young adults, should be carefully monitored during paroxetine therapy.

The U.S. Food and Drug Administration (FDA) has been conducting in-depth research on suicide risk and antidepressant medications. In October 2004, after careful review of scientific evidence, the FDA issued a public health advisory instructing drug manufacturers to include a "black box" warning explaining the association between antidepressant use and increased risk for suicidality (suicidal thoughts and behavior) in children and adolescents. In May 2007, the FDA proposed that the labels of antidepressant medications should include additional warnings about the risk of suicidal thoughts and behavior in young adults (ages 18 - 24) during the first 1 - 2 months of treatment. The FDA also notes there is a decreased risk of suicidality for adults age 65 years and older taking antidepressants.

The FDA based its recommendations for children and adolescents on a review of 24 clinical trials of nine antidepressant drugs. These trials enrolled over 4,400 pediatric patients and tested the safety and efficacy of SSRIs as well as other classes of antidepressants. The data suggested a greater risk for suicidality within the first few months of treatment. The average risk was minimal. Children and adolescents treated with these drugs had a 4% risk for suicidality compared with 2% for patients who received placebo. No patients in these studies actually committed suicide.

Based on these findings, the FDA recommends that caregivers monitor children being treated with antidepressants for sudden behavioral changes, and immediately notify their doctor if such changes occur. These behavioral signs include:

Agitation
Irritability
Anxiety
Panic attacks
Insomnia
Aggressiveness
Impulsivity
Hyperactivity in actions and speech
Worsening of depression
Increased thoughts of suicide

The FDA’s guidelines for medication usage recommend that patients see their doctor regularly after initiating drug treatment. The recommended schedule is:

Once per week for 4 weeks (1st month)
Every 2 weeks for the next month (2nd month)
At the end of week 12 following the start of drug treatment (3rd month)
More frequently if changes in mood or behavior occur
Patients should also be closely monitored if their drug dosage is changed.

Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.

Selective serotonin-reuptake inhibitors (SSRIs) are now the first-line treatment of major depression. They work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). There are no significant differences among SSRI brands in effectiveness for treating major depressive disorder, although individual drugs may have different side effects or benefits for specific patients. At this time, fluoxetine is the only one of these drugs to be approved for children over age 7 and adolescents.

Because they act specifically on serotonin, SSRIs have fewer side effects than older antidepressants, which have more widespread effects in the body.

Candidates for SSRIs. SSRIs appear to help people with the following conditions:

Mild to moderately severe major depression
Seasonal affective disorder
Dysthymia
Severe premenstrual syndrome and premenstrual dysphoric disorder (PMDD) -- a repackaged form of fluoxetine (Sarafem) is the first SSRI specifically FDA-approved for PMDD. Other SSRIs and newer antidepressants are also proving to be effective
Anxiety disorders
Bulimia
Impulsive and aggressive behaviors in psychiatric patients and in people with no mental health problems

Duration of Effectiveness and Use. SSRIs take, on average, 2 - 4 weeks to be effective in most adults. They may take even longer, up to 12 weeks, in the elderly and in those with dysthymia. By 14 weeks, depression should be in remission in everyone who responds to the drugs. Unfortunately, recurrence is common once the drugs are stopped. Studies indicate that the standard SSRIs are generally safe, although it is still unclear which patients would most benefit from on-going medication. Some doctors recommend withdrawing from medication after a year. If depression recurs, then the patient should go back on the antidepressant.

Side Effects of SSRIs. Side effects may include:

Nausea and gastrointestinal (GI) symptoms usually wear off over time.
Agitation, insomnia, mild tremor, and impulsivity occur in 10 - 20% of people who take SSRIs. These symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both.
Drowsiness affects about 20% of SSRI-treated patients. Newer SSRIs, such as escitalopram (Lexapro), may have fewer of these adverse effects.
Dry mouth is a common side effect.
Patients may lack motivation, feel tired, be confused, and experience mental dullness, but this side effect is fairly rare.
Headache and flu-like symptoms may occur.
Heart palpitations and chest pain may occur.
Weight gain varies depending on the SSRI. For example, in one study patients who took paroxetine (Paxil) experienced five times the weight gain as those who took citalopram (Celexa). Patients should be encouraged to maintain a low-calorie diet and to exercise. They should be aware that some of the weight-loss medications, notably sibutramine (Meridia), can have serious interactions with SSRIs.
Sexual side effects include delayed or loss of orgasm and low sexual drive. They are a well-known side effect of SSRIs. Taking a supervised drug "holiday" on the weekend may improve sexual function during that time. Some of the newer SSRIs or other antidepressants may cause less severe impairment of sexual function.
Paroxetine (Paxil) may cause birth defects if taken during the first 3 months of pregnancy. Most reported defects have been heart-related. The most common heart abnormalities are ventricular septal defects, which are holes in the muscular wall that separate the main pumping chambers of the heart. Venlafaxine (Effexor) has also been associated with birth defects. Still, recent research suggests that most types of SSRI-associated birth defects are rare and the overall risks are low. Pregnant women who are being treated for major depression should not stop taking antidepressants without first talking to their doctors. [For more information on antidepressant treatment guidelines during pregnancy, see Treating Depression During and After Pregnancy in Treatment section.]

Drug Interactions. SSRIs can interact with other antidepressants such as tricyclics and, in particular, monoamine oxidase inhibitors (MAOIs). SSRIs should never be taken in combination with an MAOI or within 2 weeks after discontinuing MAOI treatment. Other serious interactions have occurred with meperidine (Demerol) and illegal substances (such as LSD, cocaine, or ecstasy). People who take SSRIs may drink alcohol in moderation, although the combination may compound any drowsiness experienced with SSRIs, and some SSRIs increase the effects of alcohol.

Withdrawal Symptoms. Cognitive problems, sleep disturbances, increase in depressive symptoms, and electric shock-like symptoms have been known to occur with sudden discontinuation of SSRIs. The symptoms are more likely to occur with antidepressants with shorter half-lives as compared with fluoxetine, which has a long half-life. The dose of the antidepressant should be slowly reduced before stopping.

These newer antidepressants target other neurotransmitters, such as norepinephrine or dopamine, alone or in addition to serotonin. In general, the advantages of the new designer antidepressants are:

They may be better tolerated than the older tricyclic compounds and even some SSRIs, although long-term side effects are not fully known in this group.
Most of these drugs have fewer adverse effects than SSRIs on sexual function.
They may be more effective than SSRIs for severely depressed patients.
Some of these drugs are helpful for additional problems -- such as insomnia, fibromyalgia and similar chronic pain syndromes, or smoking -- that may affect people with depression.

They do share some side effects with other antidepressants, including dizziness and dry mouth.

Dual Inhibitors. Dual inhibitors act directly on two neurotransmitters -- norepinephrine and serotonin. These drugs are also known as serotonin norepinephrine reuptake inhibitors (SNRIs). The following SNRIs are approved for treatment of major depression in adults:

Venlafaxine (Effexor) is similar to Prozac in effectiveness and tolerability for most patients. As with SSRIs, venlafaxine may impair sexual function. The drug can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. It can also cause uterine and vaginal bleeding unrelated to menstruation. Venlafaxine should not be taken during the last trimester of pregnancy as it can cause complications in newborn infants. Some patients report severe withdrawal symptoms, including dizziness and nausea. In 2006, the drug’s manufacturer warned of an increased overdose risk and advised doctors to prescribe their patients only small amounts of venlafaxine pills.
Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. Side effects are generally mild and include dry mouth, nausea, and sleepiness. Patients with narrow-angle glaucoma or patients with liver or kidney diseases should not take duloxetine. Because duloxetine can cause liver damage, patients who drink large quantities of alcoholic beverages should not take it. Signs of liver damage include itching, dark urine, yellowing of skin and eyes (jaundice), and fatigue. Patients should immediately contact their doctor if they experience these symptoms.
Mirtazapine (Remeron) can cause sleepiness, increased appetite, weight gain, and dizziness.

Other Antidepressants with Effects on Multiple Neurotransmitters. Bupropion (Wellbutrin, Zyban) affects the reuptake of serotonin, norepinephrine, and dopamine -- a third important neurotransmitter. In addition to depression, bupropion is also approved for smoking cessation and for treating seasonal affective disorder (SAD). Bupropion causes less sexual dysfunction than SSRIs. About 25% of patients experience initial weight loss. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion has a risk for seizures, which increases with higher doses. High doses may also cause dangerous heart arrhythmias.

Before the introduction of SSRIs, tricyclics were the standard treatment for depression.

Tricyclics are sometimes grouped into two categories:

Tertiary amines include amitriptyline (Elavil, Endep) and imipramine (Tofranil).
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects, including drowsiness, than tertiary amines, but they are as toxic in high amounts.

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).

Tricyclics are as effective for treating depression but they have many side effects. They may offer benefits for many people with dysthymia, who generally do not respond to SSRIs. They may also be prescribed in lower dosages to be taken at night to help with insomnia.

Side Effects of Tricyclics. Side effects are common with these medications. In fact, in an analysis of studies, more tricyclic users discontinued their drugs due to side effects than did SSRI or MAOI users. Those most often reported include:

Dry mouth
Constipation
Blurred vision
Sexual dysfunction
Weight gain
Difficulty urinating
Drowsiness
Dizziness -- blood pressure may drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects:

They tend to cause disturbances in heart rhythm, which can pose a danger for some patients with certain heart diseases. Care should be taken when these medications are prescribed to the elderly and to those at risk of overdose.
Also of concern are reports that tricyclics, particularly imipramine as well as mianserin and dothiepin, may increase the risk for a lung disease called idiopathic pulmonary fibrosis (IPF), which can cause lung inflammation and scarring. Initial symptoms are breathlessness and dry cough.
Tricyclics can be fatal with an overdose.
Protriptyline can cause sun sensitivity. People who take this drug should take precautions against sunlight when they go outdoors.

Monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, an enzyme which has negative effects on many of the neurotransmitters that are important for well-being. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate). Because these drugs can have very severe side effects, they are usually prescribed only when other types of antidepressants do not help. Research indicates that MAOIs are an effective option for atypical and treatment-resistant depression.

Newer MAOIs, such as selegiline (Eldepryl, Movergan), target only one form of the MAOI enzyme. They may cause fewer side effects than older MAOIs. In 2006, a skin patch form of selegiline (Emsam) was approved for treatment of major depressive disorder in adults.

Candidates for MAOIs. MAOIs may be effective for the following conditions:

Atypical depression
Eating disorders
Post-traumatic stress disorder
Borderline personality

Side Effects. MAOIs commonly cause the following side effects:

Orthostatic hypotension (a sudden drop in blood pressure upon standing)
Drowsiness or insomnia
Dizziness
Sexual dysfunction
The most serious side effect is severe hypertension (high blood pressure), which can be brought on by eating certain foods having high tyramine content. Such foods include aged cheeses, most red wines, sauerkraut, vermouth, chicken livers, dried meats and fish, canned figs, fava beans, and concentrated yeast products.
MAOIs can cause birth defects and should not be taken by pregnant women.

Very dangerous side effects, such as serotonin syndrome, can occur from interactions with other antidepressants, including SSRIs. Serotonin syndrome is a potentially fatal condition that is caused by the interaction of serotonergic drugs. Symptoms include confusion, agitation, sweating and shivering, and muscle spasms. There should be at least a 2-week break between taking MAOIs and other antidepressants. MAOIs can have serious interactions with other drugs as well, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctors any other medications they are taking.

If patients fail to respond to antidepressants, doctors may try adding on a different type of drug. (This combination strategy is called “augmentation” or “adjunctive treatment”.) Atypical antipsychotics are drugs that are usually prescribed for schizophrenia or bipolar disorder, but they can also play a role in the treatment of severe depression. In 2007, aripiprazole (Abilify) was approved in combination with antidepressant therapy for treatment of adults with major depressive disorder. Investigators are also studying whether combination treatment with the atypical antipsychotic risperidone (Risperdal) can help patients with major depression achieve remission.

Ketamine. Ketamine, an anesthetic drug, may be helpful for patients with severe treatment-resistant depression. In a small preliminary study, a single intravenous dose of ketamine helped patients quickly recover from depression within 2 hours, and some patients sustained benefits for up to a week. (Standard antidepressant drugs usually take about 8 weeks to have an effect.) Ketamine blocks the NMDA brain protein receptor, which is involved in glutamate regulation. Glutamate is a brain chemical that is thought to be involved in depression.

Psychotherapy

Among the various psychotherapies, cognitive-behavioral therapy appears to be the most effective approach. If psychotherapy is used alone without medications, benefits should be evident within 8 weeks and symptoms should be fully resolved by 12 weeks. If these conditions are not met, then the patient should strongly consider antidepressant drugs.

In a major analysis of four randomized comparative studies, cognitive behavior therapy worked as well as antidepressants in treating severe depression for many patients. Much of the success of psychologic therapy depends on the skill of the therapist. Many studies suggest that combining cognitive therapy with antidepressants offer the greatest benefits for many patients, particularly for dysthymia (chronic depression).

Medical evidence also has found that the benefits of cognitive therapy persist after treatment has ended. Cognitive behavioral therapy has been shown to help prevent future suicide attempts in patients with a history of suicidal behavior.

Best Candidates. Cognitive therapy may be particularly helpful for the following patients:

Patients with atypical depression
Adolescents with mild symptoms of major depression
Women with non-psychotic postpartum depression
Children of parents with the disorder -- in this case, therapy should involve the whole family.
Cognitive therapy does not appear to be as beneficial as antidepressants for most patients with dysthymia.

Approach. This approach focuses on identification of distorted perceptions that patients may have of the world and themselves, on changing these perceptions, and on discovering new patterns of actions and behavior. These perceptions, known as schemas, are negative assumptions developed in childhood that can precipitate and prolong depression. Cognitive therapy works on the principle that these schemas can be recognized and altered, thereby changing the response and eliminating the depression.

First, the patient must learn to recognize depressive reactions and thoughts as they occur, usually by keeping a journal of feelings about, and reactions to, daily events.
The patient is often given "homework" that tests old negative assumptions against reality and demands different responses.
Then, the patient and therapist examine and challenge these entrenched and automatic reactions and thoughts.
As the patient begins to understand the underlying falseness of the assumptions that cause depression, they can begin substituting new ways of coping.

Over time, such exercises help build confidence and eventually alter behavior. Patients may take group or individual cognitive therapy. Cognitive therapy is a time-limited treatment, typically lasting 12 - 14 weeks. Extending this period, however, may help prevent relapse. In one study, therapy was continued for 10 sessions over an additional 8 months. This extended treatment significantly reduced the risk of recurrence. In fact, some experts believe that short-term therapy is not effective for patients with chronic or relapsing psychiatric disorders.

Based in part on psychodynamic theory, interpersonal therapy acknowledges the childhood roots of depression, but focuses on symptoms and current issues that may be causing problems. IPT is not as specific as cognitive or behavioral therapy, and all work is done during the sessions. The therapist seeks to redirect the patient's attention, which has been distorted by depression, toward the daily details of social and family interaction. The goals of this treatment method are improved communication skills and increased self-esteem within a short period (3 - 4 months of weekly appointments) of time. Among the forms of depression best served by IPT are those caused by distorted or delayed mourning, unexpressed conflicts with people in close relationships, major life changes, and isolation.

The intent of supportive psychotherapy or attention intervention is to provide the patient with a nonjudgmental environment by offering advice, attention, and sympathy. Supportive therapy appears to be particularly helpful for improving compliance with medications by giving reassurance, especially when setbacks and frustration occur.

Other Treatments

Electroconvulsive therapy (ECT) is commonly called shock treatment. It has received bad press, in part for its potential memory-depleting effect. Since its introduction in the 1930s, ECT has been significantly refined, and is now considered an effective and safe treatment for severe depression in the appropriate situation. It is especially effective for patients with severe depression who experience delusions and hallucinations. Maintenance ECT may also help prevent relapse.

Candidates for ECT. ECT may be helpful for the following patients with severe depression:

Patients who cannot, for any reason, take antidepressant drugs
Suicidal patients
Elderly patients who are psychotic and depressed
Pregnant women with severe depression
Patients with certain heart problems
Young patients who fit the adult criteria for ECT

The Procedure. In general, hospitalization is not necessary. ECT involves the following steps:

The patient receives a muscle relaxant and short-acting anesthetic.
A small amount of electric current is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
Most patients receive 6 treatments, spaced every 2 - 5 days. Others receive up to 15 treatments, followed by 6 - 12 additional treatments spaced every other week or longer for another 2 - 4 months.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Concerns about permanent memory loss appear to be unfounded.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses that target affected areas of the brain. This investigational treatment is similar to electroconvulsive therapy (ECT) but, unlike ECT, it is more precise. However, it is not yet clear whether it as effective as ECT. Researchers are continuing to refine rTMS techniques to improve treatment outcomes.

Vagus nerve stimulation (VNS) is a procedure that is effective for certain patients with epilepsy, and is now showing some success in patients with treatment-resistant depression

VNS involves implanting a battery-powered device under the skin in the upper left of the chest. The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. The vagus nerve travels to areas of the brain that control functions such as sleep and mood.

Studies report response rates of 35 - 46% in appropriate candidates with treatment-resistant depression. VNS is approved by the FDA for long-term treatment of chronic depression in adults who have not responded to typical treatments for their major depressive episode. Patients who use VNS may continue to show improvement in both their depression symptoms and quality of life.

Vagal stimulation can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Long-term studies on patients with epilepsy have reported no serious adverse side effects, although the treatment may cause lung function deterioration in some people with existing lung disease.

The vagus nerves branch off the brain on either side of the head and travel down the neck, along the esophagus to the intestinal tract. They are the longest nerves in the body, and affect swallowing and speech. The vagus nerves also connect to parts of the brain involved in seizures. In many seizures disorders, electrical stimulation of the vagus nerves may help relieve symptoms.

Phototherapy is recommended as treatment for seasonal affective disorder (SAD), particularly for patients who do not wish to try antidepressants.

The Procedure. The procedure is noninvasive and simple. It is best performed immediately after waking in the morning. The patient sits a few feet away from a box-like device that emits very bright fluorescent light (10,000 lux) for about 30 minutes every day.

Some people report mood improvement as early as 2 days after treatment. In others, depression may not lift for 3 - 4 weeks. If no improvement is experienced after that, depressive symptoms will be unlikely to respond to phototherapy. Phototherapy may work best when combined with cognitive behavioral therapy.

Side Effects. Side effects include headache, eye strain, and irritability, although these symptoms tend to disappear within a week. Patients taking light-sensitive drugs (such as those used for psoriasis), certain antibiotics, or antipsychotic drugs should not use light therapy. Patients should be examined by an ophthalmologist before undergoing this treatment.

A surgical technique called cingulotomy interrupts the cingulate gyrus, a bundle of nerve fibers in the front of the brain, by applying heat or cold. A variation of this procedure using MRI scans to guide the surgeon produced long-term improvement in 53 - 78% of patients with severe intractable depression. The procedure is generally safe with few serious complications. It does not affect intellect or memory.

Some small studies have suggested that acupuncture may help in relieving depression. Larger studies are required to confirm its benefits.

Lifestyle Changes

St. John's wort (Hypericum perforatum) is an herbal remedy that may help some patients with mild-to-moderate depression. It does not appear to help patients with moderate or severe depression.

The herb St. John's wort is believed to be helpful in relieving mild-to-moderate depression, but should only be taken under a doctor's supervision. Manufacturers of herbal supplements do not need FDA approval to sell the products.

This herbal substance is not regulated, and there is no guarantee of quality in any brands currently available. In fact, in a 2003 study, only 2 of 54 St. John's products bought in Canada and the U.S. contained concentrations of the active ingredients that fell within 10% of the claims on the labels.

The following guidelines are recommended:

People with depression should not use St. John's wort without consulting a doctor. Children and pregnant or nursing women should not take this substance.
People should purchase brands only from well-established manufacturers.
Although no specific dose levels have been established, evidence suggests taking 900 mg daily (300 mg taken 3 times a day or 450 mg taken twice a day).
It takes between 2 - 3 weeks for the herb to have an effect.
St. John's wort should not be combined with other antidepressants. This herb may also interact with other types of medications and increase or decrease their potency. St. John's wort can increase the risk for bleeding when used with blood-thinning drugs. It can also reduce the strength of certain drugs including cancer and HIV treatments.

Side Effects. Side effects are uncommon but may include nausea, dry mouth, allergic reactions, and fatigue. This herb may increase sensitivity to light (photosensitivity). Some people have reported temporary nerve damage after sun exposure, specifically pain and tingling on sun-exposed areas.

Carbohydrates and Tryptophan. Some people report relief from depression by eating foods or diet supplements that boost levels of tryptophan, an amino acid involved in the production of serotonin. There are high-carbohydrate drinks available over the counter that increase tryptophan levels and may alleviate depression associated with premenstrual syndrome for about 3 hours. Simply eating a high amount of carbohydrates, however, is not a solution for depression.

Impurities found in diet supplements containing L-tryptophan itself have caused cases of eosinophilia-myalgia syndrome, a condition that elevates certain white blood cells and can be fatal. Supplements containing L-tryptophan are currently banned in the U.S. by the FDA.

Fish Oil. Some evidence suggests that an imbalance in the ratio of specific fatty acids (omega-6 to omega-3) may increase the risk for depression. Both are polyunsaturated fats, but omega-6 fatty acids are mostly found in corn, safflower, soybean, and sunflower oil whereas omega-3 fatty acids are found in fish oil, canola oil, soybeans, flaxseed, and certain nuts and seeds.

The bottom line may be to increase intake of omega-3 rich foods, such as fish, nuts, and canola oil, and reduce consumption of foods containing omega-6 fatty acids, such as corn and sunflower oils. Such a dietary approach is healthy in any case. Researchers are studying whether eating fish or taking fish oil supplements can reduce depression. Small preliminary studies suggest that these dietary approaches may be helpful for some patients. Scientists are also investigating which type of fish oil compound -- eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) -- provides the greatest benefit.

Omega-3 fatty acids, found in oily fish and flaxseed and canola oils, may be beneficial to people with depression.

Vitamins and Other Supplements. Certain B vitamins have been associated with some protection against depression.

Vitamin B-3 (niacin) is important in the production of tryptophan and is produced from processing vitamin B3 (niacin). Dietary sources of niacin include oily fish (such as salmon or mackerel), pork, chicken, dried peas and beans, whole grains, seeds, and dried fortified cereals.
Vitamin B-12 and calcium supplements may help reduce depression that occurs before menstruation. One study also suggested that calcium might help prevent postpartum depression.
Low levels of folate, a B vitamin, may be associated with depression. Researchers are studying whether folate supplements may help enhance the effectiveness of SSRIs and other antidepressants.

Increasingly studies are reporting major benefits from exercise for people with depression.

Aerobics. Either brief periods of intense training or prolonged aerobic workouts can raise chemicals in the brain, such as endorphins, adrenaline, serotonin, and dopamine that produce the so-called runner's high. And, of course, weight loss and increased muscle tone can boost self-esteem.

Yoga. Yoga practice, which involves rhythmic stretching movements and breathing, may help improve and stabilize mood.

Click the icon to see an image depicting the practice of yoga.

A strong network of social support is important for both prevention and recovery from depression. Support from family and friends must be healthy and positive. One study of depressed women showed, however, that overprotective as well as very distant parenting was associated with a slow recovery from depression. Studies indicate that people with strong spiritual faiths have a lower risk for depression. Such faith does not require an organized religion. People with depression might find solace from less structured sources, such as those that teach meditation or other methods for obtaining spiritual self-fulfillment.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.dbsalliance.org -- Depression and Bipolar Support Association
www.fda.gov/cder/drug/antidepressants -- FDA Antidepressant Use in Children, Adolescents, and Adults
www.parentsmedguide.org -- American Psychiatric Association-sponsored information on pediatric antidepressants
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- American Psychiatric Association
www.apa.org -- American Psychological Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.postpartum.net -- Postpartum Support International
www.mentalhealth.samhsa.gov -- National Mental Health Information Center
www.mentalhealth.samhsa.gov/suicideprevention/concerned.asp -- National Strategy for Suicide Prevention (if contemplating suicide, call 1-800-273-TALK)
www.suicidology.org -- American Association of Suicidology

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Review Date:
12/25/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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Schizophrenia

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Medications
Therapy
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the Food and Drug Administration approved risperidone (Risperdal) and aripiprazole (Abilify) for treatment schizophrenia in teenagers. These drugs are the first atypical antipsychotics approved specifically for children.
Paliperidone (Invega) is the newest atypical antipsychotic drug approved for treatment of schizophrenia in adults. Paliperidone is chemically related to risperidone.

Diabetes Risk and Atypical Antipsychotics

In 2007, the manufacturer of olanzapine (Zyprexa, Symbex) added new warnings to the drug’s prescribing label. The new label reflects that olanzapine appears to cause high blood sugar, a risk factor for diabetes, more than other atypical antipsychotics. Olanzapine can also cause weight gain and increased levels of triglycerides and total cholesterol.
Aripiprazole and ziprasidone (Geodon) cause less weight gain and fewer risks for metabolic problems than other atypical antipsychotics, indicates a 2007 study in the Journal of Clinical Psychiatry.
All patients who are treated with atypical antipsychotic drugs should be monitored regularly for changes in blood sugar and cholesterol levels.

Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) is an investigational technique that is showing promise in helping quiet the voices associated with auditory hallucinations, according to a 2007 review of clinical trials. About 50 - 80% of people with schizophrenia experience auditory hallucinations. With rTMS, an electromagnet is placed on the scalp, which generates magnetic pulses that stimulate the brain’s cerebral cortex. Further clinical studies are currently being conducted at various research centers.

Introduction

Schizophrenia is a group of psychotic disorders that interfere with thinking and responsiveness. It is a disease of the brain, just like Alzheimer's and Parkinson's diseases. The term schizophrenia, which means "split mind," was first used in 1911 by Swiss psychiatrist Eugen Bleuler to categorize patients whose thought processes and emotional responses seemed disconnected. Despite its name, the condition does not cause a split personality.

Schizophrenia is a group of psychotic disorders characterized by disturbances in perception, behavior, and communication that last longer than 6 months. (This includes psychotic behavior.) A person with schizophrenia has deteriorated occupational, interpersonal, and self-supportive abilities.

Schizophrenia is characterized by the following symptoms:

Delusions
Hallucinations
Disordered thinking
Emotional unresponsiveness

Because symptoms of schizophrenia arise from various physical processes and respond differently to treatments, some experts recommend classifying the disease based on the presence of the following symptom groups:

Negative symptoms (including apathy and social withdrawal)
Psychotic symptoms
Disordered thinking

Some experts group psychotic and disordered thinking into a single category called positive symptoms.

The disease is complicated by the fact that although a schizophrenic patient may have more than one symptom, the patient rarely has all of them. Symptoms also often go into remission.

Causes

No single cause can account for schizophrenia. Rather, it appears to be the result of multiple causes such as genetic factors, environmental and psychological assaults, and possible hormonal changes that alter the brain's chemistry.

Brain scans using magnetic resonance imaging (MRI) have shown a number of abnormalities in the brain's structure associated with schizophrenia. Such problems can cause nerve damage and disconnections in the pathways that carry brain chemicals.

Because these problems tend to show up on brain scans of people with chronic schizophrenia rather than newly diagnosed patients, some experts believe they may be a result of the disease and its treatments rather than a cause. (Medications used for schizophrenia can also cause brain shrinkage over time.)

Abnormal Brain Activity and Volume. Imaging techniques have revealed abnormal brain activity and shrinkage (reduced volume) in the brains of people with schizophrenia. Of particular importance are those in the prefrontal cortex, which contains the white matter of the brain, and the temporal lobes, which contain the limbic system.

The limbic system of the brain is a group of structures that control emotions and behavior. This system (in particular, the hippocampus and amygdala) is involved in the formation of long-term memory, and is closely associated with the olfactory structures, which play a role in the sense of smell.

Click the icon to see an image of gray and white matter of the brain.

Shrinkage of the prefrontal cortex has been seen in many patients with schizophrenia. This can damage nerve cells and impair the connections that are required for verbal memory, attention, decision-making, reasoning, aggression, and meaningful speech. Impairment in the left side of the cortex is also associated with auditory hallucinations (hearing voices). Not all patients have this deficit.
Shrinkage in the limbic areas of the brain is associated with problems finding words. The limbic areas of the brain contain the hypothalamus (controls physiological functions), amygdala (responsible for arousal and emotional states), and hippocampus (the part of the brain that makes memories). A number of studies have specifically noted smaller left hippocampi in people with schizophrenia. Activity in the limbic area in general is related to emotions and memory, and abnormalities there are also associated with positive symptoms, including delusions, hallucinations, and disordered thinking.

Abnormal Brain Chemicals. Schizophrenia is associated with an unusual imbalance of neurotransmitters (chemical messengers between nerve cells) and other brain chemicals, such as dopamine overactivity, glutamate, reelin, and others. Whether any changes in these chemicals in the brain is a cause or a consequence of schizophrenia remains unclear.

Abnormal Circuitry. Abnormalities in brain structure are also reflected in the disrupted connections between nerve cells that are observed in schizophrenia. Such miswiring could impair information processing and coordination of mental functions. For example, auditory hallucinations may be due to miswiring in the circuits that govern speech processing. Strong evidence suggests that schizophrenia involves decreased communication between the left and right sides of the brain.

Schizophrenia undoubtedly has a genetic component. The risk for inheriting schizophrenia is 10% in those who have one immediate family member with the disease and about 40% if the disease affects both parents or an identical twin. Family members of patients also appear to have higher risks for the specific symptoms (negative or positive) of the relative with schizophrenia.

Researchers are seeking the specific genetic factors that may be responsible for schizophrenia in such cases. Current evidence suggests that there are a multitude of genetic abnormalities involved in schizophrenia, possibly originating from one or two changes in genetic expression. Scientists are beginning to discover the ways in which specific genes affect particular brain functions and cause specific symptoms. Genes that have been studied include the neuregulin-1 gene, the OLIG2 gene, and the COMT gene.

Heredity does not explain all cases of the disease. About 60% of people with schizophrenia have no close relatives with the illness.

The case for viruses as a cause of schizophrenia rests mainly on circumstantial evidence, such as living in crowded conditions. The risk is higher for people who are born in cities than in the country. The longer one lives in the city, the higher the risk. The following are some studies suggesting an association:

Winter and Spring Births. The risk for schizophrenia worldwide is 5 - 8% higher for those born during winter and spring, when colds and viruses are more prevalent.
Large Families. The risk for schizophrenia is also greater in large families in which there are short intervals between siblings (2 or fewer years). Such observations suggest that exposure to infection early in infancy may help set the stage for later development of the disease.
Pregnant Mother's Exposure to Viruses. The mother's exposure to viral infections such as rubella, measles, chicken pox, or others while the infant is in the womb has also been associated with a higher risk for schizophrenia in her child.
Researchers are trying to identify specific viruses that may be responsible for some cases. Of particular interest is research finding evidence of a virus that belongs to the HERV-W retrovirus family in 30% of people with acute schizophrenia.

Some researchers have found an association between some cases of schizophrenia and toxoplasmosis, a parasite carried by cats and other domestic animals. Several studies suggest that patients with schizophrenia have an increased prevalence of antibodies to toxoplasmosis. Toxoplasmosis can lie dormant in the nervous system and migrate to the brain over many years.

Although parental influence is no longer believed to play a major role in the development of schizophrenia, it would be irresponsible to ignore outside pressures and influences that may exacerbate or trigger symptoms. The prefrontal lobes of the brain, the brain areas often thought to lead to this disease, are extremely responsive to environmental stress. Given the fact that schizophrenic symptoms naturally elicit negative responses from the patient's circle of family and acquaintances, negative feedback may intensify deficits in a vulnerable brain and perhaps even trigger and exacerbate existing symptoms.

Risk Factors

Schizophrenia is the most common psychotic condition.

Schizophrenia can occur at any age, but it tends to first develop (or at least become evident) between adolescence and young adulthood. Schizophrenia in children is likely to be severe. Although the risk of schizophrenia declines with age, its incidence has been known to peak in those who are about 45 years old, and again in people who are in their mid-60s (mostly women). Late-onset schizophrenia that develops in the 40s is most likely to be the paranoid subtype with fewer negative symptoms or learning impairment. Such patients usually have functioned at a near-normal level until structural deficits in the brain break down.

Although schizophrenia affects both men and women, there are some differences:

Men tend to develop schizophrenia between the ages of 15 - 24. Paranoid schizophrenia may be more common in men, and symptoms tend to be more severe.
The onset in women is usually slightly later, between ages 25 - 34, and the symptoms tend to be less severe. The earlier a girl starts menstruation, the longer she is protected against schizophrenia. Schizophrenia is more severe during a woman's menstrual cycle when estrogen levels are low. Such findings and other evidence suggest that estrogen may have nerve-protecting properties. For example, the higher the estrogen levels in female patients with schizophrenia, the better their mental functions.

People with schizophrenia span the full range of intelligence. In fact, one study reported that a higher than expected number of people who develop schizophrenia had been intellectually gifted children. Research suggests, however, that a decline in IQ scores during childhood may be a sign of potential psychotic symptoms in adults.

No cultural or geographic group is immune from schizophrenia, although the course of the disease seems to be more severe in developed countries. However, the content of delusions may vary depending on a person's culture. According to one study, European patients were more apt to have delusions of poisoning or religious guilt while in Japan the delusions were most often related to being slandered.

Schizophrenia occurs twice as often in unmarried and divorced people as in married or widowed individuals. Furthermore, people with schizophrenia are eight times more likely to be in the lowest socioeconomic groups. However, these findings are likely to be a result of schizophrenia rather than a cause. Nevertheless, low income and poverty increases the risk for delayed diagnosis and treatment, and such delays could lead to more severe disease in patients with fewer resources.

Prenatal malnutrition may also play a role in the development of schizophrenia. A 2005 study found that people who were born during times of famine were more than twice as likely to develop schizophrenia as those born during years of adequate food. The association between famine and schizophrenia illustrates how environmental and biologic factors are connected. Scientists think that malnourished mothers may not get enough folate in their diet. Folate is a micronutrient important for genetic processes. Folate deficiencies may cause genetic mutations in the developing fetus that can lead to schizophrenia.

Being Left- or Mixed-Handed. The rate of left-handedness or mixed-handedness is significantly higher among patients with schizophrenia than the general population. This suggests that some neurologic pattern that may be responsible for each. (A large minority of the population is non-right handed, and very few of these people develop schizophrenia.)

Obsessive-Compulsive Disorder. Obsessive compulsive disorder (OCD) affects a significant number of schizophrenic patients. OCD is an anxiety disorder marked by obsessions (recurrent or persistent mental images, thoughts, or ideas) that may result in compulsive behaviors, repetitive, rigid, and self-prescribed routines that are intended to prevent the manifestation of the obsession. Some experts believe the behaviors exhibited in the disorder may actually be protective in people with schizophrenia in early stages.

Behavioral and Motor Problems in Childhood. Children who later develop schizophrenia often suffer from the following certain problems, including excessive shyness or minor early physical and motor-control problems. Such problems are so common, however, that their presence without any other risk factors is no cause for concern.

Father’s Age. According to some studies, the older a father is when a child is born, the greater the risk is for schizophrenia in his offspring, perhaps because of a greater chance of genetic mutations in the sperm that can be passed on. In one study, children of fathers who were 50 years old or more faced a three-fold risk for schizophrenia compared to children of fathers who were 25 or younger.

Epilepsy. A family history of epilepsy increases the chance for developing schizophrenia or similar psychosis. Scientists think that epilepsy and schizophrenia may share similar genetic or environmental factors.

Symptoms

Research indicates that symptoms in childhood strongly predict disease in adulthood. In one long-term study, over 40% of people with schizophrenia who developed the disease in young adulthood had reported psychotic symptoms by age 11. For children with a family history of schizophrenia, the following inherited traits may be warning signs:

Deficits in working (short-term) and verbal memory
Impairments in gross motor skills (the child's ability to control different parts of the body)
Attention deficits
A decline in verbal memory, IQ, and other mental functions

Any signs of hallucinations or delusions must be differentiated from normal childhood fantasies.

Most often, early warning signs go unnoticed, and schizophrenia usually becomes evident for the first time in late adolescence or early adulthood. Schizophrenia that starts in childhood or adolescence tends to be severe. It should be strongly noted that the traits discussed above, even combinations of them, can be present without schizophrenia.

A person with schizophrenia may have the following negative symptoms:

Lack of self confidence
Lack of emotions
Colorless speaking tones
Inappropriate reactions to events (such as laughing hysterically over a loss)
A general loss of interest in life and the ability to experience pleasure

Lack of responsiveness and poor sociability often appear in childhood as the first indications of schizophrenia. Certain imaging techniques suggest that these findings are based on biologic changes in specific parts of the brain. In many patients, however, negative symptoms do not appear until after positive symptoms develop. Negative symptoms tend to be more common than positive symptoms in older patients and typically persist after positive symptoms have been treated.

Psychotic symptoms, particularly delusions and hallucinations, are the most widely recognized manifestations of schizophrenia.

Hallucinations. A hallucination is the experience of seeing, hearing, tasting, smelling, or feeling something that doesn't really exist. Auditory hallucinations are false senses of sound such as hearing voices that go unheard by others. They are the most common psychotic symptoms, affecting about 70% of patients.
Delusions. A delusion is a fixed, false belief. It can be bizarre (such as invisible aliens have entered the room through an electric socket) or nonbizarre (such as unwarranted jealousy or the paranoid belief in being persecuted or watched).

Psychotic symptoms usually occur every now and then with periods of remission. They typically occur in men ages 17 - 30 and in women ages 20 - 40.

The symptoms of cognitive impairment and disordered thinking may occur before other symptoms of schizophrenia. They include:

A lack of attention.
Impaired information processing and an aberrant association between words and ideas. Sometimes this condition is so extreme that speech becomes incoherent and is referred to as "word salad." Patients may connect words because of similarity of sound, rather than by meaning, a condition known as "clang associations."
Memory impairment. In keeping with other aspects of disordered thinking, memory impairment in schizophrenia is likely to involve the inability to connect an event with its source into a complete and whole memory. For instance, a patient may recall and even feel a familiarity with a specific event but be unable to remember where, when, or how it took place.
Backward masking dysfunction. This is a trait in which a distraction causes a person to forget a preceding event. It might be an important symptom and a marker of schizophrenia even in people with normal working memories.

People with schizophrenia do poorly on mental tasks requiring conscious awareness, such as verbal fluency, short-term and working memory, and processing speed. However, they are no worse than the general population in underlying (implicit) learning, such as grammar skills, vocabulary, and spatial skills (such as map reading). Some experts believe that impaired verbal memory in schizophrenia is a consequence of depression and slowness, but not a result of the disease process.

People with schizophrenia may experience other symptoms, such as intolerance of heat (often associated with antipsychotic medications) and a reduced sense of smell.

The course of the disease varies from one patient to the next. Symptoms of psychosis can become gradually or suddenly evident.

In up to a third of patients, the disease is unrelenting and progresses from the first episode onward.
In others, schizophrenia follows a fluctuating course with psychotic flare-ups, followed by remissions.
In one study, 31% of patients experienced a complete remission of symptoms within 3 years after one or more episodes. Women are more likely to go into remission, possibly because of some protective effect of estrogen on the brain.

Typically, patients develop considerable cognitive dysfunction (disordered thinking) within the first 4 - 5 years of the onset of psychotic symptoms. Some evidence indicates that the physical disease process in schizophrenia is progressive, as with Alzheimer's and Parkinson's disease. However, schizophrenia does not progress in the same way as those two diseases. Unlike Parkinson's and Alzheimer's, cognitive function usually eventually stabilizes. Psychosis, disorganized thought, and negative symptoms often improve over time, although, even in such cases, deficits in verbal memory usually persist. (Thought disorder often improves along with improvements in negative symptoms.)

Complications

Schizophrenia has a devastating effect on all aspects of human thought, emotion, and expression. Only about 20% of patients reach full recovery after a first episode, but new drugs are offering significant hope for improving quality of life.

Studies have reported that people with severe mental illnesses suffer more from serious health problems than those without mental disorders, and they are less likely to receive medical help. Substance abuse is a significant factor in this higher risk.

Research has suggested an increased risk of diabetes among people with schizophrenia. In addition, many new antipsychotic medications can elevate blood sugar levels. Patients taking atypical antipsychotics drugs -- such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, and ziprasidone -- should receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels. (See “Diabetes Risk and Atypical Antipsychotics” in Medications section.)

Depression is common later in adulthood. Although this mood disorder can certainly be a result of the negative social impact of schizophrenia, some experts believe that depression is part of the disease process itself.

Studies indicate that after 20 - 30 years, half of patients are able to care for themselves, work, and participate socially. Support services and appropriate housing improve this outcome. Unsurprisingly, the decline in status, including the inability to earn a living, is less steep when there are more financial resources and fewer emotional disorders at the outset of symptoms. Also, on average, the later the onset of the disease, the milder the social impact. The long-term effects on work and relationships, however, are usually severe and difficult to repair, even if symptoms improve.

In one study, about half of patients experienced some decline in IQ (10 points or more), but intelligence scores remained the same in the other half. Experts believe that a decline in IQ reflects early nerve damage but that it is not an inevitable consequence of the disease process.

In spite of the sometimes frightening behavior, people with schizophrenia are no more likely to behave violently than are those in the general population. In fact, these patients are more apt to withdraw from others or to harm themselves.

Suicide. Between 20 - 50% of patients with schizophrenia attempt suicide, and an estimated 9 - 13% commit suicide.

The general risk for suicide is higher at certain times in the course of the disease:

Within the first 5 years of onset of the disease
During the first 6 months after hospitalization
Following an acute psychotic episode

The widespread use of antipsychotic drugs over the past decade does not appear to have had much effect on suicide rates. In fact, evidence suggests that the use of these drugs as a way of reducing hospitalization time is increasing the incidence of suicide. Depression, not delusions, appears to be the most important motive for suicide in these patients. Suicide risk is also associated with prior suicide attempts, drug abuse, agitation, poor treatment compliance, fear of mental deterioration, and personal loss.

Smoking and Other Addictions. Most people with schizophrenia abuse nicotine, alcohol, and other substances. Substance abuse, in addition to its other adverse effects, increases non-compliance with antipsychotic drugs in the schizophrenic patient and may worsen symptoms.

Smoking is of special interest. According to one study, up to 88% of schizophrenic patients are nicotine dependent. Biologic and genetic factors may be partially responsible for the addiction in this particular group. Nicotine helps reduce psychotic symptoms and impulsivity, perhaps by inhibiting the activity of a protein called monoamine oxidase B (MAO- B), which is linked to improved mood and possibly to nerve protection. Smoking for schizophrenics, then, may be a form of self-medication.

Obesity and Diabetes. Obesity is very common in patients with schizophrenia. Factors that contribute to obesity and diabetes in these patients include unstable lifestyle, low social economic status, and side effects of any antipsychotic medications. Patients should be monitored closely for onset diabetes.

Family members suffer from grief, long-term guilt, and many emotional issues when faced with a schizophrenic loved one. If these patients commit suicide, the effects can be devastating.

In the 1970s, tens of thousands of patients were put on antipsychotic drugs and released from institutions into the community, a concept called deinstitutionalization. In spite of these attempts to reduce mental hospital costs, schizophrenia still accounts for 40% of all long-term hospitalization days. More than half of patients with schizophrenia require public assistance within a year of their reentry into the community.

Diagnosis

The doctor will use one or more verbal screening tests to help determine whether a patient's symptoms meet the criteria for schizophrenia. Because no single symptom is specific to schizophrenia, a diagnosis may be made when one or more of the following conditions is present:

If a patient has at least one active flare-up lasting a month or more. The flare-up consists of at least two characteristic symptoms (such as hallucinations, delusions, evidence of disorganized thinking, and emotional unresponsiveness with a flat speaking tone).
If the patient has particularly bizarre delusions or hallucinations, even in the absence of other characteristic symptoms.
If certain symptoms are present for at least 6 months, even in the absence of active flare-ups. Such symptoms include marked social withdrawal, peculiar behavior (talking to oneself, severe superstitiousness), vague and incoherent speech, or other indications of disturbed thinking. The patient's social and personal relationships would also have deteriorated since the onset of symptoms.

Experts are investigating tests of specific phenomenon that might suggest a higher risk for the presence of schizophrenia.

Eye Tracking Dysfunction. A dysfunction in eye tracking is a genetic trait that is strongly associated with schizophrenia and may reflect abnormalities in the frontal regions of the brain. (Some experts believe that this is such a powerful marker in patients with close relatives with schizophrenia that it can be used as a predictor. This trait can be detected only by a health professional using special equipment.)
Impaired Prepulse Inhibition. Prepulse inhibition (PPI) is a phenomenon in which a low sound (weak stimulus) that occurs before a loud sound (a strong stimulus) reduces a patient's startle response to the loud sound. PPI is impaired in schizophrenia.

The common hallmarks of schizophrenia are also symptoms that can occur in dozens of other psychologic and medical conditions, as well as with certain medications. Shared symptoms include delusions, hallucinations, disorganized and incoherent speech, a flat tone of voice, and bizarrely disorganized or catatonic behavior (such as lack of speech, muscular rigidity, and unresponsiveness).

Among the conditions that may resemble schizophrenia are the following:

Depression. Delusions that focus on a physical abnormality or disease that isn't real, known as somatic delusions, sometimes occur in people with depression.
Bipolar Disorder. Paranoia and delusions of grandeur (the belief that one has a special power or mission) can occur in people with bipolar disorder during the manic phase. In fact, sometimes it is difficult even for experts to differentiate between these two disorders. Evidence suggests that they may share certain genetic factors that make some families vulnerable to either one.
Schizophrenia-Like Psychoses. Several other conditions exhibit schizophrenia-like psychoses but do not meet the diagnostic criteria for schizophrenia. Such conditions may be variations of entirely different diseases and are classified as schizoaffective disorder, schizophreniform psychosis, and atypical and brief reactive schizophrenia.
Alcohol and Drug Abuse. Either substance abuse itself or withdrawal from drugs or alcohol can trigger psychosis. Because of the high risk for substance abuse among people with schizophrenia, it is important that the health professional distinguish psychosis triggered by drugs or alcohol from a schizophrenic episode. Usually, the diagnosis is confirmed if the psychosis ends after withdrawal from drugs or alcohol, and returns if the patient returns to alcohol or substance abuse.
Medical Illnesses. Other causes of psychotic symptoms include cancer in the central nervous system, encephalitis, neurosyphilis, thyroid disorders, Alzheimer's disease, epilepsy, Huntington's disease, multiple sclerosis, stroke, Wilson's disease, some vitamin B deficiencies, and systemic lupus erythematosus.
Medication Reactions. Many medications may induce psychosis as a side effect, and some can precipitate delusions and severe confusion. Such medication-induced symptoms are most often observed in elderly patients.

Many brain imaging techniques can detect changes in the brain structure that relate to specific sets of symptoms in schizophrenia. These imaging techniques include magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). Such techniques are used as research tools. However, research continues in evaluating whether they may be useful for identifying candidates for early treatment among high-risk young people with early warnings signs of schizophrenia and brain damage.

Treatment

Schizophrenia is categorized as a brain disease, not a psychological disorder, and drug treatment is the primary therapy. Studies indicate, however, that an integrated approach better prevents relapses than routine care (medication, monitoring, and access to rehabilitation programs).

Integrated Approach. An integrated approach, which may help to ease psychotic symptoms, may include:

Motivational interviewing to encourage the patient's commitment to change
Use of antipsychotic medications (generally atypical or novel antipsychotics) with monitoring
Community-based rehabilitation and social skills training
Family psychotherapy
Cognitive-behavioral therapy to reduce delusions and hallucinations

Treatment of schizophrenia has traditionally focused on decreasing patients’ negative symptoms. Today, an important shift is now taking place. Doctors are now emphasizing patients’ ability to function -- shop, eat, cook, clean, do laundry, and in some cases, work independently.

Early Treatment. The earlier schizophrenia is detected and treated, the better the outcome. Patients who receive antipsychotic drugs and other treatments during their first episode are admitted to the hospital less often during the following 5 years and may require less time to control symptoms than those who do not seek help as quickly. In spite of strong evidence for the positive effects of early treatment, patients usually do not receive treatment until after 10 months of serious symptoms.

Most drugs that treat schizophrenia work by blocking receptors of the neurotransmitter dopamine. Dopamine is thought to play a major role in psychotic symptoms. Although the drugs used to treat schizophrenia have important benefits, they may also cause side effects. The most disturbing and common side effects are those known as extrapyramidal symptoms, which involve the nerves and muscles controlling movement and coordination.

The following drug classes are generally used for schizophrenia:

Typical antipsychotics. Until recently, these drugs were the mainstay treatments for schizophrenia. They include haloperidol (Haldol), chlorpromazine (Thorazine), perphenazine (Trilafon), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), and fluphenazine (Prolixin). Side effects involving the nerves and muscle movement and coordination occur in up to 70% of patients. Typical antipsychotics are sometimes referred to as “first-generation” to distinguish them from newer “second-generation” atypical antipsychotics.
Atypical antipsychotics. These newer drugs may be better tolerated than the older antipsychotics and have significantly fewer severe side effects. They include clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and palperidone (Invega).

Which Type of Drug to Choose. Experts have debated whether newer atypical antipsychotics carry a treatment advantage over the older typical antipsychotics, which are much less expensive.

Most practicing psychiatrists feel that atypical antipsychotics may work better than the older drugs. However, the additional benefits may be modest for most patients. Large, high-quality studies have compared newer and older drugs and found them to have a similar benefit.

Side effect profiles between typical and atypical antipsychotics are different. Both groups cause extrapyramidal side effects, (including muscle stiffness, tremors, and abnormal movements), but the newer atypical drugs do not seem to cause them as often. However, the atypical antipsychotics pose a higher risk for weight gain, which can lead to diabetes as well as heart disease.

One problem with most of the studies that evaluate these medications is that often more than half the patients discontinue the drugs either because of side effects or because they do not feel the medications are helping them.

In 2007, risperidone and aripiprazole became the first atypical antipsychotics approved for treatment of schizophrenia in adolescents (ages 13 - 17 years). Doctors caution that more research is needed to determine the long-term safety and efficacy of these drugs for pediatric patients.

For the severe, active phase of schizophrenia, injections of an antipsychotic drug are typically given every few hours until the patient is calm. Anti-anxiety drugs are also often administered at the same time. Some of the newer atypical drugs, such as olanzapine or risperidone, may prove to be as effective as the older antipsychotics with significantly fewer severe side effects. In patients who are being treated for the first time, improvement in psychotic symptoms may be evident within 1 - 2 days of treatment, although the full benefit of the drug usually manifeets over about 6 - 8 weeks. Thought disturbances tend to abate more gradually.

To reduce the risk of relapse, many doctors recommend that drugs be given daily for at least 1 year. Atypical drugs are increasingly being used as maintenance for those with new-onset psychosis, although the choice of the drug depends on many factors. Side effects and effectiveness vary from individual to individual. Some trial and error adjustments may be necessary when prescribing dosage amounts so that the benefits of treatment outweigh the side effects of the therapy. The doctor must monitor the drug effects carefully.

Keeping patients on maintenance therapy, however, is very difficult, and many patients stop their medication. Factors that may contribute to poor compliance include:

Lower occupational status
A history of alcohol or drugs abuse
Delusions of persecution
A history of stopping medications within the first 6 months after diagnosis

Nearly all patients experience some relapse or worsening of symptoms within 2 years of stopping maintenance medication. Recognizing signs of relapse and starting medications immediately can help prevent rehospitalization for these patients.

Antidepressants and anti-anxiety drugs may also play an important role in treating the patient with schizophrenia, particularly given the role of depression in the high rates of suicide among these patients.

Psychiatrists generally agree that current treatment should offer both medical and psychological treatment to the patient. Cognitive-behavioral approaches are showing promise. Support to the family or other caregiver is also important for the long-term improvement of people with schizophrenia.

Medications

Seven atypical antipsychotic drugs are currently approved in the United States:

Clozapine (Clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Aripiprazole (Abilify)
Ziprasidone (Geodon)
Paliperidone (Invega)

Clozapine was the first atypical drug approved (in 1989), and paliperodine the most recent approved (in 2007). Clozapine appears to have more side effects than the other atypical antipsychotics. Most of these drugs come in pill form, but some may come in liquid form or as an injection. In general, it may take up to 6 months before an atypical drug has an effect.

The atypical antipsychotics zotepine (Zoleptil) and amisulpride (Solian) are not approved for use in the United States.

Benefits of Atypical Antipsychotics.

Affect both dopamine receptors and other neurotransmitters responsible for psychotic symptoms.
Improve negative and positive symptoms.
May even improve working memory and mental functioning.
May reduce depression and hostility.
May reduce the risk for suicide (clozapine may be particularly helpful for suicide prevention).
These drugs, particularly the newer atypicals, have fewer extrapyramidal side effects than the typical antipsychotics.

Atypical antipsychotics have some significant limitations and complications, and their benefits compared to each other and to other antipsychotics are not always clear-cut. In-depth comparative studies are needed to determine which specific drugs are more effective and have fewer side effects than others.

Side Effects of Atypical Antipsychotics.

Nasal congestion or runny nose
Drooling
Dizziness
Headache
Drowsiness -- although, sometimes the drugs may cause restlessness and insomnia
Constipation
Rapid heart beat
Difficulty urinating
Skin rash
Increased body temperature
Confusion, short-term memory problems, disorientation, and impaired attention

The following are more severe side effects or complications that may occur with these drugs:

Diabetes ( See: Diabetes Risk and Atypical Antipsychotics).
Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest for aripiprazole and ziprasidone.
Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high levels of trigylcerides and total cholesterol.
Seizures.
Heat stroke.
Sudden drop in blood pressure (hypotension).
A significant drop in white blood cell count (neutropenia) and neutrophils (agranulocytosis) occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored if they take clozapine.
Extrapyramidal side effects ( See: Extrapyramidal symptoms).
Cataracts and worsening of any existing glaucoma.
Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.

In 2003, the Food and Drug Administation (FDA) requested that the strongest warning be added to the product labels of all atypical antipsychotics. This so-called black box warning advises that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The FDA recommends that:

Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.

There may also be an increased background risk of diabetes in patients with schizophrenia. As a precaution, many doctors advise that all patients treated with atypical antipsychotics receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment. Patients should also have their lipid and cholesterol levels monitored. [See In-Depth Report #60: Diabetes - type 2.]

The standard typical antipsychotic drug used for schizophrenia is haloperidol (Haldol). Others include:

Chlorpromazine (Thorazine)
Perphenazine (Trilafon)
Thioridazine (Mellaril)
Mesoridazine (Serentil)
Trifluoperazine (Stelazine)
Fluphenazine (Prolixin)

Studies have not shown any significant difference in benefits among these drugs.

The beneficial impact of these drugs is greatest on psychotic symptoms, particularly hallucinations and delusions in the early and midterm stages of the disorder. They are not very successful in reducing negative symptoms. Because of their significant side effects, many patient's stop taking the drug.

Depot therapy (long-lasting monthly injections, usually of haloperidol or fluphenazine) has been used with success in people who have difficulty complying with a daily regimen of these drugs. Researchers are studying low-dose regimens to discover if they can be effective and cause fewer side effects.

Side Effects of Typical Antipsychotics. These drugs can have adverse side effects related to many organs and systems in the body. These drugs are also known as neuroleptics, a name that comes from the severe neurological side effects that these medications can cause. Side effects include:

Extrapyramidal symptoms ( See: Extrapyramidal symptoms )
Sleepiness and lethargy -- common in the beginning but usually decreases over time
Insomnia and agitation -- in some cases
Dulling of the mind
Nausea, vomiting, diarrhea, constipation, and heartburn
Dry mouth and blurred vision
Allergic reactions
Sexual dysfunction -- a common reason why patients stop taking the drug; amantadine may help offset this side effect
Neuroleptic malignant syndrome -- rare, but can be fatal without prompt treatment
Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer
A sudden drop in blood pressure (hypotension)
An increased risk of sudden cardiac death

In general, higher potency drugs cause less drowsiness and drops in blood pressure but pose a higher risk for extrapyramidal side effects. Lower-potency drugs (such as chlorpromazine, thioridazine) are more sedating and have milder side effects.

Nearly every drug used to date for schizophrenia can cause extrapyramidal side effects to some degree. These side effects involve the nerves and muscles controlling movement and coordination.

Description of Extrapyramidal Side Effects. These effects resemble some of the symptoms of Parkinson's disease and include the following conditions:

Tardive dyskinesia is the most serious extrapyramidal side effect. It often manifests itself by repetitive and involuntary movements, or tics, most often of the mouth, lips, or of the legs, arms, or trunk. Symptoms range from mild to severe, and sometimes interfere with eating and walking. They may appear months or even years after taking the drugs. After the drug is stopped, symptoms can sometimes persist for weeks or months and may be permanent. Some people are more likely to develop these symptoms, including older patients, women, smokers, people with diabetes, and patients with movement disorders.
Acute dystonia typically develops shortly after taking an antipsychotic drug. This syndrome includes abnormal muscle spasms, particularly sustained contortions of the neck, jaw, trunk, and eye muscles.
Other extrapyramidal symptoms. Other effects are agitation, slow speech, tremor, and retarded movement. It should be noted that sometimes these symptoms mimic schizophrenia itself. In response, the doctor may be tempted erroneously to increase the dosage.

Treatment of Extrapyramidal Side Effects. In general, if extrapyramidal side effects occur from neuroleptic drugs, the doctor may first try to reduce the dosage or switch to an atypical drug. Other approaches to reduce these symptoms include:

Anti-parkinsonism drugs known as anticholinergics increase dopamine levels and help to restore balance. Among the anticholinergics sometimes used are trihexyphenidyl (Artane, Trihexy) and benztropine (Cogentin). They are not helpful for tardive dyskinesia, however. Some of these drugs may also help in managing negative symptoms of schizophrenia. The use of these drugs, however, adds to the cost and complicates management. These medicines also have their own, sometimes serious, side effects. Most experts recommend them only for patients who cannot be monitored regularly, need very high doses of powerful antipsychotic drugs, and are at risk for severe side effects. They should be stopped after 3 or 4 months, if possible. If symptoms recur, the drugs can be reinstituted. Withdrawal from anticholinergics can cause depression that can worsen schizophrenia.
Benzodiazepines may also alleviate these symptoms.

Antidepressants. Antidepressants are recommended along with antipsychotics to alleviate the depression that is so common in people with schizophrenia. One study indicated that taking antidepressants may even help prevent relapse. In spite of their benefits, fewer than half of all patients take these medications.

Anti-Anxiety Drugs. Benzodiazepines are drugs normally used to treat anxiety. They also have some modest effect on psychotic symptoms. They may be useful in the early stages of a psychotic relapse for preventing a full attack. They also are sometimes used to treat the restlessness and agitation that can occur with the use of neuroleptics. Severe side effects, including respiratory arrest, very low blood pressure, and loss of consciousness, have been reported in a few people taking anti-anxiety medication and clozapine. There is no evidence, however, of a clear danger associated with the use of these two drugs. In any case, prolonged use of anti-anxiety drugs is generally not recommended in schizophrenia. Withdrawal from these drugs should occur gradually.

Lithium. Lithium, ordinarily used for bipolar disorder, is useful for some schizophrenic patients. It appears to help those with fewer negative symptoms and without a family history of schizophrenia. However, there are no reliable criteria to predict who will benefit.

Anti-Epileptic Drugs. Drugs ordinarily prescribed for epilepsy -- such as carbamazepine (Tegretol), gabapentin (Neurontin), lamotrigine (Lamictal), or others -- are occasionally used in combination with antipsychotic drugs for patients who do not respond to standard drugs.

Estrogen Replacement in Women. Estrogen may be nerve-protective. Some investigators have proposed using estrogen therapy to help with cognitive impairment. However, evidence is weak, and cancer and cardiovascular risks of estrogen therapy must be considered.

The following are special concerns for people taking natural remedies for schizophrenia:

Gingko biloba can increase the risk for bleeding and interact with anti-clotting medications when used at high doses. Commercial gingko preparations have also been reported to contain colchicine, which can be harmful to pregnant women and people with kidney or liver problems.

Therapy

One-fifth to one-third of all patients with schizophrenia do not respond adequately to drug treatment. Many patients who have been successfully treated with medications experience the "awakenings" phenomena, which are painful reactions that are manifested as inner emotions and the recognition of real losses. The effects of the disease, in any case, are profoundly emotional. As a result, psychological therapies can be helpful for many patients.

The use of cognitive-behavioral therapy is showing particular promise for improvement in both positive and negative symptoms in some patients, and the benefits may persist after treatment has stopped. This approach attempts to strengthen the patient's capacity for normal thinking, using mental exercises and self-observation. More evidence is showing that improving patients' ability to learn, remember, and pay attention allows them to better cope with ongoing positive symptoms and lead independent lives. Patients with schizophrenia are taught to critically analyze hallucinations and examine underlying beliefs in them.

Positive social interaction is extremely important for people with schizophrenia and may help reduce symptoms, including the number of delusional moments.

Family Support. It is deeply painful for anyone to interact with a loved one whose behavior is determined by a mysterious internal mechanism that has gone awry. Given support and direction, however, families or other caregivers can be very helpful in a number of ways:

They can encourage patients to comply with drug treatments and to recognize early signs of serious treatment side effects.
They can be taught to recognize impending symptoms of relapse and help the patient avoid situations that might trigger them. (Symptoms for an impending relapse after remission may include feeling distant from family and friends, being increasingly bothered by persistent thoughts, and having an increased interest in religion.)

Unfortunately, the family's own mental health is often threatened. As a result, they need help almost as much as the patient. Numerous studies have shown that patients with schizophrenia do worse in families who are too emotional, hostile, critical, or even overly involved. The problem is an emotional loop:

When affection and reason have failed to bring a loved one back to reality, overly critical or emotional family members typically react with anger and frustration.
This generates anxiety and depression in patients.
The subsequent expression of these emotions by the patient triggers yet more criticism or acting out. So the cycle continues.
Eventually, out of despair and fear, the family may reject the patient completely.

Studies indicate that once the patient receives appropriate treatment and support, the family's over-emotional state also recedes. Some studies have reported that when families receive help for themselves (group support or cognitive therapy) the relapse rates for the related patients are significantly lower than for patients whose families did not seek help. Still, only a small number of families of patients with schizophrenia receive the support and education needed not only for the patient but also for themselves.

Community Treatment Programs. Community treatment programs, in which a team of professional caregivers provides treatment and support for patients in their homes, is highly beneficial and cost effective (compared to frequent hospitalization). At this time, however, only between 2 - 10% of patients now participate in such programs.

Vocational Rehabilitation. Paid work is very important in the health of the patient. One study reported that after 1 year, 40% of workers with schizophrenia who were paid for their labor reported much improvement in all symptoms, and 50% reported much improvement in positive symptoms. Those who were not paid for their work did considerably less well. (The arts and crafts activities that are often used to enhance self-esteem in rehabilitation programs offer few real benefits to the patient.)

Unfortunately, at this time, fewer than a quarter of patients with schizophrenia are in programs that help them find and keep jobs, and up to 90% of patients with severe mental problems are unemployed.

Other Treatments

Electroconvulsive therapy (ECT), often called shock treatment, has received bad press since it was introduced in the 1940s. However, refined techniques have revived its use, particularly for those with severe depression. Imaging studies have not found that current ECT techniques cause any damage to the brain's structure, and some doctors feel it is safer than drug therapy. A 2005 review of many clinical trials indicated that ECT combined with antipsychotic medication can provide rapid improvements for patients who are suicidal or severely psychotic. The review found that the combined treatment worked better than antipsychotics alone for these patients. ECT treatments are usually given 2 - 3 times a week, for a total of 8 - 12 sessions.

Investigators are testing a procedure called slow repetitive transcranial magnetic stimulation (rTMS), which affects brain activity in the cerebral cortex. The procedure uses an electromagnet placed on the scalp to administer magnetic stimulation to the brain’s cerebral cortex. This region of the brain appears to be associated with auditory hallucinations. A 2007 review of 15 clinical trials indicated that rTMS may be an effective treatment for auditory hallucinations. Further research is underway.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.mentalhealth.samhsa.gov -- National Mental Health Information Center
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.narsad.org -- National Alliance for Research on Schizophrenia and Depression
www.psych.org -- American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.world-schizophrenia.org -- World Fellowship for Schizophrenia and Allied Disorders
www.schizophrenia.com -- Information resources and research news

References

Aleman A, Sommer IE, Kahn RS. Efficacy of slow repetitive transcranial magnetic stimulation in the treatment of resistant auditory hallucinations in schizophrenia: a meta-analysis. J Clin Psychiatry. 2007 Mar;68(3):416-21.

Crespo-Facorro B, Pérez-Iglesias R, Ramirez-Bonilla M, Martínez-García O, Llorca J, Luis Vázquez-Barquero J. A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis. J Clin Psychiatry. 2006 Oct;67(10):1511-21.

Lieberman JA. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: efficacy, safety and cost outcomes of CATIE and other trials. J Clin Psychiatry. 2007 Feb;68(2):e04.

Marder SR, West B, Lau GS, et al. Aripiprazole effects in patients with acute schizophrenia experiencing higher or lower agitation: a post hoc analysis of 4 randomized, placebo-controlled clinical trials. J Clin Psychiatry. 2007 May;68(5):662-8.

Mathews M, Muzina DJ. Atypical antipsychotics: new drugs, new challenges. Cleve Clin J Med. 2007 Aug;74(:597-606.

McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry. 2007 Jul;164(7):1050-60.

Morrens M, Hulstijn W, Sabbe B. Psychomotor slowing in schizophrenia. Schizophr Bull. 2007 Jul;33(4):1038-53. Epub 2006 Nov 8.

Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68 Suppl 1:20-7.

Schultz SH, North SW, Shields CG. Schizophrenia: a review. Am Fam Physician. 2007 Jun 15;75(12):1821-9.

Swartz MS, Perkins DO, Stroup TS, et al. Effects of antipsychotic medications on psychosocial functioning in patients with chronic schizophrenia: findings from the NIMH CATIE study. Am J Psychiatry. 2007 Mar;164(3):428-36.

Torrey EF, Bartko JJ, Lun ZR, Yolken RH. Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull. 2007 May;33(3):729-36. Epub 2006 Nov 3.

A.D.A.M. Copyright

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Anxiety disorders

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, duloxetine (Cymbalta) was approved for treatment of generalized anxiety disorder. Duloxetine is a dual inhibitor antidepressant.

Anxiety Disorders Under-Recognized and Under-Treated

About 41% of patients with an anxiety disorder do not receive any treatment, indicates a 2007 study in the Annals of Internal Medicine. Anxiety disorders can interfere with daily functioning, and problems worsen when people have more than one type of anxiety disorder. The study’s researchers recommend that screening for anxiety become a regular part of office visits in the same way that primary care doctors screen patients for depression.

Antidepressants and Children

The benefits of antidepressants for treating pediatric anxiety disorders appear to outweigh the risks for suicide, according to a 2007 review in the Journal of the American Medical Association. Researchers also found that antidepressants did not work as well for treating obsessive compulsive disorder compared to other types of anxiety disorders. This review was the largest to date of antidepressant use in children and adolescents. Most doctors recommend cognitive behavioral therapy as the first treatment approach for childhood anxiety disorders.

Psychological Therapies for Post-Traumatic Stress Disorder

Specially designed psychotherapies -- such as trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, and stress management -- are the most effective therapies for patients with post-traumatic stress disorder, according to a 2007 review in the Cochrane Database.

Introduction

Fear and stress reactions are essential for human survival. They enable people to pursue important goals and to respond appropriately to danger. In a healthy individual, the stress response (fight, fright, or flight) is provoked by a genuine threat or challenge and is used as a spur for appropriate action.

An anxiety disorder, however, involves an excessive or inappropriate state of arousal characterized by feelings of apprehension, uncertainty, or fear. The word is derived from the Latin, angere, which means to choke or strangle. The anxiety response is often not attributable to a real threat. Nevertheless it can still paralyze the individual into inaction or withdrawal. An anxiety disorder persists, while a healthy response to a threat resolves, once the threat is removed.

Anxiety disorders have been classified according to the severity and duration of their symptoms and specific behavioral characteristics. Categories include:

Generalized anxiety disorder (GAD), which is long lasting and low-grade
Panic disorder, which has more dramatic symptoms
Phobias
Obsessive-compulsive disorder (OCD)
Post-traumatic stress disorder (PTSD)
Separation anxiety disorder (which is almost always seen in children)

GAD and panic disorder are the most common. Anxiety disorders are usually caused by a combination of psychological, physical, and genetic factors, and treatment is, in general, very effective.

Generalized anxiety disorder (GAD) is the most common anxiety disorder. It affects about 5% of Americans over the course of their lifetimes. It is characterized by the following:

A more-or-less constant state of worry and anxiety, which is out of proportion to the level of actual stress or threat in their lives.
This state occurs on most days for more than 6 months despite the lack of an obvious or specific stressor. (It worsens with stress, however.)
It is very difficult to control worry. For a clear diagnosis of GAD, the specific worries should be differentiated from those that would define other anxiety disorders, such as fear of panic attacks or appearing in public. Moreover, they are not obsessive like people with obsessive-compulsive disorder. (It should be noted, however, that over half of those with GAD also have another anxiety disorder or depression.)
Patients with anxiety may experience physical symptoms (such as gastrointestinal complaints) in addition to, or even in place of, mental worries. (This latter case may be more common in people from non-Western cultures such as those with Asian backgrounds.)
People with GAD tend to be unsure of themselves, overly perfectionist, and conforming.

Given these conditions, a diagnosis of GAD is confirmed if three or more of the following symptoms are present (only one for children) on most days for 6 months:

Being on edge or very restless
Feeling tired
Having difficulty with concentration
Being irritable
Having muscle tension
Experiencing disturbed sleep

Symptoms should cause significant distress and impair normal functioning and not be due to a medical condition, another mood disorder, or psychosis. It should be noted that pure GAD is uncommon. It typically occurs with other mood disorders (anxiety or depression) or substance use.

Panic disorder is characterized by periodic attacks of anxiety or terror (panic attacks). They usually last 15 - 30 minutes, although residual effects can persist much longer. The frequency and severity of acute states of anxiety determine the diagnosis. (It should be noted that panic attacks can occur in nearly every anxiety disorder, not just panic disorder. In other anxiety disorders, however, there is always a cue or specific trigger for the attack.) A diagnosis of panic disorder is made under the following conditions:

A person experiences at least two recurrent, unexpected panic attacks.
For at least a month following the attacks, the person fears that another will occur.

Symptoms of a Panic Attack. During a panic attack a person feels intense fear or discomfort with at least four or more of the following symptoms:

Rapid heart beat
Sweating
Shakiness
Shortness of breath
A choking feeling or a feeling of being smothered
Dizziness
Nausea
Feelings of unreality
Numbness
Either hot flashes or chills
Chest pain
A fear of dying
A fear of going insane

Women may be more likely than men to experience shortness of breath, nausea, and feelings of being smothered. More men than women have sweating and abdominal pain. Panic attacks that include only one or two symptoms, such as dizziness and heart pounding, are known as limited-symptom attacks. These may be either residual symptoms after a major panic attack or precursors to full-blown attacks. (It should be noted that panic attacks can also accompany other anxiety disorders, such as phobias and post-traumatic stress disorder. In such cases, however, additional characteristics differentiate these disorders from panic disorder.)

Frequency of Panic Attacks. Frequency of attacks can vary widely. Some people have frequent attacks (for example, every week) that occur for months; others may have clusters of daily attacks followed by weeks or months of remission.

Triggers of Panic Attacks. Panic attacks may occur spontaneously or in response to a particular situation. Recalling or re-experiencing even harmless circumstances surrounding an original attack may trigger subsequent panic attacks.

Phobias, manifested by overwhelming and irrational fears, are common. In most cases, people can avoid or at least endure phobic situations, but in some cases, as with agoraphobia, the anxiety associated with the feared object or situation can be incapacitating.

Agoraphobia. Agoraphobia has been somewhat misleadingly described as fear of open spaces, the term having been derived from the Greek word agora, meaning outdoor marketplace. In its severest form, agoraphobia is characterized by a paralyzing terror of being in places or situations from which the patient feels there is neither escape nor accessible help in case of an attack. (One patient described the terror of going outside as opening a door onto a landscape filled with snakes.) Consequently, people with agoraphobia confine themselves to places in which they feel safe, usually at home. The patient with agoraphobia often makes complicated plans in order to avoid confronting feared situations and places.

Social Phobia. Social phobia, also known as social anxiety disorder, is the fear of being publicly scrutinized and humiliated and is manifested by extreme shyness and discomfort in social settings. This phobia often leads people to avoid social situations and is not due to a physical or mental problem (such as stuttering, acne, or personality disorders). The incidence of social phobia is about 13% and has been termed "the neglected anxiety disorder" because it is often not properly diagnosed.

The associated symptoms vary in intensity, ranging from mild and tolerable anxiety to a full-blown panic attack. (Unlike a panic attack, however, social phobia is always directly related to a social situation.) Symptoms include sweating, shortness of breath, pounding heart, dry mouth, and tremor.

The disorder may be further categorized as generalized or specific social phobia:

Generalized social phobia is the fear of being humiliated in front of other people during nearly all social situations. People with this subtype are the most socially impaired and also the most likely to seek treatment.
Specific social phobia usually involves a phobic response to a specific event. Performance anxiety ("stage fright") is the most common specific social phobia and occurs when a person must perform in public. These patients usually feel comfortable in informal social situations.

Children with social anxiety develop symptoms in settings that include their peers, not just adults, and they may include tantrums, blushing, or not being able to speak to unfamiliar people. These children should be able to have normal social relationships with familiar people, however.

Specific Phobias. Specific phobias (formerly simple phobias) are an irrational fear of specific objects or situations. Specific phobias are among the most common medical disorders. Most cases are mild and not significant enough to require treatment.

The most common phobias are fear of animals (usually spiders, snakes, or mice), flying (pterygophobia), heights (acrophobia), water, injections, public transportation, confined spaces (claustrophobia), dentists (odontiatophobia), storms, tunnels, and bridges.

When confronting the object or situation, the phobic person experiences panicky feelings, sweating, avoidance behavior, difficulty breathing, and a rapid heartbeat. Most phobic adults are aware of the irrationality of their fear, and many endure intense anxiety rather than disclose their disorder.

Obsessive-compulsive disorder (OCD) has been described as hiccups of the mind. OCD is time-consuming, distressing, and can disrupt normal functioning. Much research suggests that a critical feature in this disorder is an overinflated sense of responsibility, in which the patient's thoughts center around possible dangers and an urgent need to do something about it.

Obsessions are recurrent or persistent mental images, thoughts, or ideas. The obsessive thoughts or images can range from mundane worries about whether one has locked a door to bizarre and frightening fantasies of behaving violently toward a loved one.
Compulsive behaviors are repetitive, rigid, and self-directed routines that are intended to prevent the manifestation of an associated obsession. Such compulsive acts might include repetitive checking for locked doors or unlit stove burners or calls to loved ones at frequent intervals to be sure they are safe. Some people are compelled to wash their hands every few minutes or to spend inordinate amounts of time cleaning their surroundings in order to subdue the fear of contagion.

Over half of OCD-sufferers have obsessive thoughts without the ritualistic compulsive behavior. Although individuals recognize that the obsessive thoughts and ritualized behavior patterns are senseless and excessive, they cannot stop them in spite of strenuous efforts to ignore or suppress the thoughts or actions. OCD often accompanies depression or other anxiety disorders. There is some evidence that the symptoms improve over time and that nearly half will eventually recover completely or have only minor symptoms.

Symptoms in children may be mistaken for behavioral problems (taking too long to do homework because of perfectionism, refusing to perform a chore because of fear of germs). Children do not usually recognize that their obsessions or compulsions are excessive.

Associated Obsessive Disorders. Certain other disorders that may be part of, or strongly associated with, the OCD spectrum include the following:

Body dysmorphic disorder (BDD). In BDD, people are obsessed with the belief that they are ugly, or part of their body is abnormally shaped.
Hypochondriasis. People who have hypochondiasis have an excessive fear of having a serious disease.
Anorexia nervosa. OCD frequently accompanies this eating disorder, where the compulsive behavior focuses on food restriction and thinness.
Trichotillomania. People with trichotillomania continually pull their hair, leaving bald patches.
Tourette syndrome. Symptoms of Tourette syndrome include jerky movements, tics, and uncontrollably uttering obscene words.

Obsessive-Compulsive Personality. OCD should not be confused with obsessive-compulsive personality, which defines certain character traits (being a perfectionist, excessively conscientious, morally rigid, or preoccupied with rules and order). These traits do not necessarily occur in people with obsessive-compulsive disorder.

Post-traumatic stress disorder (PTSD) is a severe, persistent emotional reaction to a traumatic event that severely impairs one’s life. It is classified as an anxiety disorder because of its symptoms. Not every traumatic event leads to PTSD, however. There are two criteria that must be present to qualify for a diagnosis of PTSD:

The patient must have directly experienced, witnessed, or learned of a life-threatening or seriously injurious event.
The patients' response is intense fear, helplessness, or horror. Children may behave with agitation or with disorganized behavior.

Triggering Events. PTSD is triggered by violent or traumatic events that are usually outside the normal range of human experience. There is some evidence that events most likely to trigger PTSD are those that involve deliberate and destructive behavior (murder, rape) and those that are prolonged or physically challenging. Such events include, but are not limited to, experiencing or witnessing sexual assaults, accidents, military combat, natural disasters (such as earthquakes), or unexpected deaths of loved ones. PTSD may also occur in people who have serious illness and receive aggressive treatments or who have close family members or friends with such conditions.

Symptoms of PTSD. There are three basic sets of symptoms associated with PTSD. They may begin immediately after the event or can develop up to a year afterward:

Re-experiencing. In such cases, patients persistently re-experience the trauma in at least one of the following ways: in recurrent images, thoughts, flashbacks, dreams, or feelings of distress at situations that remind them of the traumatic event. Children may engage in play, in which traumatic events are enacted repeatedly.
Avoidance. Patients may avoid reminders of the event, such as thoughts, people, or any other factors that trigger recollection. They tend to have an emotional numbness, a sense of being in a daze or of losing contact with their own identity or even external reality. They may be unable to remember important aspects of the event.
Increased Arousal. This includes symptoms of anxiety or heightened awareness of danger (sleeplessness, irritability, being easily startled, or becoming overly vigilant to unknown dangers).

To further qualify for a diagnosis of PTSD, patients must have at least one symptom in the re-experiencing category, three avoidance symptoms, and two arousal symptoms. Symptoms are chronic (3 months or more). Symptoms should also not be associated with alcohol, medications, or drugs and should not be intensifications of a pre-existing psychological disorder.

Acute Stress Disorder. Experts have identified a syndrome called acute stress disorder, in which symptoms of PTSD occur within 2 days to 4 weeks after the traumatic event. Acute stress disorder can accurately identify up to 94% of victims at risk for PTSD. Between 50 - 80% of these patients actually develop the more chronic and serious disorder. In other words, it is very sensitive for identification of those at highest danger for PTSD but less successful in determining specifically who will or will not recover emotionally.

Long-Term Outlook. The long-term impact of a traumatic event is uncertain. In one study of people who survived a mass killing spree in Texas, less than half of those who suffered PTSD (28% of all survivors) had recovered after a year. In another study, PTSD became chronic in 46% of the subjects. In fact, PTSD may cause physical changes in the brain, and in some cases the disorder can last a lifetime.

Separation anxiety disorder almost always occurs in children. It is suspected in children who are excessively anxious about separation from important family members or from home. For a diagnosis of separation anxiety disorder, the child should also exhibit at least three of the following symptoms for at least 4 weeks:

Extreme distress from either anticipating or actually being away from home or being separated from a parent or other loved one
Extreme worry about losing or about possible harm befalling a loved one
Intense worry about getting lost, being kidnapped, or otherwise separated from loved ones
Frequent refusal to go to school or to sleep away from home
Physical symptoms such as headache, stomach ache, or even vomiting, when faced with separation from loved ones

Separation anxiety often disappears as the child grows older, but if not addressed, it may lead to panic disorder, agoraphobia, or combinations of anxiety disorders.

Studies suggest that an imbalance of certain substances called neurotransmitters (chemical messengers in the brain) may contribute to anxiety disorders. The neurotransmitters targeted in anxiety disorders are gamma-aminobutyric acid (GABA), serotonin, dopamine, and epinephrine. Serotonin appears to be specifically important in feelings of well-being, and deficiencies are highly related to anxiety and depression.

Examples of study findings on some neurotransmitters are:

Abnormalities in the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin may have a particular role in susceptibility to generalized anxiety disorder. GABA helps prevent nerve cells from over-firing and serotonin is a brain chemical important in feelings of well-being.
Serotonin is a major player in OCD.
Changes in serotonin and dopamine have been observed in social phobia.
People with post-traumatic stress disorder have abnormalities in stress hormones (cortisol) and neurotransmitters associated with stress (epinephrine and norepinephrine). Such imbalances could account for the higher anxiety levels and a tendency to startle easily after a threat in people with PTSD.
Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety by causing changes in serotonin levels.

The best way to envision the brain's response to a threat is to imagine a primal situation, such as being chased by a bear.

The Brain's Response to Acute Stress. In response to seeing the bear, a part of the brain called the hypothalamic-pituitary-adrenal (HPA) system is activated.

Release of Steroid Hormones and the Stress Hormone Cortisol. The HPA systems trigger the production and release of steroid hormones (glucocorticoids), including the primary stress hormone cortisol. Cortisol is very important in marshaling systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines and Activation of the Amygdala. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate the amygdala, a small structure deep in the brain, which regulates control of major emotional activities, including anxiety, depression, aggression, and affection. In fact, the amygdala is sometimes known as the "fear" center.

Effects on Long- and Short-Term Memory. During the stressful event, catecholamines also suppress activity in areas at the front of the brain concerned with short-term memory, concentration, inhibition, and rational thought. This sequence of mental events allows a person to react quickly to the bear, either to fight or to flee from it. (It also hinders the ability to handle complex social or intellectual tasks and behaviors during that time.)

On the other hand, neurotransmitters at the same time signal the hippocampus (a nearby area in the brain) to store the emotionally loaded experience in long-term memory. In primitive times, this brain action would have been essential for survival, since long-lasting memories of dangerous stimuli (the large bear) would be critical for avoiding such threats in the future.

Response by the Heart, Lungs, and Circulation to Acute Stress. The stress response also affects the heart, lungs, and circulation:

As the bear comes closer, the heart rate and blood pressure increase instantaneously.
Breathing becomes rapid and the lungs take in more oxygen.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen throughout the body. Blood flow may actually increase 300 - 400%, priming the muscles, lungs, and brain for added demands.

The Immune System's Response to Acute Stress. The effect on the immune system from confrontation with the bear is similar to marshaling a defensive line of soldiers to potentially critical areas. The steroid hormones dampen parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be redistributed. These immune-boosting troops are sent to the body’s front lines where injury or infection is most likely, such as the skin, the bone marrow, and the lymph nodes.

The Acute Response in the Mouth and Throat. As the bear gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The Skin's Response to Acute Stress. The stress effect diverts blood flow away from the skin to support the heart and muscle tissues. (This also reduces blood loss in the event that the bear catches up.) The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Metabolic Response to Acute Stress. Stress shuts down digestive activity, a nonessential body function during short-term periods of physical exertion or crisis.

The Relaxation Response: the Resolution of Acute Stress. Once the threat has passed and the effect has not been harmful (the bear has not eaten or seriously wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also normalize.

Causes

A person's genetics, biochemistry, environment, history, and psychological profile all seem to contribute to the development of anxiety disorders. Most people with these disorders seem to have a biological vulnerability to stress, making them more susceptible to environmental stimuli than the rest of the population.

Abnormalities in the Brain. Scientists are using imaging techniques, particularly magnetic resonance imaging (MRI), to identify different areas of the brain associated with anxiety responses.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI can give a three-dimensional depiction of the brain, making location of problems such as tumors or aneurysms more precise.

Important research in anxiety disorders is focusing on changes in the amygdala, which is sometimes referred to as the "fear center." This part of the brain regulates fear, memory, and emotion and coordinates these resources with heart rate, blood pressure, and other physical responses to stressful events. Some evidence suggests that the amygdala in people with anxiety disorders is highly sensitive to novel or unfamiliar situations and reacts with a high stress response.

Obsessive-compulsive disorder (OCD) is the anxiety disorder most strongly associated with specific brain dysfunction. For example, abnormalities in a specific pathway of nerves have been linked to OCD, attention deficit disorder, and Tourette syndrome. The symptoms of the three disorders are similar and they often coexist.

A number of imaging studies have reported less volume in the hippocampus in people with post-traumatic stress disorder. This important region is related to emotion and memory storage.

The influence of the family on anxiety is complicated by both genetic and psychological factors.

Panic Disorder and Family Influence. Certain psychodynamic theories suggest, and a few studies support the idea, that some people may develop panic disorder if they cannot resolve the early childhood conflict of dependence vs. independence. In one study, for example, young adults who had experienced childhood anxiety were more likely to live with their parents until their early to mid-twenties. Many people with panic disorder perceive their parents as being extremely controlling and overly protective while showing little actual affection.

Phobias and Family Influence. Several studies show a strong correlation between a parent's fears and those of the offspring. Although an inherited trait may be present, some researchers believe that many children can "learn" fears and phobias, just by observing a parent or loved one's phobic or fearful reaction to an event. People who have social phobias and severe agoraphobia generally report less parental affection and more strictness, overprotection, and encouragement of dependence than those without these disorders.

Obsessive-Compulsive Disorder and Family Influence. One study found that parental influence played no part in obsessive-compulsive disorder if the OCD patient was also not suffering from depression. However, depression coexists in two-thirds of OCD patients, and in the study patients who had both OCD and depression reported lower levels of parental care and overprotectiveness.

Traumatic events generally trigger anxiety disorders in individuals who are susceptible to them because of psychological, genetic, or biochemical factors. The clearest example is post-traumatic stress disorder. Specific traumatic events in childhood, particularly those that threaten family integrity, such as spousal or child abuse, can also lead to other anxiety and emotional disorders. Some individuals may even have a biological propensity for specific phobias, for instance of spiders or snakes, that have been triggered and perpetuated after a single exposure.

The acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a term for an autoimmune condition associated with group A streptococcal infection in children (the cause of "strep throat" and rheumatic fever). Children with PANDAS develop tic-related disorders, including OCD and Tourette syndrome. In such cases, the OCD symptoms develop abruptly soon after the infection. It is unlikely to be an important cause of OCD.

Risk Factors

As many as 25% of all American adults experience intense anxiety sometime in their lives. The prevalence of true anxiety disorders is much lower, although they are still the most common psychiatric conditions in the United States and affect more than 20 million Americans.

Gender. With the exception of obsessive-compulsive disorder (OCD), women have twice the risk for most anxiety disorders as men. A number of factors may increase the reported risk in women, including cultural pressures to meet everyone else's needs except their own, and fewer self-restrictions on reporting anxiety to doctors.

Age. In general, phobias, OCD and separation anxiety show up early in childhood, while social phobia and panic disorder are often diagnosed during the teen years. Studies suggest that 3 - 5% of children and adolescents have some anxiety disorder. Children and adolescents who have an anxiety disorder are at risk of later developing other anxiety disorders, depression, and substance abuse.

Personality Factors. Children's personalities may indicate higher or lower risk for future anxiety disorders. For example, research suggests that extremely shy children and those likely to be the target of bullies are at higher risk for developing anxiety disorders later in life. Children who cannot tolerate uncertainty tend to be worriers, a major predictor of generalized anxiety. In fact, such traits may be biologically based and due to a hypersensitive amygdala -- the "fear center" in the brain.

Family History and Dynamics. Anxiety disorders tend to run in families. Genetic factors may play a role in some cases, but family dynamics and psychological influences are also often at work.

Social Factors. Several studies have reported a significant increase in anxiety levels in children and college students in the past two decades compared to children in the 1950s. In several studies, anxiety was associated with a lack of social connections and a sense of a more threatening environment. It also appears that more socially alienated populations have higher levels of anxiety. For example, a study of Mexican adults living in California reported that native-born Mexican Americans were three times more likely to have anxiety disorders (and even more likely to be depressed) as those who had recently immigrated to the U.S. The longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional Mexican cultural and social ties seemed to protect recently arrived immigrants from mental illness.

Genetic Factors. Up to 50% of people with panic disorder and 40% of patients with generalized anxiety (GAD) have close relatives with the disorder. (About half of GAD patients also have family members with panic disorder, and about 30% have relatives with simple phobias.)

Obsessive-compulsive disorder (OCD) is also strongly related to a family history of the disorder. Close relatives of people with OCD are up to 9 times more likely to develop OCD themselves. Researchers are making progress in identifying specific genetic factors that might contribute to an inherited risk. Of particular interest are genes that regulate specific neurotransmitters (brain chemical messengers), including serotonin and glutamate. Recent research has suggested that the SLC1A1 gene, which is associated with glutamate regulation, may play an important role in early-onset OCD in boys. Research is also beginning to pinpoint regions on specific chromosomes (1, 3, 7, 6, 9, 15) that may contain genes linked to OCD.

However, there are no genetic tests to date that can identify patients at risk for anxiety disorders.

Medical Conditions. Although no causal relationships have been established, certain medical conditions have been associated with panic disorder. They include migraines, obstructive sleep apnea, mitral valve prolapse, irritable bowel syndrome, chronic fatigue syndrome, and premenstrual syndrome.

GAD affects about 1 - 5% of Americans in the course of their lives and is more common in women than in men. Some experts believe that it is underdiagnosed and more common than any other anxiety disorder. It is certainly the most common anxiety disorder among the elderly. GAD usually begins in childhood and often becomes a chronic ailment, particularly when left untreated. Depression in adolescence may be a strong predictor of GAD in adulthood. Depression commonly accompanies this anxiety disorder in any case.

Age and Panic Disorder. Studies indicate that the prevalence of panic disorder among adults is between 1.6 - 2% and is much higher in adolescence, 3.5 - 9%. Panic disorder usually first occurs either in late adolescence or in the mid-30s.

Gender and Panic Disorder. Women have about twice the risk for panic disorder as men. Panic attacks are very common after menopause. In one study, nearly 18% of older women reported panic attacks within a 6-month period, with over half of these attacks being full-blown. They tended to be associated with stressful life events and poor health. The effects of pregnancy on panic disorder appear to be mixed. It seems to improve the condition in some women and worsen it in others.

Obsessive-compulsive disorder occurs equally in men and women, and it affects about 2 - 3% of people over a lifespan. Most cases of OCD first develop in childhood or adolescence, although the disorder can occur throughout the life span.

Social anxiety disorder is currently estimated to be the third most common psychiatric disorder in the U.S. Studies have reported a prevalence of 7 - 12% in Western nations.

Age and Phobias. The onset of social anxiety disorder is usually during the early teenage years.

Gender and Phobias. Women are more likely to develop social anxiety disorder than men, although equal numbers of men and women seek treatment for it. Most people seeking treatment have had symptoms for at least 10 years.

Studies estimate a lifetime risk for PTSD in the U.S. of up to 8%. People exposed to traumatic events, of course, are at highest risk, but many people can go through such events and not experience PTSD. Studies estimate that 6 - 30% or more of trauma survivors develop PTSD, with children and young people being among those at the high end of the range. Women have the twice the risk of PTSD as men.

Furthermore, PTSD can occur in people not directly involved with a traumatic event. For example, 17% of the U.S. population outside New York City reported some symptoms of post-traumatic stress 2 months after the September 11 attack on the World Trade Towers. (In the city itself, where the attack occurred, an estimated 7.5% of New York's population reported PTSD within the month of the event, which declined to 0.6% at 6 months.)

Researchers are trying to determine factors that might increase vulnerability to catastrophic events and put people at risk for develop PTSD. Some studies report the following may be risk factors:

Pre-existing emotional disorder. People who have a history of an emotional disorder, particularly depression, before the traumatic event are at higher risk for PTSD.
Drug or alcohol abuse
A family history of anxiety
A history of abuse, particularly that which threatens family integrity, such as spousal or child abuse. Studies of individuals who had suffered physical or sexual abuse or neglect as children suggest that up to one-third develop PTSD.
An early separation from parents
Lack of social support and poverty
Sleep disorders. Insomnia and excessive daytime sleepiness even within a month after a traumatic event are important predictors for the development of PTSD. One specific sleep disorder -- sleep apnea -- may even intensify symptoms of PTSD, including sleeplessness and nightmares. Sleep apnea occurs when tissues in the upper throat (or airway) collapse at intervals during sleep, thereby blocking the passage of air. In one study, 91% of crime victims with PTSD had either sleep apnea or a lesser condition that partially blocked the airways during sleep. In fact, in one study treatment of sleep apnea eased PTSD. Sleep apnea has also been associated with a risk for panic disorder. [For more information, see In-Depth Report #65: Sleep apnea.]

Complications

Studies consistently report that all types of anxiety disorders can be very debilitating and seriously affect a person’s quality of life.

Depression. Depression is very common in people with an anxiety disorder, and it is sometimes difficult to distinguish one from the other because either or both can be accompanied by anxious feelings, agitation, insomnia, and problems with concentration.

Depression and nearly every anxiety disorder often go hand in hand, in both the young and old. In fact, the lifetime risk for depression in people with anxiety disorders may be higher than 70%. Furthermore, the combination of depression and anxiety is a major risk factor for both substance abuse and suicide. The following are examples of depression in specific anxiety disorders:

Between 50 - 65% of people with panic disorder also have major depression. Some studies have suggested that treating panic disorder early enough may help prevent major depression later on.
More than two-thirds of OCD patients suffer from depression.
Most patients with GAD will experience at least one episode of significant depression and many develop recurrent episodes. In patients with both disorders, GAD usually precedes the onset of depression.
Social anxiety during adolescence or young adulthood has been associated with a higher risk for depression, and the presence of both increases the chances for severe depression.
People with PTSD are four to seven times as likely to be depressed as are people without PTSD.

Bipolar Disorder. Symptoms of panic disorder are very common in people with bipolar disorder (manic-depression). In fact, people with bipolar have 26 times the rate of panic disorder as in the general population. Furthermore, anxiety worsens bipolar disorder. According to one study, anxiety disorders in teenagers were associated with bipolar disorder in adulthood, while manic behavior in adolescence was linked to later anxiety disorders.

Evidence now strongly supports an association between panic disorder and a risk for suicidal thoughts. Studies report that up to 18% of people with panic disorder attempt suicide and up to 38.5% regularly harbor suicidal thoughts, with the risks being higher in people with both panic disorder and depression. One study reported suicide attempts in about 12% of people with social phobias or OCD. If a person has an anxiety disorder and a mood disorders (such as depression), the risk for suicide is even higher.

Suicide is the third most common cause of death among adolescents, and is one of the most devastating events than can happen to a family. Suicide is most commonly associated with depression in young people, but it is also commonly associated with anxiety, psychosis, substance abuse, or impulsivity. More girls attempt suicide but more boys succeed, most often because they choose guns or violent methods while girls tend to overdose, which is more treatable. Nevertheless, unsuccessful attempts are major risk factors for a later suicide. Any expression of suicidal intent should be treated very seriously.

The following are danger signs in young people:

Withdrawal from friends
Sudden decrease in school performance
Loss of interest in activities that were previously pleasurable
Unusual irritability
Unusual changes in sleep or eating habits

In one study, adolescents failed to seek help for suicidal thoughts for the following reasons:

They believed nothing would help.
They were reluctant to tell anyone they had problems.
They thought it was a sign of weakness to seek help.
They did not know where to go.

Parents should not hesitate to seek professional help for their children if they suspect they are thinking about killing themselves. This is a medical emergency and requires immediate treatment.

[For more information on suicide, see In-Depth Report #8: Depression.]

Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Anxiety disorders are highly prevalent among people with alcoholism. Moreover, long-term alcohol use can itself cause biologic changes that may actually produce anxiety and depression.

Risk for Substance Abuse in Specific Anxiety Disorders. The following are some observations on specific anxiety disorders and substance abuse:

Some people with GAD and panic disorders may use alcohol or drugs to self-medicate.
Social phobia appears to pose a particular risk for alcohol abuse. People with this disorder are likely to drink in order to boost confidence. Alcohol itself has no direct beneficial effect on anxiety, but studies suggest that the belief in its effect appears to relieve anxious feelings. (Alcohol or substance abuse is not associated with specific phobias -- such as a fear of flying or spiders.)
Heavy smoking and substance abuse are common in people with PTSD. In adolescents, the disorder not only increases the risk for drug and alcohol use but also for eating disorders.

Studies consistently report that anxiety disorders have negative effects on work and relationships. Some examples:

In one study, more than 10% of patients with GAD missed at least 6 days of work within the previous month.
In a survey of OCD sufferers, 40% reported that they had to stop working because of the disorder. Only 40% worked full-time, while only half were married.
A 2006 study indicated that children with OCD are more likely to be bullied than other children.
Studies report that people with social phobias are less likely to get married, to leave home, and to finish school than those without this disorder. Their outlook worsens if they have other emotional disorders.

Anxiety disorders are associated with many different physical illnesses. Research suggests that people who have both an anxiety disorder and a physical illness have a worse quality of life and greater risk for disability than those who have only a physical illness. Anxiety disorders often tend to occur before the development of physical disorders.

Heart Disease. Anxiety has been associated with several heart problems, including unhealthy cholesterol levels, thicker blood vessels, and high blood pressure. Both anxiety and depression have been associated with a poorer response to treatment in heart patients, including a worse outcome after heart surgery.

Cholesterol is a soft, waxy substance that is present in all parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

Some researchers speculate that intense anxiety might trigger abnormal and dangerous heart rhythms in people with existing heart problems. In other studies, panic disorders, post-traumatic stress disorder, and phobias have been associated with a higher rate of sudden death from cardiac events, including heart attack.

Gastrointestinal Disorders. Anxiety frequently accompanies gastrointestinal conditions. Of note, half the cases of irritable bowel syndrome are associated with anxiety.

Headache. Both tension and migraine headaches are associated with anxiety disorders. One study reported that 32% of people with chronic tension headaches met criteria for anxiety. Similarly, another study reported that young girls with anxiety disorders were three times more likely to have chronic headaches than those without the disorder. (Headaches in both studies were also strongly associated with depression.)

Respiratory Problems. Studies report an association between anxiety in patients with obstructive lung conditions (asthma, emphysema, and chronic bronchitis) and more frequent relapses.

Obesity. Anxiety disorders may lead to obesity, and the reverse may also be true. A 2006 study suggested that anxiety disorders and depression in childhood may lead to higher body mass index (BMI) in adult women (but not men). Another 2006 study indicated that obesity is associated with a 25% increased risk of developing anxiety and mood disorders.

Allergic Conditions. Anxiety disorders are associated with numerous allergic conditions including hay fever, eczema, hives, food allergies, and conjunctivitis.

Other Conditions. Other physical conditions associated with anxiety disorders include thyroid problems and arthritis.

People with obsessive-compulsive disorders can experience skin problems from excessive washing, injuries from repetitive physical acts, and hair loss from repeated hair pulling (behavior known as trichotillomania).

Effect of PTSD on the Brain. Studies are reporting that PTSD is associated with shrinkage in the hippocampus, the part of the brain important for memory and learning. Some animal studies indicate that such damage may result from long-term exposure to cortisol, the major stress hormone. In one study, people who had suffered severe trauma scored 40% lower in tests of verbal memory than did the general population. There was no difference in IQ or in scores of other types of memory. Some studies suggest that exposure to chronic stress, common in PTSD patients, may even compromise the function of the brain’s receptors for anti-anxiety medication. On the other hand, a small hippocampal volume may itself increase stress hormone levels, so people with genetically smaller hippocampi may be susceptible to PTSD.

Effects of PTSD on Health. Studies of military veterans who have endured major traumatic events have found a higher risk for health problems. One study of Vietnam veterans reported that PTSD was associated with greater physical limitations, poorer physical health, and a lower quality of life than was found in the general population, regardless of other accompanying emotional or medical disorders. In another study of these veterans, PTSD sufferers had twice the risk for abnormal heart rhythms and four times the risk of a heart attack compared to men without PTSD.

Evidence suggests an association between anxiety in children and recurrent stomach aches. Anxiety has been associated with a higher risk for sleep disorders in children, such as frequent nightmares, restless legs syndrome, and bruxism (grinding and gnashing of the teeth during sleep).

Diagnosis

A physical examination and medical and personal history is essential. Because anxiety accompanies so many medical conditions, some serious, it is extremely important for the doctor to uncover any medical problems or medications that might underlie or be masked by an anxiety attack.

The patient should describe any occurrence of anxiety disorders or depression in the family and mention any other contributing factors, such as excessive caffeine use, recent life changes, or stressful events.

It is very important to be honest with your doctor about all conditions, including excessive drinking, substance abuse, or other psychological or mood states that might contribute to, or result from, the anxiety disorder.

Diagnosing children with an anxiety disorder can be very difficult, since anxiety often results in disruptive behaviors that overlap with attention-deficit hyperactivity or oppositional disorder. Other conditions with symptoms similar to anxiety disorders include pervasive developmental disorders such Asperger syndrome, learning disabilities, bipolar disorder, and depression. Many children have anxiety disorder and a co-occurring condition, which should be treated along with anxiety.

People with anxiety disorders are more likely to see a family doctor before a mental health specialist, since their symptoms are often physical. Symptoms can include muscle tension, trembling, twitching, aching, soreness, cold and clammy hands, dry mouth, sweating, nausea or diarrhea, or urinary frequency. Anxiety attacks can mimic or accompany nearly every acute disorder of the heart or lungs, including heart attacks and angina (chest pain). In fact, nearly all individuals with panic disorders are convinced that their symptoms are physical and possibly life-threatening.

Heart Problems. Studies suggest that up to a third of patients entering the emergency room with chest pain and who are low-to-moderate risk for a heart attack are actually suffering from panic attacks. It is often difficult even for specialists to distinguish between heart conditions and a panic attack:

Women who are having an actual heart attack or acute heart problem are much more likely to be misdiagnosed as having an anxiety attack than are men with similar symptoms.
Mitral valve prolapse, a common and usually mild heart problem, may have symptoms that are nearly identical to those of panic disorder. The two conditions, in fact, frequently occur together.

Mitral valve prolapse is a disorder in which the mitral valve does not close properly when the heart contracts. When the valve does not close properly it allows blood to backflow into the left atrium. Some symptoms can include palpitations, chest pain, difficulty breathing after exertion, fatigue, cough, and shortness of breath while lying down.

People with a heart-rhythm disturbance called paroxysmal supraventricular tachycardia have many of the same symptoms as those with panic attacks.

Asthma. Asthma attacks and panic attacks have similar symptoms and can also coexist.

Hyperthyroidism. Hyperthyroidism can cause many of the same symptoms of generalized anxiety disorder and must be ruled out.

Click the icon to see an image of hyperthyroidism.

Epilepsy. The symptoms of partial seizures and panic attacks often overlap.

Other Medical Conditions. In addition, anxiety-like symptoms are seen in many other medical problems, including hypoglycemia, recurrent pulmonary emboli, and adrenal-gland tumors. Women can also experience intense anxiety attacks with hot flashes during menopause.

Medication Side Effects. Many drugs, including some for high blood pressure, diabetes, and thyroid disorders, can produce symptoms of anxiety. Withdrawal from certain drugs, often those used to treat sleep disorders or anxiety, can also precipitate anxiety reactions.

Substance Abuse. People with anxiety disorders often drink alcohol or abuse drugs in order to conceal or eliminate symptoms, but substance abuse and dependency can also cause anxiety. In addition, withdrawal from alcohol can produce physiologic symptoms similar to panic attacks. Clinicians often have difficulty determining whether alcoholism or anxiety is the primary disorder. Overuse of caffeine or abuse of amphetamines can cause symptoms resembling a panic attack.

Clinicians use various screening tests to determine the causes, type, severity, and frequency of anxiety. Such tests include the Hamilton Anxiety Rating Scale, the Beck Anxiety Inventory, the Penn State Worry Questionnaire, and the Yale-Brown Obsessive Compulsive Scale.

Treatment

Anxiety disorders require treatment. Simply trying to talk oneself out of anxiety is as futile as trying to talk oneself out of a heart or stomach problem. Most anxiety disorders, especially phobias, respond well to treatment. They may, however, require long-term treatment. Many patients have a recurrence and may require additional medications. Nevertheless, most patients do not receive appropriate care for anxiety disorders. Many patients do not receive any treatment at all.

The standard current approach to most anxiety disorders is a combination of cognitive-behavioral therapy (CBT) and an antidepressant medication. A selective serotonin reuptake inhibitor (SSRI) is typically the first choice, with the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor) an alternative. If patients do not respond to these drugs, tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs) may be helpful. Benzodiazepines may be recommended for patients who are not helped by antidepressants. A healthy lifestyle that includes exercise, adequate rest, and good nutrition can also help to reduce the impact of anxiety.


Anxiety Disorder	Medications	Cognitive-Behavioral Therapy (CBT) and other Non-Drug Therapies
Generalized Anxiety Disorder	Antidepressants, benzodiazepines, and buspirone are helpful but have varying side effects. Investigational drugs include pregabalin and other anticonvulsants.	Cognitive-behavioral therapy or anxiety management therapy. Anxiety management therapy involves education, relaxation training, and exposure to anxiety-provoking stimuli but does not include cognitive restructuring.
Panic Attacks	SSRIs are treatment of choice. If patients do not respond to SSRIs, short-term treatment with a benzodiazepine may be used, or patients may switch to another type of antidepressant such as venlafaxine or tricyclics.	Cognitive-behavioral therapy, provided in 12 - 16 sessions over 3 - 4 months, focuses on recreating fear symptoms and helping patients change their response to them.
Social Anxiety Disorder	SSRIs or venlafaxine are first-line drug treatments. Benzodiazepines may help patients who do not respond to these antidepressants. In severe cases, an MAOI antidepressant may be prescribed. Anticonvulsants such as gabapentin (Neurontin) and pregabalin (Lyrica) are being investigated.	Cognitive-behavioral therapy can help improve symptoms after 6 - 12 weeks.
Obsessive-Compulsive Disorder	SSRIs are the first choice for adults. Clomipramine (a tricyclic antidepressant) is an alternative for adult patients who do not respond to SSRIs. For children, SSRIs do not seem to work as well for OCD as for other types of anxiety disorders.	Cognitive-behavioral therapy is the first treatment choice for children. For adults, either CBT or drug therapy may be offered as initial treatment. CBT techniques focus on exposure and response prevention (ERP).
Post-Traumatic Stress Disorder	Antidepressants, particularly SSRIs (sertraline and paroxetine approved for PTSD). The atypical antipsychotic olanzapine may be added to an antidepressant for patients who do not respond to a SSRI alone.	Trauma-focused psychological treatments include exposure therapy, trauma-focused cognitive therapy, and eye movement desensitization and reprocessing.
Note: For anxiety disorders in adults, the most effective treatments are usually combinations of drugs and CBT techniques. For children, CBT is usually the first treatment.

Medications

Selective serotonin-reuptake inhibitors (SSRIs), or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor), are the primary first-line treatment for anxiety disorders. For patients who are not helped by these drugs, benzodiazepines, either alone or in combination with an antidepressant, may be prescribed. Other types of antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), may also be used to treat patients with severe or chronic forms of anxiety disorders.

Drug therapies for anxiety disorders work best in combination with cognitive behavioral therapy.

Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro).

SSRIs can cause agitation, nausea, and diarrhea. Sexual function side effects include low sex drive, inability to have an orgasm, and impotence. Over time, many SSRI-treated patients gain weight, although the degree of weight gain varies depending on the drug. Elderly people taking these drugs should take the lowest effective dose possible, and those with heart problems should be monitored closely.

There have been many concerns about SSRIs and increased risk for suicidal behavior. Both adults and children who are treated with SSRIs should be carefully monitored for any worsening of depressive symptoms or changes in behavior. This is especially important during the first few months of antidepressant treatment.

Paroxetine has been linked to heart-related birth defects when women took this drug during the first trimester of pregnancy. Experts are also advising caution in prescribing other types of SSRIs to pregnant women. While certain SSRIs may carry increased risks for some specific type of rare birth defects, research suggests that the overall risks are minimal. Still, women who are pregnant or who are considering becoming pregnant should discuss the potential risks of these drugs with their doctors.

Serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs are known as dual inhibitors because they work on two neurotransmitters -- norepinephrine and serotonin. Venlafaxine (Effexor) is an SNRI that is approved for treatment of generalized anxiety disorder, social anxiety disorder, and panic disorder in adults. (It is not approved for children.) As with many SSRIs, venlafaxine impairs sexual function. Venlafaxine can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. Some patients report severe withdrawal symptoms, including dizziness and nausea. This drug has a serious risk for overdose. Venlafaxine should not be taken during the last trimester of pregnancy because the drug can cause complications in newborn infants.

Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. In 2007, it was approved for treatment of generalized anxiety disorder. Side effects are generally mild and include dry mouth, nausea, and sleepiness. Patients with narrow-angle glaucoma or patients with liver or kidney diseases should not take duloxetine. Because duloxetine can cause liver damage, patients who drink large quantities of alcoholic beverages should not take it.

Mitrazapine (Remeron) is another type of SNRI that is sometimes used for treatment of post-traumatic stress disorder and social anxiety disorder.

Tricyclic Antidepressants. Tricyclics are an older type of antidepressant. Tricyclics used for treatment of anxiety disorder include imipramine (Tofranil, for generalized anxiety disorder, panic disorder), nortriptyline (Pamelor, for panic disorder), desipramine (Norpramin, for panic disorder), and clomipramine (Anafranil, for obsessive compulsive disorder). Clomipramine is approved specifically for OCD, but because of its severe side effects it is usually used only if SSRIs have failed to help.

Side effects of TCAs include sleep disturbance, abrupt reduction in blood pressure upon standing, weight gain, sexual dysfunction, and mental disturbance. Elderly patients and those with a history of seizures, cardiac problems, closed-angle glaucoma, and urinary retention or obstruction should be closely supervised when taking tricyclics.

Monoamine Oxidase Inhibitors. Monoamine oxidase inhibitors (MAOIs) are the oldest type of antidepressant. The MAOI phenelzine (Nardil) is sometimes used to treat social anxiety disorder or post-traumatic stress disorder that has not responded to other treatments.

MAOIs commonly cause weight gain, drowsiness, dizziness, sexual dysfunction, and insomnia. Dietary restrictions are the main problem with these drugs. Severe high blood pressure (hypertension) can be brought on by eating certain foods that have a high tyramine content, including cheese, red wine, and processed meats. High blood pressure can also occur when MAOIs are taken with certain drugs, including some common over-the-counter cough medications and decongestants. MAOIs can cause birth defects and should not be taken by pregnant women.

Most serious, fatal reactions can occur when MAOIs and SSRIs or venlafaxine are taken at the same time. There should be at least a 2- to 5-week break if a patient is changing from one type of antidepressant to the other.

Benzodiazepines are safe and effective medications for most anxiety disorders and have been the standard of treatment for years. However, their on-going use has been associated with a high risk for dependency and abuse. Therefore, they have been supplanted in most cases by SSRIs and other newer antidepressants. For anxiety disorders, benzodiazepines are most often used to treat panic disorder, and are sometimes used for social anxiety disorder and generalized anxiety disorder. These drugs include alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan).

Benzodiazepines have many side effects, generally associated with chronic use. The most common are daytime drowsiness and a hung-over feeling. In rare cases, they can cause agitation. They may worsen respiratory problems. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses can be serious, although they are very rarely fatal.

The elderly are more susceptible to side effects and should usually start at half the dose prescribed for younger people. These drugs increase the risk of falling, which can increase the risk for hip fracture in older people. Also of concern are studies showing a high risk of automobile accidents in people who take benzodiazepines. Benzodiazepines taken during pregnancy are associated with birth defects, and they should not be used by pregnant women or by nursing mothers.

Loss of Effectiveness and Dependence. Eventually these drugs can lose their effectiveness with continued use at the same dosage. As a result, patients may want to increase their dosage to prevent anxiety. This causes dependency, which can occur after taking these drugs for several weeks.

Withdrawal and its Treatments. Withdrawal symptoms can be very severe, even in people who rapidly discontinue benzodiazepines after taking them for only 4 weeks. Symptoms include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience stomach distress, sweating, and insomnia, which can last 1 - 3 weeks. The longer the drugs are taken and the higher their dose, the more severe these symptoms can become. Simply tapering off gradually helps about 60% of people stop taking these drugs. Certain medications (anti-seizure drugs, antidepressants, buspirone) may also help with withdrawal.

Azapirones, such as buspirone (BuSpar), act on serotonin receptors called 5-HT(1A). Buspirone appears to work as well as a benzodiazepine for treating generalized anxiety disorder. It usually takes several days to weeks for the drug to be fully effective. It is not useful against panic attacks.

Buspirone does not produce any immediate euphoria or change in sensation, so some people believe, erroneously, that the drug doesn't work. Such qualities result in a very low potential for abuse. In fact, unlike the benzodiazepines, buspirone is not addictive, even with long-term use, so it may be particularly useful for the patient whose anxiety disorder coexists with alcoholism or drug abuse.

Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. Buspirone should not be used with monoamine oxidase inhibitors (MAOIs).

Beta-blockers, including propranolol (Inderal) and atenolol (Tenormin), block the nerves that stimulate the heart to beat faster. They affect only the physiologic symptoms of anxiety (particularly rapid heart rate) and are most helpful for phobias, particularly performance anxiety. They may be taken before entering a situation where anxiety symptoms tend to occur. Beta-blockers are less effective for other forms of anxiety.

Atypical antipsychotics are mostly used for treating schizophrenia, bipolar disorder, and major depressive disorder. Doctors sometimes use the atypical antipsychotic olanzapine (Zyprexa) for treating severe cases of post-traumatic stress disorder. However, olanzapine has severe side effects, including weight gain and increased high blood sugar levels, which can increase the risk for diabetes. [For more information, see In-Depth Report #47: Schizophrenia.]

Pregabalin (Lyrica) and gabapentin (Neurontin) are drugs used to treat seizures and other conditions. Researchers are investigating whether these drugs may be useful for certain anxiety disorders, such as social anxiety disorder and general anxiety disorder. Their exact role in the treatment of anxiety disorders is not clear, however.

Studies indicate that the dietary supplement inositol may have benefits for panic disorder and, possibly, obsessive compulsive disorder. Inositol is part of the vitamin B complex.

Some patients use aromatherapy as a relaxation aid. Aromatherapy is in general safe, but some plant extracts in these formulas have been linked to skin allergies.

There is no evidence supporting the efficacy of valerian, St. John’s wort, or passionflower for treatment of anxiety. The herbal remedy kava has been associated with liver problems and should not be avoided, especially by patients with liver disease or those who use alcohol. Kava can also interact dangerously with medications that are metabolized by the liver.

Other Treatments

The goal of cognitive-behavioral therapy (CBT) is to regain control of reactions to stress and stimuli, thus reducing the feeling of helplessness that often accompanies anxiety disorders. CBT works on the principle that the thoughts that produce and maintain anxiety can be recognized and altered using various techniques that change behavioral responses and eliminate the anxiety reaction. Many studies have shown that a combination of CBT and medication works best for treating anxiety disorders.

A number of CBT approaches work well for treating many types of anxiety disorders. Studies suggest that CBT is also helpful for patients who have additional conditions, such as depression, a second anxiety disorder, or alcohol dependency. (It may take longer to achieve a successful outcome in such cases, however.) CBT is often given along with drug treatment. A study in the Journal of the American Medical Association found that children and adolescents with OCD responded better to CBT alone than the antidepressant setraline (Zoloft) alone, but most patients did best when they were treated with a combination of CBT and sertraline.

Both individual and group treatments work well. (However, people with social phobia may do better in individual sessions.) Several recent studies also indicate that telephone-based behavioral therapy works well for people with OCD, generalized anxiety disorder, and panic disorders.

Anxiety disorders are chronic, however, and recurrence is common. Some studies indicate that 30 - 82% of people with panic disorder and phobias have a recurrence of attacks at an average of 9 months, even after successful short-term therapy. Medications, then, are also generally recommended for most patients.

Basic Cognitive Therapy Techniques. Treatment usually takes about 12 - 20 weeks. The essential goal of cognitive therapy is to understand the realities of an anxiety-provoking situation and to respond to reality with new actions based on reasonable expectations.

First, the patient must learn how to recognize anxious reactions and thoughts as they occur. One way of accomplishing this is by keeping a daily diary that reports the occurrences of anxiety attacks and any thoughts and events associated with them. A patient with OCD, for instance, may record repetitive thoughts.
These entrenched and automatic reactions and thoughts must be challenged and understood. Again, using the OCD example, one approach is to record and play back the words of the repetitive thoughts, over exposing the patient to the thoughts and reducing their effect. One effective approach for patients with generalized anxiety disorder targets their intolerance of uncertainty and helps them develop methods to cope with it.
Patients are usually given behavioral homework assignments to help them change their behavior. For example, a person with generalized social phobia may be asked to buy an item and then return it the next day. As the patient performs this action, they observe any unrealistic fears and thoughts triggered by such an event.
As the patient continues with self-observation, they begin to perceive the false assumptions that underlie the anxiety. For example, OCD patients may learn to recognize that their heightened sense of responsibility for preventing harm in non-threatening situations is not necessary or even useful.
At that point, the patient can begin substituting new ways of coping with the feared objects and situations.

Systematic Desensitization. Systematic desensitization is a specific technique that breaks the link between the anxiety-provoking stimulus and the anxiety response. This treatment requires the patient to gradually confront the object of fear. There are three main elements to the process:

Relaxation training
A list composed by the patient that prioritizes anxiety-inducing situations by degree of fear
The desensitization procedure itself, confronting each item on the list, starting with the least stressful

This treatment is especially effective for simple phobias, social phobias, agoraphobia, and post-traumatic stress syndrome.

Exposure and Response Treatment. Exposure treatment purposefully generates anxiety by exposing the patient repeatedly to the feared object or situation, either literally or using imagination and visualization. It uses the most fearful stimulus first. (This differs from the desensitization process because it does not involve relaxation or a gradual approach to the source of anxiety.)

Exposure treatments are usually known as either flooding or graduated exposure:

Flooding exposes the person to the anxiety-producing stimulus for as long as 1 - 2 hours.
Graduated exposure gives the patient a greater degree of control over the length and frequency of exposures.

In both cases, the patient experiences the anxiety over and over until the stimulating event eventually loses its effect. Combining exposure with standard cognitive therapy may be particularly beneficial. This approach has helped certain patients in most anxiety disorder categories, including post-traumatic stress disorder.

Modeling Treatment. Phobias can often be treated successfully with modeling treatment:

The therapy typically uses an actor who approaches an anxiety-producing object or engages in a fear-provoking activity that is similar to the patient's specific problem. Either a live or videotaped situation may be used, although the live model is considered to be more effective.
The patient observes this event and tries to learn how to behave in a comparable manner.

Other forms of psychotherapy, commonly called emotion-based psychotherapy (EBT), psychodynamic therapy, or "talk" therapy, deal more with childhood roots of anxiety and usually, although not always, require longer treatments. They include interpersonal therapy, supportive psychotherapy, attention intervention, and psychoanalysis. All work is done during the sessions. Some research indicates that such therapies might be more useful for generalized anxiety, which may require more sustained work to process and recover from early traumas and fears. Studies suggest that although emotion-based psychotherapies are not as effective as cognitive-behavioral therapy (CBT) in treating panic disorders, patients tend to stay longer in EBT than in CBT. Some doctors suggest adding elements of EBT to the usual CBT and medication treatments.

Anxiety Management Therapy. Anxiety management therapy is sometimes used as an alternative to CBT for generalized anxiety disorder. It involves patient education, relaxation training, and exposure to anxiety-provoking stimuli but does not include exercises in cognitive retraining.

Relaxation Training. Relaxation techniques use muscle relaxation and mental visualization to help focus attention towards a calming feeling. Some people find meditation helpful.

Breathing Retraining. Breathing retraining techniques may help reduce the physical effects of anxiety. For example, hyperventilation is one of the primary physical manifestations of panic disorders. This involves rapid, tense breathing, resulting in chest pain, dizziness, tingling of the mouth and fingers, muscle cramps, and even fainting. By practicing measured, controlled breathing at the onset of a panic attack, patients may be able to prevent full attacks.

Biofeedback. Biofeedback uses special sensors that allow patients to recognize anxiety states by changes in specific physical functions, such as changes in pulse rate, skin temperatures, and muscle tone. Eventually they learn to modify these changes, which in turn helps relieve anxiety. While commonly used, there are not many rigorous studies showing that biofeedback helps patients reduce or eliminate their symptoms over the long term.

Several types of psychological treatments have been designed specifically for treating patients with PTSD. These approaches include a special type of CBT known as trauma-focused cognitive behavioral therapy (TFCBT), and a psychotherapy treatment called eye movement desensitization and reprocessing (EMDR).

With TFCBT, patients are taught stress management skills. The therapist helps the patient develop a narrative (verbal, written, or artistic) about the traumatic event. Patients may be exposed to reminders about the trauma and are taught how to cope with future reminders. Through the process, the patient learns how to reprocess their thoughts, feelings, and behaviors.

With EMDR, the patient focuses on remembering the traumatic experience while visually following the rhythmic movement of the therapist’s fingers. The patient recounts to the therapist what memories have been provoked during the exercise. EMDR may help patients recall details and sensations that they had blocked out. Through this breakthrough, patients learn how to regain emotional control.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses to target and stimulate specific areas of the brain. Research has particularly focused on possible benefits for obsessive-compulsive behavior. Some studies have found some improvement in mood, but more research is needed to determine its value for reducing anxiety and obsessions.

In 2006, the U.S. National Institutes of Health funded a large study to examine whether deep brain stimulation (DBS) can help patients with OCD. DBS involves implanting tiny stimulators into the brain to block abnormal nerve signals that cause obsessive symptoms. These “brain pacemakers” are approved to treat epilepsy and Parkinson’s disease. Researchers hope that DBS may eventually provide a new treatment option for patients with severe OCD.

A surgical technique called cingulotomy involves interrupting the cingulate gyrus, a bundle of nerve fibers in the front of the brain. It is sometimes used as a last resort for patients with severe OCD. A variation of this procedure using magnetic resonance imaging (MRI) to guide the surgeon has resulted in long-term improvement in about 25 - 33% of OCD patients in whom it is performed. The procedure is generally safe with few serious complications and does not affect intellect or memory.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.adaa.org -- Anxiety Disorders Association of America
www.nami.org -- National Alliance on Mental Illness
www.psych.org -- The American Psychiatric Association
www.apa.org -- The American Psychological Association
www.istss.org -- International Society for Traumatic Stress Studies
www.ncvc.org -- National Center for Victims of Crime
www.ncptsd.va.gov -- National Center for Post-Traumatic Stress Disorders
www.rainn.org -- Rape, Abuse, and Incest National Network
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.ocfoundation.org -- Obsessive Compulsive Foundation

References

Bisson J, Andrew M. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003388.

Bisson JI. Post-traumatic stress disorder. BMJ. 2007 Apr 14;334(7597):789-93.

Connolly SD, Bernstein GA; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2007 Feb;46(2):267-83.

Gale C, Davidson O. Generalised anxiety disorder. BMJ. 2007 Mar 17;334(7593):579-81.

Heyman I, Mataix-Cols D, Fineberg NA. Obsessive-compulsive disorder. BMJ. 2006 Aug 26;333(7565):424-9.

Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001848.

Ipser JC, Carey P, Dhansay Y, Fakier N, Seedat S, Stein DJ. Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005473.

Katon WJ. Clinical practice. Panic disorder. N Engl J Med. 2006 Jun 1;354(22):2360-7.

Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Jul;164(7 Suppl):5-53.

Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007 Mar 6;146(5):317-25.

Saeed SA, Bloch RM, Antonacci DJ. Herbal and dietary supplements for treatment of anxiety disorders. Am Fam Physician. 2007 Aug 15;76(4):549-56.

Schneier FR. Clinical practice. Social anxiety disorder. N Engl J Med. 2006 Sep 7;355(10):1029-36.

Smoller JW, Pollack MH, Wassertheil-Smoller S, et al. Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study. Arch Gen Psychiatry. 2007 Oct;64(10):1153-60.

A.D.A.M. Copyright

adam.com

Herpes simplex

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Symptoms
Transmission
Risk Factors
Complications
Diagnosis
Similar Conditions
Home Remedies and Preventio...
Treatment for Genital Herpe...
Treatment for Oral Herpes...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Herpes Diagnosis

In 2006, the U.S. Centers for Disease Control (CDC) released updated guidelines for diagnosis and management of sexually transmitted diseases.

For diagnosis of genital herpes, the CDC recommends the use of both skin and blood tests.
Blood (or type-specific serologic) tests must be able to detect antibodies to glycoprotein G (gG). According to the CDC, gG serologic tests are much more accurate than other types of blood tests and are the only ones that should be used. These blood tests can help determine whether genital herpes is caused by herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2).
Although HSV-1 has traditionally been the main cause of oral herpes, and HSV-2 the main cause of genital herpes, HSV-1 is now causing up to 50% of all cases of genital herpes. Prognosis may vary depending on the type of virus involved.

Herpes Treatment

Acyclovir (Zovirax), famiciclovir (Famvir), and valacyclovir (Valtrex) are used for episodic treatment (when herpes outbreaks occur) or suppressive treatment (preventing outbreaks). Valacyclovir may be a particularly good choice for reducing the risk of herpes transmission among heterosexual couples when only one partner is infected with HSV-2.
According to a 2007 review of studies involving over 6,000 patients, these drugs are very effective in reducing herpes recurrences.

Herpes and HIV

Treatment of HSV-2 can help reduce HIV levels in women who are infected with both viruses, indicates a study published in 2007 in the New England Journal of Medicine. In the trial, women who received twice-daily valacyclovir therapy for 12 weeks had reduced genital-track shedding of HIV and blood HIV levels compared to women who received placebo. Researchers are now focusing on the major question: Whether treatment of genital herpes can help prevent HIV transmission.

Introduction

Herpes simplex virus (HSV) commonly causes infections of the skin and mucous membranes. Sometimes it can cause more serious infections in other parts of the body. HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years.

Herpes simplex is part of a group of other herpes viruses that include human herpesvirus 8 (the cause of Kaposi's sarcoma) and herpes zoster (the virus responsible for shingles and chicken pox). They differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which is derived from a Greek word meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive state for some indeterminate time.

There are two forms of the herpes simplex virus:

Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)

These viruses are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule has been to assume that HSV-1 infections occur in the oral cavity (mouth) and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted. It is now widely accepted, however, that either type can be found in either area and at other sites. In fact, HSV-1 is now responsible for up to half of all new cases of genital herpes.

For infection to occur, the following conditions must apply:

The herpes simplex virus passes moves through bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores.
The virus must have direct access to the noninfected person through injuries in their skin or mucus surfaces (such as in the mouth or genital area).

When herpes simplex virus enters the body, the infection process typically takes place as follows:

The virus enters vulnerable cells in the lower layers of skin tissue and tries to reproduce in the cell nuclei. Scientists are close to decoding the genetic structure of herpes simples virus and to discovering how the virus works its way into specific cells. The virus may have specially shaped proteins called cell adhesion molecules that can allow the virus to enter healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of the virus and help the infection move from cell to cell.
Even after it has entered the cells, the virus never causes symptoms in most cases.
However, if the virus destroys the host cells when it multiplies, inflammation and fluid-filled blisters or ulcers appear. Once the fluid is absorbed, scabs form, and the blisters disappear without scarring.
After the first time they multiply, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends (the dorsal root ganglia).
Here, the virus lives in an inactive (latent) form. The virus does not multiply, but both the host cells and the virus survive.
At unpredictable times, the virus begins multiplying again. It then goes through a period called shedding. During those times, the virus can be passed into bodily fluids and infect other people. Unfortunately, a third to half of the times shedding occurs without any symptoms at all.
Eventually, the symptoms return in most cases, causing a new outbreak of blisters and sores.

This close-up view of early herpes outbreak shows small, grouped blisters (vesicles) and lots of inflammation (erythema).

Symptoms

Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new herpes simplex virus 2 (HSV-2) infections and about a third of new herpes simplex virus 1 (HSV-1) infections do not produce symptoms.

Skin Eruptions and Pain. Skin eruptions will appear 2 - 12 days after the initial exposure to the virus.

The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters -- the characteristic herpes virus lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
When the crust falls off, the lesions are no longer contagious. (Rarely, the virus may still be active in nearby tissue.)
Once the virus gains entry to a site in the body, it can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in the first (primary) virus attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome).

Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually go away within a week.
Lymph glands near the site may be swollen as well.

It may be especially important to identify a first (primary) infection -- if possible -- and to treat it as soon as possible. Some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that time, the virus does not produce symptoms and cannot be transmitted to other people.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus multiples and can be transmitted through fluids and infect other people. This occurs during an outbreak. However, in a third to half of cases shedding occurs without any symptoms at all (asymptomatic). One study reported that about 40% of all people infected with herpes simplex virus (HSV) had sheeding of the virus without symptoms more than 5% of the time. (Other evidence suggests shedding occurs much more often -- 9 - 28% of the time.) About half of shedding episodes without symptoms happen within a few days before or after an outbreak and can last about 1.5 days. Asymptomatic shedding is much more common with herpes simplex virus 2 (HSV-2) than with herpes simplex virus 1 (HSV-1).

Symptoms of Recurrence. Herpes simplex nearly always recurs. The site on the body and the type of virus influence how often it comes back. The virus usually takes the following course:

Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also have a headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as few as 2 hours or as many as 2 days, steps when the blisters develop. About 25% of the time, recurrence does not go beyond the prodrome stage.
Outbreak. Recurrent outbreaks of herpes simplex virus (HSV) feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they typically heal in 6 - 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but several different factors may be involved. These include sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, and emotional stress. Some studies link recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Oral herpes can be provoked within about 3 days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot kill the virus completely.

Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 1 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by herpes simplex virus 2 (HSV-2), although the rate of simplex virus 1 (HSV-1) genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. While there is no difference in treatment, there can be a difference in disease course. Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area 3 - 14 days after exposure to the virus. If there is a long time between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has already produced antibodies to the virus. These kinds of first infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop symptoms such as flu-like discomfort and fever. The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men:

In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as many as 6 weeks.
Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, people have four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes:

HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some have them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

Patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.


Location and type	Symptoms	Treatments
*Eye (ocular herpetic infection).* Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. The incidence has been highest in children, although it is increasing in older individuals.	Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks. Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers. Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).	Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate-to-severe inflammation. Procedures. Patients with ocular HSV may also need debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. The patient may wear a patch or soft contact lens afterward. Patients with HSV who show scarring in the cornea may need surgery. In rare cases, a corneal transplant may be necessary.
*Brain (HSV encephalitis).* Usually HSV-1, although HSV-2 is typically the cause in newborns. In about 25% of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About a third of cases occur in people under 20 years old, half over age 50, and the balance between ages 20 -50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.
*Finger (herpetic whitlow)*. One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% of cases, and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2 - 3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit. Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir, or foscarnet in patients resistant to acyclovir.
Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
*Other skin areas (herpetic erythema multiforme).* May follow any form of recurrent HSV. Is relatively rare.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.	Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).
Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Click the icon to see an image of herpetic esophagitis.

Transmission

To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through broken skin or a mucous membrane, such as inside the mouth or on the genital area. Each virus can be carried in bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores. The risk for infection is highest with direct contact of blisters or sores during an outbreak.

Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus cannot be transmitted to another person. However, at some point, it often begins to multiply again without causing symptoms (called shedding ). During shedding, the virus can infect other people through exchange of bodily fluids.

Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.

Oral herpes (usually HSV-1) has been detected in both the saliva and blood of patients with active oral infections. It is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. The virus, however, can also enter through the anus, skin, and other areas.

People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests about one-third of all herpes simplex virus 2 (HSV-2) infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.

In the past, genital herpes was mostly caused by HSV-2, but herpes simplex virus 1 (HSV-1) genital infection is increasing, most likely to due to oral sex. Shedding of genital HSV-1 is less common than with HSV-2, but transmission obviously still occurs, as evidenced by the rising prevalence of genital HSV-1. In fact, a person who carries both HSV-1 and HSV-2 poses a greater risk for sexually transmitting HSV-2 than a person who carries only HSV-2. A person who is infected with only HSV-1 has some protection against being infected by HSV-2.

Risk Factors

Everyone is at risk for herpes simplex virus. According to the latest U.S. data from 1999 - 2004, 57.7% of Americans ages 14 – 49 are infected with herpes simplex virus 1 (HSV-1). About 17% of Americans in the same age range test positive for herpes simplex virus 2 (HSV-2). Infection rates for both viruses have declined since the late 1980s. However, infection is lifelong.

Oral herpes is usually caused by HSV-1. The highest incidence of first infection occurs between 6 months and 3 years of age. The incidence in children varies among regions and countries, with the highest rates occurring in crowded and unsanitary regions. Studies suggest that by age 5 more than a third of children in low-income areas are infected compared to 20% of children in middle-income areas. However, by the time children in middle-income areas reach their 30s, about 60% have become infected with HSV-1. After age 40, socioeconomic differences in infection rates become even less pronounced.

The number of Americans with genital herpes increased by 30% from the late 1970s through the early 1990s. However, recent surveys indicate that prevalence is decreasing. A 2006 study in the Journal of the American Medical Association found that among Americans age 14 - 49, the prevalence of herpes simplex virus 2 (HSV-2) decreased by 19% from 1988 - 2004. The decrease was greatest among teenagers age 14 - 19.

The prevalence of herpes virus simplex 1 (HSV-1) also declined, but the percentage of genital herpes infections caused by HSV-1 more than tripled. Among people infected with HSV-1, but not HSV-2, 1.8% were diagnosed with genital herpes from 1999 to 2004 compared with 0.4% from 1988 to 1994. (HSV-2 still causes the majority of genital herpes infections.)

Although the prevalence of genital herpes is declining in the United States, it still remains in epidemic proportions. According to the U.S. Centers for Disease Control and Prevention, at least 45 million Americans age 12 and over have had genital herpes. About 1 in 5 teenagers and adults are infected with genital herpes.

Gender. Anyone who is sexually active is at risk for genital herpes. Studies indicate that around 22% of Americans are infected with HSV-2, with the risk higher in women (26%) than in men (18%). Men, however, have twice as many recurrent infections as women.

Women have an 80 - 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 4 times more likely to be infected than men. In one study of sexually active American teenagers, 15% of the females had evidence of being infected with HSV-2, compared to none of the males. Having a drinking problem greatly increased the likelihood of infection in these young women.

Ethnicity. Although African-Americans are more likely to test positive for HSV-2, Caucasians have a higher risk for active genital symptoms. Over the past few years, the greatest increase in HSV-2 has occurred in Caucasian teenagers.

Compromised Immune Systems. People with compromised immune systems, notably patients with HIV, are at very high risk for HSV-2. Between 68 - 81% of patients with HIV are infected with HSV-2. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and transplant patients.

The following are examples of people who are at particularly risk for specific forms of herpes.

Health care providers, including doctors, nurses, and dentists. This group is at higher than average risk for herpetic whitlow, herpes that occurs in the fingers.
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing. These individuals are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores and usually affects the head or eyes.

Complications

The severity of symptoms depends on where and how the virus enters the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the herpes infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with herpes is also common during pregnancy.

However, although about 1 million pregnancies occur each year in women who have been infected with HSV-2, complications occur in fewer than 4 in 1,000 infected pregnant women.

Approach to the Pregnant Herpes Patient. The approach to a pregnant woman who has been infected by either HSV-1 or HSV-2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study, the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be virus-free, and the newborn must still be tested.)
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at 3 - 5-day intervals prior to delivery to determine whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, a vaginal delivery can be performed and the newborn is examined and cultured after delivery.

Some doctors now recommend anti-viral medication for pregnant women who are infected with HSV-2. Recent studies indicate that acyclovir (Zovirax) or valacyclovir (Valtrex) can help reduce the recurrence of genital herpes and the need for Cesarean sections. Women begin to take the drug on a daily basis beginning in the 36th week of pregnancy (last trimester).

Although 25 - 30% of pregnant women in the U.S. and Europe have a history of herpes simplex virus (HSV-2) infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 - 20,000 births, depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes and a first infection that is acquired early in the pregnancy pose a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are:

During a first infection, the virus is shed for longer periods, and more viral particles are excreted.
An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Infants may acquire congenital herpes from a mother with an active herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not help systemic herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Herpes infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of herpes in the newborn.

Localized infection affects the skin, eyes, and mucous membranes. Herpes simplex virus 1 (HSV-1) usually causes this temporary. However, in some cases, most often herpes simplex virus 2 (HSV-2) infections, later complications develop in 5 - 10% of infants. If untreated, the virus may lead to very severe complications, notably disseminated or central nervous system infection.
Disseminated disease can affect internal organs, such as the liver, lungs, and adrenal glands. It is fatal in up to 80% of newborns if left untreated, and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal, and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications. These may include:

Acute infection in the mother at delivery
Prematurity
Seizures in the infant
Disseminated intravascular coagulopathy, a blood-clotting disorder that can occur in response to infection

Factors that Indicate a Lower Risk for Severe Complications. These may include:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. However, antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first 6 months.

Tests for the Newborn at Risk for Herpes. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 - 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of Herpes in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Doctors and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within 5 - 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
The other half of infected infants develop no lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Doctors should suspect infection in any infant with fever, irritability, lethargy, or poor feeding at 1 week of age.

Treatment of Herpes in the Newborn. If doctors suspect herpes virus infection in a newborn, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 - 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term acyclovir by mouth to newborns following the initial infection will improve the outcome.

Herpes Encephalitis. Each year in the U.S., herpes accounts for 2,100 cases of encephalitis, a rare but extremely serious brain disease. Herpes simplex virus 1 (HSV-1) is usually the cause, except in newborns. In about 70% of cases of infant herpes encephalitis, the disease occurs when a latent herpes simplex virus 2 (HSV-2) is activated. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have both significantly improved survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from herpes encephalitis depends on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within 2 days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk than men for herpes meningitis. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for up to a week, although recurrences have been reported.

Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein that is critical in the development of Alzheimer's disease.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that go away in a few days.

Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of cases of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture, resulting in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks.Rarely, it can lead to a viral infection. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of patients with herpes, 82% felt depressed, and 75% were worried about rejection. Over 25% had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes simplex is particularly devastating when it occurs in immunocompromised patients and, unfortunately, coinfection is common. People infected with herpes have a three-fold increased risk for contracting HIV. Furthermore, studies have reported that 68 - 81% of patients with HIV are also infected with herpes simplex virus 2 (HSV-2).

Patients with HIV are particularly vulnerable to complications. When a person has both viruses, there appears to be a synergy between them, with each virus increasing the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be transmitted to sexual partners. In addition, episodes of herpes recurrence increase, at least temporarily, HIV viral load. An important 2007 study in the New England Journal of Medicine indicated that treatment of HSV-2 with valacyclovir can help reduce plasma and genital levels of HIV in women who are infected with both viruses. Researchers are continuing to investigate whether treatment of HSV-2 may help reduce the risk of HIV transmission.

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including:

Pneumonia
Inflammation of the esophagus
Encephalitis (inflammation of the brain)
Destruction of the adrenal glands
Disseminated herpes (spread of infection throughout the body)
Liver damage, including hepatitis

Hepatitis caused by primary or recurrent herpes can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications, or even a liver transplant, when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Several conditions have been linked to herpes infections, although the association has not been substantiated in most cases.

Arthritis, usually in a single joint, has been sporadically reported as a result of herpes infection.
People with herpes simplex virus 2 (HSV-2) may be more likely to get sexually transmitted hepatitis C.
Some evidence suggests that herpes simplex virus 1 (HSV-1) may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
Some studies have reported associations between herpes simplex and heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Diagnosis

The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, some patients who carry the virus may not have visible genital lesions. Laboratory tests are essential for confirming herpes diagnosis. These tests include virologic tests (which examine samples of skin taken from the lesion) and serologic tests (blood tests that detect antibodies).

In its 2006 guidelines for sexually transmitted diseases, the U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases.

According to the CDC, up to 50% of first-episode cases of genital herpes are now caused by herpes simplex virus 1 (HSV-1). However, recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than herpes simplex virus 2 (HSV-2). It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations.

Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 3 days of appearance. The viruses, if present, will reproduce in this fluid sample but may take 1 - 10 days to do so. If infection is severe, testing technology can shorten this period to 24 hours, but speeding up the timeframe during this test may make the results even less accurate. Viral cultures are very accurate if lesions are still in the clear blister stage, but they do not work as well for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Polymerase chain reaction (PCR) tests are much more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis (see below). PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures and is not FDA-approved for testing genital specimens. However, because PCR is highly accurate, many labs have used it for herpes testing.

An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and microscopically examined for the virus. Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies) indicate herpes infection. The test is quick but accurate 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.

Serologic (blood) tests can identify antibodies that are specific to the virus and its type, herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.

Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:

Glycoprotein gG-1 is associated with HSV-1
Glycoprotein gG-2 is associated with HSV-2

Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.

Serologic tests are most accurate when administered 12 - 16 weeks after exposure to the virus. Recommended tests include:

HerpeSelect. This includes two tests: ELISA (enzyme-linked immunosorbent assay) or Immunoblot. They are both highly accurate in detecting both types of herpes simplex virus. Samples need to be sent to a lab, so results take longer than the in-office Biokit test.
Biokit HSV-2 (also marketed as SureVue HSV-2). This test detects HSV-2 only. Its major advantages are that it requires only a finger prick and results are provided in less than 10 minutes. It is very accurate, although slightly less so than the other tests. It is also less expensive.
Western Blot Test. This is the gold standard for researchers with accuracy rates of 99%. It is costly and time consuming, however, and is not as widely available as the other tests.

False-negative (testing negative when herpes infection is actually present) results can occur if tests are done in the early stages of infection. False-positive results (testing positive when herpes infection is not actually present) can also occur, although more rarely than false-negative. Your doctor may recommend that you have the test repeated.

Experts recommend serologic herpes tests especially for:

People who have had recurrent genital symptoms but no negative herpes viral cultures
Confirming infection in people who have visible symptoms of genital herpes
Determining if the partner of someone diagnosed with genital herpes has acquired herpes
People who have multiple sex partners and who need to be tested for different types of STDs

At this time, doctors do not recommend screening for HSV-1 or HSV-2 in the general population.

It make take a number of test to diagnose herpes encephalitis.

Imaging Tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography or magnetic resonance imaging scans may be used to differentiate encephalitis from other conditions.

Brain Biopsy. Brain biopsy is the most reliable method of diagnosing herpes encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain.

Polymerase Chain Reaction (PCR). The polymerase chain reaction (PCR) assay looks for tiny pieces of the DNA of the virus, and then replicates them millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of herpes encephalitis in most cases, eliminating the need for biopsies. The CDC recommends PCR for diagnosing herpes central nervous system infections.

Similar Conditions

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal in 2 weeks without treatment.

Canker sores (Aphthous ulcers) are very common. Typically, they are a shallow ulcer with a white or whitish/yellow base surrounded by a reddish border. This ulcer is seen in an individual with AIDS and is located in front and just below the bottom teeth.

Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly those with impaired immune systems.

Click the icon to see an image of thrush.

Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.

Conditions that may be confused with herpes simplex virus 2 (HSV-2) include bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Simple corneal scratches can cause the same pain as herpetic infection, but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Stevens-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

Click the icon to see an image of the shingles.

Click the icon to see an image of chickenpox.

Home Remedies and Prevention

Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.

Several simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Keep blisters or sores clean and dry with cornstarch or similar product. (Women should not use talcum powder because it may increase their risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Avoid tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain on urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of herpes simplex virus 1 (HSV-1).
Avoid sex during both outbreaks and prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen. Never give children aspirin.

In one study, stress management techniques developed using cognitive-behavioral methods not only were effective in reducing depression in those with hepres simplex virus 2 (HSV-2) but blood test results also revealed lower levels of HSV-2 antibodies, a possible sign of decreased viral activity. In any case, reducing stress using relaxation techniques does no harm.

Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:

Echinacea (Echinacea purpurea )
Siberian ginseng (Eleutherococcus senticosus )
Aloe (Aloe vera )
Bee products that contain propolis, a tree resin collected by bees
Lysine
Zinc

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for herpes simplex:

Echinacea can lower white blood cell levels when taken for long periods of time. This herb can also interfere with drugs that are used to treat immune system disorders.
Siberian ginseng can raise blood pressure levels.
Bee products (like propolis) can cause allergic reactions in people who are allergic to bee stings.
Do not take Lysine with certain types of antibiotics.
'Taking zinc in large amounts (more than 200 mg/day) can cause stomach upset.

Infected people should take several steps to avoid transmitting the virus to others. It is almost impossible to defend against the transmission of oral herpes simplex virus 1 (HSV-1) since it can be transmitted by very casual contact.

Preventing Transmission During an Outbreak. When an outbreak of herpes occurs, the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands and nails after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to 2 hours on cloth and for 4 hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.

Preventing Sexually Transmitted Disease. Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. Condoms are also important during oral sex, as an increasing number of new genital herpes cases are due to HSV-1, particularly among younger people.

The use of condoms for preventing the transmission of herpes simplex virus 2 (HSV-2) is not foolproof. Even a small tear can permit passage of the virus. However, studies show that regular condom use can significantly reduce the risk of HSV-2 infection.

Condoms made of latex are less likely to slip or break than those made of polyurethane. “Natural” condoms made from animal skin do not protect against HSV infection because herpes viruses can pass through them.

Women appear to be better protected than men are by male condoms. The reason may be that men shed HSV-2 from the skin of the penis, which is covered by the condom. However, in women the virus is often shed from skin areas around the genital area, which can have contact to skin areas in the male outside the condom.

The female condom is another option for infected women or partners of infected men. The female condom covers a large area and is an effective barrier to sexually transmitted viruses.

Note on Lubricants and Spermicides. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used. Oil-based lubricants (petroleum jelly, body lotions, cooking oil) can weaken latex.

Some condoms come prelubricated with sperm-killing substances called spermicides, which are no longer recommended. The standard active ingredient in spermicides is nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9 does not provide any additional protection against sexually transmitted diseases (STDs). It can cause yeast and urinary tract infections in women. In addition, it can cause irritation around the genital areas, which makes it easier for herpes and other STDs to be transmitted. In fact, research indicates that it actually increases the risk for HIV in women.

Treatment for Genital Herpes

No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped, and, even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce symptoms and improve healing times.

Antiviral drugs called nucleosides or nucleotide analogues are the main drugs used to treat genital herpes. They are taken by mouth. (Acyclovir is also available as an ointment, but the oral form is much more effective.) These drugs limit herpes viral replication and its spread to other cells. They are not cures, however.

Three drugs are approved to treat genital herpes:

Acyclovir (Zovirax or generic)
Valacyclovir (Valtrex)
Famiciclovir (Famvir)

When a patient has herpes for the first time, the drug is taken several times a day for 7 -10 days. Then the drugs are used either to suppress the virus or to treat outbreaks.

To treat outbreaks, regimens depend on the medication and dosage prescribed:

Acyclovir: 400 mg three times a day for 2 days or 800 mg twice a day for 5 days
Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days
Famiciclovir: 125 mg twice a day for 5 days or 1000 mg twice a day for 1 day. (In 2006, famiclovir was approved as the first one-day treatment for recurrent genital herpes.)

To suppress outbreaks, treatment requires taking pills daily on a long-term basis. (Acyclovir and famiciclovir are taken twice a day, valacyclovir once a day.) Suppressive treatment can reduce outbreaks by 70 – 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Valacyclovir may work especially well for preventing herpes transmission among heterosexual patients when one partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, valacyclovir may not be as effective as acyclovir or famiciclovir for patients who have very frequent recurrences of herpes (more than 10 outbreaks per year).

Because the frequency of herpes recurrences often diminishes over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it. Studies suggest that daily drug therapy is safe and effective for up to 6 years with acyclovir, and up to 1 year with valacyclovir or famciclovir.

Side Effects. Nausea and headache are the most common side effects, but in general these drugs are safe. Although there is some evidence these drugs may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these medications.

Risk for Resistant Viruses. As with antibiotics, doctors are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They feel that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. However, patients who do not respond to standard regimens should be monitored for emergence of drug resistance.

Some doctors believe that developing an effective herpes vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold the potential for eliminating latent, lifelong infections.

In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) launched the Herpevac Trial for Women. The NIAID seeks to enroll 7,500 women between the ages of 18 and 30 who test negative for both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infection. The trial is being conducted at more than 40 sites in the United States and Canada. Participants are randomly assigned to receive either three doses of the experimental herpes vaccine or an investigational hepatitis A vaccine. The women will be observed for 20 months following the initial vaccination to determine if they contract genital herpes (or, for the control group, hepatitis A) during this time. The vaccine used in the trial does not contain live virus and will not itself cause infection.

The premise for the Herpevac trial is based on results from two studies published in the New England Journal of Medicine in 2002. In these studies, a glycoprotein D vaccine was effective in preventing genital herpes in women who were not infected with HSV-1 or HSV-2. For uninfected women, the risk of contracting genital herpes was reduced by nearly 75 percent. The vaccine was not useful, however, for women already infected with HSV-1 and was ineffective in men regardless of their virus status.

Treatment for Oral Herpes

Acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) -- the anti-viral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes. In addition, acyclovir is available in topical form, as is penciclovir (a related drug).

These ointments or creams help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.

Penciclovir (Denavir) heals herpes simplex virus 1 (HSV-1) sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of pain. Ideally, the patient should apply the cream within the first hour of symptoms, although benefits have also been noted with later application. It is continued for 4 consecutive days, and should be reapplied every 2 hours while awake.
Acyclovir cream (Zovirax) works best when applied early on (at the first sign of pain or tingling).
Docosanol cream (Abreva) is the only FDA-approved non-prescription ointment for oral herpes. The patient applies the cream five times a day, beginning at the first sign of tingling or pain. Studies have been mixed on the cream’s benefits.
Over-the-counter topical anesthetics may provide modest relief. They include Anbesol gel, Blistex lip ointment, Campho-phenique, Herpecin-L, Viractin, and Zilactin.

Resources

www.ashastd.org -- American Social Health Association
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/std/herpes -- Centers for Disease Control and Prevention
www.herpesdiagnosis.com -- Herpes Diagnosis
www.herpesalliance.org -- International Herpes Alliance
www.gotherpes.com -- Herpes support site
www.niaid.nih.gov/dmid/stds/herpevac -- Herpevac (herpes vaccine) clinical trial information

References

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume JC, Lechat P, Chosidow O. A meta-analysis to assess the efficacy of oral antiviral treatment to preventgenital herpes outbreaks. J Am Acad Dermatol. 2007 Aug;57(2):238-46. Epub 2007 Apr 9.

Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(:790-9.

Review Date:
9/9/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Bipolar disorder

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Risk Factors
Causes
Prognosis
Diagnosis
Treatment
Medications
Other Treatments
Therapy and Lifestyle Chang...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17. Risperidone (an atypical antipsychotic) and lithium (a mood stabilizer) are the two drugs currently approved for treating pediatric patients with bipolar disorder.

Drug Warnings

Olanzapine (Zyprexa, Symbex) causes a greater risk for high blood sugar than other atypical antipsychotics, according to updated information added to the drug’s warning label. Olanzapine also causes weight gain and can increase the risk for unhealthy cholesterol levels.
All atypical antipsychotics increase the risk for diabetes. Patients who take these drugs should receive regular screenings for changes in blood sugar levels. Patients should also have their cholesterol levels monitored.

Bipolar Disorder in Children and Adolescents

Diagnoses of bipolar disorder in children have increased 40-fold in the past decade, according to an analysis in the Archives of General Psychiatry. There is debate whether bipolar disorder in children was under-diagnosed in the past or is being over-diagnosed now.
Bipolar symptoms in children differ from those of adults, with some symptoms overlapping with behavioral and conduct disorders. New guidelines from the American Academy of Child and Adolescent Psychiatry (AACP) caution that a diagnosis of bipolar disorder must be carefully made, especially considering the risks associated with drug therapy. The AACP also advises that there are currently no established criteria for diagnosing bipolar disorder in preschoolers.

Bipolar Depression

The antidepressants bupropion (Wellbutin) and paroxetine (Paxil) do not increase the risk for mania, but neither do they help ease depression any more than mood stabilizers, suggests a 2007 study in the New England Journal of Medicine.
Intensive psychotherapy in combination with medication can help improve depression outcomes, indicates a 2007 study in the Archives of General Psychiatry.

Introduction

Bipolar disorder, or manic-depressive illness, is characterized by moods that swing between two opposite poles:

Periods of mania with exaggerated euphoria, irritability, or both
Episodes of depression

Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental, and other factors.

Bipolar disorder is classified according to the pattern and severity of the symptoms as bipolar disorder I, bipolar disorder II, or cyclothymic disorder. Patients with one type may develop another. Nevertheless, they are distinct enough to merit separate classifications, and some experts believe these conditions are actually separate disorders with different biologic factors that account for their differences.

Bipolar Disorder I. Bipolar disorder I is characterized by at least one manic episode, with or without major depression, that lasts for at least 7 days. In 60 - 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories.

Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week, and it can last for months. Typically, depressive episodes tend to last 6 - 12 months, if left untreated.

Bipolar Disorder II and Hypomania. Bipolar disorder II is characterized by episodes of predominantly depressive symptoms, with occasional episodes of hypomania, which last for at least 4 days. Hypomania is similar to mania, but the symptoms (typically euphoria) are less severe and do not last as long.

Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.

Cyclothymic Disorder. While cyclothymic disorder is not as severe as either bipolar disorder II or I, the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. (One report, in fact, referred to these patients as having "darker" natures, while bipolar II patients were "sunnier.")

The disorder lasts at least 2 years, with single episodes persisting for more than 2 months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.

Symptoms of the Depression Phase. The symptoms of depression experienced in bipolar disorder are almost identical to those of major depression, the primary form of unipolar depressive disorder. They include:

Sad mood
Fatigue or loss of energy
Sleep problems such as insomnia, excessive sleeping, or shallow sleep with frequent awakenings
Appetite changes
Diminished ability to concentrate or to make decisions
Agitation or markedly sedentary behavior
Feelings of guilt, pessimism, helplessness, or low self-esteem
Loss of interest or pleasure in life
Thoughts of, or attempts at, suicide

Distinguishing Between Unipolar and Bipolar Depression. It is often difficult to differentiate between unipolar and bipolar depression, particularly in patients with bipolar II disorder. They may differ in the following ways:

Bipolar depression typically lasts 2 - 3 months -- not as long as in major depression (although left untreated some bipolar disorder episodes can last 6 - 12 months or longer).
People with unipolar depression can still experience a variety of other moods, but none meet the criteria for a manic state.
Depressive symptoms in those with bipolar disorder tend to vary. For example, some patients experience increased sleep, gain weight, and feel a heaviness and slowness in their bodies. Other patients with bipolar depression experience impaired sleep, but unlike patients with unipolar depression, they do not feel sleepy the next day.
Bipolar depressive episodes tend to develop more gradually than do those caused by major depression.

Symptoms of the Acute Manic Phase. The acute pure manic phase is always characterized by mood elevation, presented in the following ways:

Exaggerated euphoria (a feeling of great happiness or well-being)
Irritability
Both euphoria and irritability

The episode lasts for at least few days but, in some cases, the episode may last weeks or even months and may be severe enough to require hospitalization.

Other symptoms must also be present to make a diagnosis. Some mental health professionals use the mnemonic device DIGFAST to identify them. In general, for a diagnosis of mania, a patient must have experienced either euphoria with three DIGFAST symptoms or irritability with four of these symptoms:

D. Distractibility. This is the most common symptom, and it is usually characterized by the inability to pay attention to any activity for very long.
I. Insomnia in mania typically means having high energy and requiring less sleep. (This differs from insomnia in depression, in which the patient has low energy plus an inability to sleep.)
G. Grandiosity. Patients with this symptom have an inflated sense of themselves, which, in severe cases, can be delusional. Close to 60% of all manic patients experience feelings of being all-powerful. Sometimes they feel that they are godlike or have celebrity status.
F. Flight of ideas. Thoughts literally race.
A. Activity. The patient may show an increase in intensity in goal-directed activities, which are related to social behavior, sexual activity, work or school.
S. Speech. The patient may talk excessively.
T. Thoughtlessness. Excessive involvement in high-risk activities is present (such as unrestrained shopping, promiscuity). Mood disturbance may be severe enough to damage one's job or social functioning or one's relationships with others. Some patients require hospitalization to prevent harm to others or to themselves.

Some patients with bipolar I may experience psychotic symptoms, including thought disorders, hallucinations, and catatonia (a state in which the patient goes into a stupor for long periods, which may give way to short periods of extreme excitement).

Hypomania. With hypomania the symptoms of mania are milder and of shorter duration (but they last at least 4 days). They do not affect social or work life as dramatically.

Mixed Mania State Symptoms. Mixed mania (also called mixed episodes or dysphoric mania) are manic episodes that also have a depressive component. In such a state, mania is present to a significant degree, but depression is present most of the day and nearly every day. Such mixed symptoms occur for at least a week.

Depressive Mixed State Symptoms. Depressive mixed state is characterized by major depression as the primary emotional state with manic features (such as irritability, distractibility, and racing thoughts). Such patients may receive an inaccurate diagnosis of unipolar depression.

Risk Factors

Between 1 - 2 million Americans may suffer from bipolar disorder. Researchers estimate that about 1% of Americans experience bipolar disorder during the course of their lifetime, but some studies indicate that prevalence may be as high as 4%. There is differing opinion on how to diagnose and categorize bipolar symptoms, which affects these estimates. The majority of people with bipolar disorder also have other psychiatric disorders, particularly anxiety and substance abuse.

Bipolar disorder affects both sexes equally, but there is a higher incidence of rapid cycling, mixed states, and cyclothymia in women. Early-onset bipolar disorder tends to occur more frequently in men and it is associated with a more severe condition. Men with bipolar disorder also tend to have higher rates of substance abuse (drugs, alcohol) than women.

Bipolar disorder frequently occurs within families, although genetic factors account for only about 60% of cases. Family members of patients with bipolar disorder also have a higher than average incidence of other psychiatric problems. They include schizophrenia, schizoaffective disorder, anxiety disorders, ADHD, and major depression.

Causes

No single cause may ever be found for bipolar disorder. Instead, a combination of biologic, genetic, and environmental factors appears to trigger and perpetuate the chemical imbalances in the brain that shape this complex disorder. Biologic factors observed or considered in bipolar disorder, as detected by use of imaging scans and other tests, include:

Oversecretion of cortisol, a stress hormone
Excessive influx of calcium into brain cells
Abnormal hyperactivity in parts of the brain associated with emotion and movement coordination
Low activity in parts of the brain associated with concentration, attention, inhibition, and judgment
A superfast "biologic clock"

The so-called biologic clock is a tiny cluster of nerves called the supra chiasmatic nucleus, or SCN. The SCN is located in the center of the brain in the hypothalamus region. It regulates a person's circadian rhythm, the daily cycle of life, which influences sleeping and waking.

The genetics of bipolar disorder are the most intensively studied of all psychiatric diseases. Multiple genes, involving several chromosomes, have been linked to its development. Bipolar disorder also may share these genetic factors with other disorders, including schizophrenia, epilepsy, and panic disorder. It is not clear if some of these disorders are variations of a single disease or separate disorders.

Bipolar Disorder and Schizophrenia. Researchers have been investigating whether common biologic factors are involved with schizophrenia, severe bipolar disorder, and other psychoses. Schizophrenia and bipolar disorder often show up in the same family. Researchers are identifying a number of common genetic and biologic pathways that they both share. Bipolar Disorder and Epilepsy. Neurotransmitters called gamma aminobutyric acid (GABA) and norepinephrine have been implicated in mania:

GABA helps prevent nerve cells from over-firing
Norepinephrine is a hormone that involves stress

Some research has associated similar biologic mechanisms in patients with epilepsy and bipolar disorder. As in epilepsy, the more episodes a bipolar disorder patient experiences early in the course of the disease, the more frequent and severe later episodes will be. Antiseizure drugs, in fact, can play an important role in the treatment of bipolar disorder.

Panic Disorder and Bipolar Disorder. Researchers are also studying the common biologic and genetic factors between panic disorder and bipolar disorder. While specific genes have not yet been identified, some researchers studying these illnesses now believe that they may represent different forms of a shared, complex condition.

Prognosis

Bipolar disorder can be severe and long-term, or it can be mild with infrequent episodes. Patients with the disease may experience symptoms in very different ways. A typical bipolar disorder patient averages 8 - 10 manic or depressive episodes over a lifetime. However, some people experience more and some fewer episodes.

Typical Bipolar Cycles. In most cases of bipolar disorder, the depressive phases far outnumber manic phases, and the cycles of mania and depression are neither regular nor predictable. Many patients experience mixed mania, or a mixed state, in which both mania and depression coexist for at least 7 days.

Rapid Cycling. About 15% of patients with the disorder have a temporary, complicated phase known as rapid cycling. With this phase the manic and depressive episodes alternate at least four times a year and, in severe cases, can even progress to several cycles a day. Rapid cycling tends to occur more often in women and in those with bipolar II. Typically, rapid cycling starts in the depressive phase, and frequent and severe episodes of depression may be the hallmark of this event. This phase is difficult to treat, particularly since antidepressants can trigger the switch to mania and set up a cyclical pattern.

Differences Between Children and Adults. Research suggests that symptoms of bipolar disorder in children and adolescents differ from those of adults. While adults with bipolar disorder usually have distinct and persistent periods of mania and depression, children with bipolar disorder fluctuate rapidly in their mood and behavior. Mania in children is characterized by irritability and belligerence whereas adults tend to experience euphoria. Children with bipolar depression are frequently angry and restless, and may have additional mood and behavioral disorders such as anxiety, attention deficit hyperactivity disorder, conduct disorder, and substance abuse problems.

Medical evidence has shown that patients with bipolar disorder have higher death rates from suicide, heart problems, and death from all causes than those in the general population. Patients who get treatment, however, experience great improvement in survival rates, including deaths from suicide and heart disease.

Bipolar disorder usually first occurs between the ages of 15 - 30 years, with an average age of onset at 25 years. However, bipolar disorder can affect people of all ages, including children. Bipolar disorder that occurs late in life often accompanies medical and neurological problems (particularly cerebrovascular disease, such as stroke). It is less likely to be associated with a family history of the disorder than earlier-onset bipolar disorder.

Patients with bipolar disorder, especially type II or cyclothymic disorder, have frequent episodes of major depression. Anxiety disorders also commonly coexist in these patients. For example, the occurrence of panic disorder in patients with bipolar disorder is 26 times that of the general population. Patients with bipolar disorder, particularly those with type II, are also subject to phobias. In one study, the presence of anxiety disorders was also associated with longer and more severe bipolar depressive episodes and with a higher risk for suicide.

Symptoms of bipolar disorder in children are often confused with attention-deficit hyperactivity disorder (ADHD). Furthermore, the two conditions can coincide. In one study, 65% of adolescents with bipolar disorder met criteria for ADHD. The risk for both diagnoses is highest in white males. Symptoms are also more severe in people with both conditions. Some researchers believe that many of these disorders may actually be variations of a single disease.

The risk for suicide is very high in patients who suffer from bipolar disorder and who do not receive medical attention. Between 10 - 15% of patients with bipolar disorder I commit suicide, with the risks being highest during episodes of depression or mixed mania (simultaneous depression and mania). Some studies suggest that the risk for suicide in patients with bipolar disorder II is even higher than it is for those with bipolar disorder I or major depressive disorder. Patients who also suffer from an anxiety disorder are also at greater risk for suicide. (Rapid cycling, although a more severe variation of bipolar disorder, does not appear to increase the suicide risk in patients with bipolar disorder.)

Many pre- and early adolescent children with bipolar disorder are more severely ill than are adults with the disease, and the risk for suicide is high. They have a higher risk for mixed mania, multiple and frequent cycles, and a long duration of illness without well periods.

Studies suggest that patients with bipolar disorder may have varying degrees of problems with short- and long-term memory, speed of information processing, and mental flexibility. Such problems persist even between episodes. They tend to be more severe when a person has more manic episodes. Medications used for bipolar disorder could be responsible for some of these abnormalities, although some evidence suggests that such traits may have a biologic basis. These mental difficulties may make it harder for these patients to comply with medications or to participate in complex psychotherapies.

A small percentage of bipolar disorder patients demonstrate heightened productivity or creativity during manic phases. More often, however, the distorted thinking and impaired judgment that are characteristic of manic episodes can lead to dangerous behavior, including:

Spending money with reckless abandon, causing financial ruin in some cases
Angry, paranoid, and even violent behaviors
Openly promiscuous behavior

Such behaviors are often followed by low self-esteem and guilt, which are experienced during the depressed phases. During all stages of the illness, patients need to be reminded that the mood disturbance will pass and that its severity can be diminished by treatment.

Cigarette smoking is prevalent among patients with bipolar disorder, particularly those who have frequent or severe psychotic symptoms. Some experts speculate that, as in schizophrenia, nicotine use may be a form of self-medication because of its specific effects on the brain.

Up to 60% of patients with bipolar disorder abuse other substances (most commonly alcohol, followed by marijuana or cocaine) at some point in the course of their illness.

The following are risk factors for alcoholism and substance abuse in patients with bipolar disorder:

Having mixed-state episodes rather than ones of pure mania
Being a man with bipolar disorder

Patients do not manifest their negative behaviors (such as spending sprees or even becoming verbally or physically aggressive) in a vacuum. They have a direct effect on others around them. It is very difficult for even the most loving of families or caregivers to be objective and consistently sympathetic with an individual who periodically and unexpectedly creates chaos around them.

Many patients and their families find it difficult to accept that these episodes are part of an illness and not simply extreme, but normal, characteristics. Such denial is often strengthened by patients who are highly articulate and deliberate, and who can intelligently justify their destructive behavior, not only to others, but also to themselves.

Family members may also feel socially alienated by the fact of having a relative with mental illness, and feel forced to conceal this information from acquaintances.

The economic burden of bipolar disorder is significant. It is estimated that the disorder costs the U.S. workplace about $14.1 billion annually in lost productivity, mostly due to poor functioning on the job. According to a 2006 study sponsored by the U.S. National Institute of Mental Health, bipolar disorder accounts for twice as much lost productivity as major depressive disorder (MDD), despite the fact that MDD is more prevalent. Each worker with bipolar disorder loses about 66 workdays a year compared with 27 workdays a year for workers with MDD. Research suggests that bipolar disorder’s depressive episodes impair productivity more than its manic episodes.

People with mental illness have a higher incidence of many medical conditions, including heart disease, asthma and other lung problems, gastrointestinal disorders, skin infections, diabetes, hypertension, migraine headaches, hypothyroidism, and cancer. Patients with bipolar disorder are also less likely to receive medical care than people without mental disorders. Substance abuse, including smoking, alcoholism, and drug abuse, also contributes to many of these problems as well as reduced access to care. Medications used for bipolar disorder can also increase the risk for medical problems.

However, people with bipolar disorder and other mental illness have a higher risk for a number of these conditions independent of these factors.

Diabetes. Diabetes is diagnosed almost three times more often in people with bipolar disorder than it is in the general population. Many patients with bipolar disorder are overweight, with about 25% meeting the criteria for obesity. Being overweight is a significant risk factor for diabetes and so it may be the common factor in both diseases. Drugs used to treat bipolar can also cause weight gain and diabetes. Common genetic factors in diabetes and bipolar disorder may cause a rare disorder called Wolfram syndrome and other problems with carbohydrate metabolism.

High Blood Pressure. Patients with bipolar disorder may be at a higher risk for high blood pressure (hypertension) than patients without the disorder. The high prevalence of hypertension among patients with bipolar disorder may also account for their greater risk for illness and death from heart-related conditions.

Migraine Headaches. Migraines are common in patients with a number of mental illnesses, but they are particularly common among patients with bipolar II disorder. Patients with bipolar II suffer from migraine more frequently than patients with bipolar I, suggesting that different biologic factors may be involved with each bipolar form.

Hypothyroidism. Hypothyroidism (low thyroid levels) is a common side effect of lithium, the standard treatment for bipolar. However, evidence also suggests that patients, particularly women, may be at higher risk for low thyroid levels regardless of which medications they use. Hypothyroidism may, in fact, be a risk factor for bipolar disorder in some patients.

Diagnosis

Bipolar disorder is more common than previously thought, but this illness, particularly bipolar disorder II, is still poorly recognized in the family-practice setting. It is estimated that only a third of affected people are accurately diagnosed.

When making a diagnosis of bipolar disorder, it is important that the doctor rule out other conditions that may be causing symptoms of bipolar disorder.

Distinguishing Mania from Normal Euphoria or Joy. A major difficulty with a diagnosis of bipolar disorder is the tendency for a patient to be unable to recognize his or her own condition, particularly when in the manic state. The patient often denies their symptoms, which may be perceived as positive feelings. The doctor should take a careful and complete history of any and all episodes of depression, mania, or both. Hypomania, the less severe variant of mania, may be particularly difficult to distinguish from normal joy or euphoria. It can often be distinguished by the following characteristics:

Hypomania persists for at least 4 days
Patients with hypomania are easily distracted and overly talkative
Patients with hypomania have difficulty functioning

Distinguishing Unipolar from Bipolar Depression. People with bipolar disorder are more likely to seek help because of a depressive episode and may not have a manic episode until they have experienced three or more depressive episodes. In such cases, the condition is often diagnosed as major depression. An accurate diagnosis is important because patients with bipolar disorder who are inappropriately medicated solely with antidepressants have a higher incidence of rehospitalization than do other bipolar disorder patients.

Bipolar disorder should be suspected in patients who have been treated for depression and who had a fast and good response, followed by the return of depression and failure to respond to other antidepressant treatment.

A family history of manic-depressive illness may make a doctor suspicious, but a diagnosis of bipolar disorder cannot be established until a manic or hypomanic episode has occurred. Patients with bipolar II disorder and those with depressive mixed state are most likely to be misdiagnosed with depression.

Attention Deficit Hyperactive Disorder (ADHD). Children or adolescents with bipolar disorder may be inappropriately diagnosed with attention-deficit hyperactivity disorder. ADHD and bipolar disorder often cause inattention and distractibility, and the two disorders may be difficult to distinguish, particularly in children. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary distinction between bipolar disorder and ADHD is the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not those with ADHD.

Schizophrenia. Severe manic episodes that include delusions and hallucinations may be easily confused with schizophrenia. (African-American men are more likely to be diagnosed with schizophrenia than with bipolar disorder.) The key factors that distinguish bipolar disorder from schizophrenia include:

The presence of one or more manic or hypomanic episodes in bipolar disorder, but not in schizophrenia
A flat emotional expression, with no variability in the voice among people with schizophrenia
People with bipolar disorder are typically very expressive

Substance Abuse. Up to 60% of patients with bipolar disorder abuse alcohol and drugs at some point during their illness. Both diagnosis and treatment are difficult in such cases, since substance abuse is often a method of self-treatment, and withdrawal can produce symptoms of mania or severe depression. The effects of cocaine in a heavy user can also produce abnormal mood swings that closely resemble those of bipolar disorder.

Other Causes of Mood Swings. Other conditions that can cause mood swings include:

Thyroid disorders
Adrenal disorders (Addison's disease or Cushing syndrome)
Vitamin B12 deficiency
Neurologic disorders such as Huntington's disease, epilepsy, brain tumors, encephalitis, or multiple sclerosis
Medications, including corticosteroids and certain drugs used to treat anxiety and Parkinson's disease

Patients should be tested for drugs or alcohol if the doctor suspects that they have been using these substances. Blood tests for thyroid function should also be performed.

Noninvasive imaging tests of the brain using magnetic resonance imaging (MRI) and positron-emission tomographic (PET) scans are being evaluated in clinical trials for detecting abnormalities in the brain. The results of these tests may eventually help identify bipolar disorder and test the effectiveness of various treatments. However, imaging tests do not currently play a role in diagnosing bipolar disorder.

The number of children diagnosed with bipolar disorder has increased dramatically during the past decade. Psychiatrists debate whether bipolar disorder was formerly under-diagnosed in children or whether it is being over-diagnosed now. Part of the controversy concerns the diagnostic criteria used for children and adolescents. Some bipolar symptoms, such as irritable mania, share characteristics with common childhood anger outbursts or behavioral disorders such as conduct disorder and attention deficit hyperactivity disorder. In addition, many children with bipolar disorder also have behavioral and developmental disorders. These overlapping conditions can complicate diagnosis.

The American Academy of Child and Adolescent Psychiatry (AACP) recommends that doctors use specific screening questions to diagnose bipolar disorder. These questions are designed to evaluate periods of mood changes associated with sleep disorders and restlessness. Doctors should also ask about family histories of mood disorders. The AACP cautions that the validity of diagnosing bipolar disorder in children younger than 6 years old has not been established.

Bipolar disorder is treated with powerful psychiatric drugs that can cause serious side effects. It is very important to make sure that a child’s symptoms are due to bipolar disorder, rather than emotional or behavioral issues, before prescribing these medications.

Treatment

Bipolar disorder is a recurrent disease that can be unpredictable. The major goals of treatment are to:

Treat and reduce the severity of acute episodes of mania or depression when they occur
Reduce the frequency of episodes
Avoid cycling from one phase to another
Help the patient function as best as possible between episodes

The doctor will first try to determine what may have triggered the attack and identify any accompanying medical or emotional problems that might interfere with or complicate treatment.

Some experts think that the best way to treat bipolar disorder is through a disease management model, similar to those used for treating diabetes and asthma. In this “collaborative care” model, patients are treated by a multi-disciplinary team of psychiatrists and nurses. The nurses provide patient education on medication side effects, early warning signs of symptoms, and coping skills. In several 2006 studies, patients who received this treatment model reported fewer symptoms, more productive time at work, better relationships with family members, and general improvement in quality of life.

The treatments for bipolar disorder, while very effective, pose some specific challenges for the patient:

Mood variations in bipolar disorder are not predictable, so it is sometimes difficult to tell if a patient is responding to treatment or naturally emerging from a bipolar phase.
A patient with bipolar disorder cannot always reliably inform the doctor about the state of the illness.
The patient is likely to need more than one medication during the course of the disease. This increases the risk for distressing side effects. Noncompliance is common.
Patients often have more than one medical problem and need different drugs to treat each condition. Such medications may interact with drugs used to treat bipolar disorder or increase side effects. For example, children with bipolar disorder have a higher risk for attention deficit-hyperactivity disorder, which is treated with stimulants that can complicate bipolar treatment.
Family members who have not been educated about the disorder may interfere with the treatment.
Treatment strategies for children and the elderly have not been intensively studied and have not been clearly defined.
Treatments may be costly.

The following are the treatment options for most patients with bipolar disorder, depending on the bipolar disorder phase or episode. Patients should understand that, even with aggressive therapy, either mania or depression recurs in almost three-quarters of patients.

Drugs Used in Bipolar Disorder. Mood stabilizing drugs are the mainstay for patients with bipolar disorder. They are defined as drugs that are effective for acute episodes of mania and depression and that can be used for maintenance. The standard first-line mood stabilizers are lithium and valproate. Both drugs stimulate the release of the neurotransmitter glutamate, although they appear to work through different mechanisms. Other drugs may also be used.

Lithium. Lithium has been used for years for bipolar disorder. It remains the best drug for people with pure mania characterized by euphoria and pure depression. Although imperfect, it is also an effective long-term drug for many patients with other bipolar subtypes.
Antiseizure Drugs. Valproate (valproic acid) carbamazepine (Tegretol, Carbatrol, Equetro), oxcarbazepine (Trileptal), and lamotrigine (Lamictal) are the most established antiseizure drugs. Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Clozapine (Clozaril) was the first of these drugs, but it has not yet been approved for treatment of bipolar disorder. The newer atypical antipsychotics include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and ariprazole (Abilify).

Such drugs may be used in combination with each other. Additional drugs, such as conventional antipsychotics, antidepressants, antianxiety drugs, or experimental drugs are used as necessary.

Electroconvulsive Therapy. Electroconvulsive therapy is a very effective treatment that may be administered in certain patients for acute episodes or for maintenance.

Non-Medical Treatments. In addition to medical treatments, psychotherapy and sleep management are also parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), an ongoing trial supported by the National Institute of Mental Health, is the largest treatment study ever conducted for bipolar disorder. With plans to enroll approximately 5,000 patients, STEP-BD aims to evaluate all the best-practice treatment options used for bipolar disorder, including mood-stabilizing medications, antidepressants, and atypical antipsychotics. It will also evaluate psychosocial interventions, including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and psychoeducation. Results of STEP-BD may clarify the best treatments for bipolar disorder.

Step 1. Determine the Need for Hospitalization and Eliminate Triggers. The first step in treating an acute manic episode is to rule out any life-threatening conditions and eliminate any triggers, such as antidepressants or other substances that can elevate moods.

Patients often require hospitalization at the onset of acute mania. The need for hospitalization depends on a number of factors:

Whether the patient is at risk for suicide or for harming others
The availability of social and emotional support at home

Step 2. Control Symptoms of Acute Manic with a Mood Stabilizer. Doctors often try different drugs to control a manic episode. If a current drug does not work well, another type of drug may be added or substituted. It may take several weeks for a mood stabilizer to take effect, and other drugs may be needed.

The following is an example of a stepped approach recommended by some experts:

Initiating a mood-stabilizing drug is the critical first step. Either valproate or lithium is the standard first drug for most manic episodes. Lithium is effective in 60 - 80% of all hypomanic and manic episodes. Carbamazepine is usually used in place of valproate to treat patients with multiple manic episodes, mixed episodes, and rapid cycling. Combinations of these mood stabilizers may be used if the patient does not respond to a single drug.
If the patient does not respond fully within a week, atypical antipsychotics may be added to one or more mood stabilizers. Atypicals include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), apriprazole (Abilify), and ziprasidone (Geodon). Clozapine (Clozaril), the oldest atypical drug, also works well but it is not generally used because of its potential for severe side effects and the need for weekly monitoring of white blood cell counts.

Step 3. Addition of Other Treatments. Other treatments may be added to speed recovery, treat any psychosis, and achieve remission. They include:

Older antipsychotic drugs (also called typical antipsychotics), such as haloperidol (Haldol), may be used for acute mania. They can cause severe side effects, however, particularly extrapyramidal effects, which disrupt motor control. They are not generally used on a long-term basis for treating bipolar disorder.
Benzodiazepines, such as clonazepam (Klonopin) or lorazepam (Ativan), are anti-anxiety drugs that may be particularly beneficial if the patient is experiencing severe mania.
Electroconvulsive therapy. This treatment helps patients who do not respond to medication and may even be life-saving in elderly patients with severe late-onset mania.

Step 4. Terminate Some Drug Treatments. Drugs may be stopped under the following circumstances:

When side effects are intolerable
When the patient does not respond to the maximum dose
When the patient improves and recovery is sustained

In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.

Step 5. Continuation of Mood Stabilizers. Mood stabilizers are typically continued for about 8 weeks, unless the patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.

Depressive episodes pose a particular challenge. They are a significant cause of suffering, yet the use of standard antidepressants poses a significant risk for triggering mania. It is also not clear if standard antidepressants work for bipolar depression. In fact, depressive episodes are very difficult and patients who do not respond to mood stabilizers may endure prolonged depressive episodes up to 2 - 3 months.

Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.

If improvement does not occur within 2 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).

Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to “switch” to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.

An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the Food and Drug Administration (FDA) approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax was the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.

Other Treatments. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches.

The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism, which may have caused this condition. Many patients may require a combination of medications to control rapid cycling:

Antidepressants, particularly SSRIs, may prompt rapid cycling and should be tapered off.
Lithium or valproate is a first-line treatment for rapid cycling.
Lamotrigine is an alternative treatment for rapid cycling.
Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
Electroconvulsive therapy can be useful in emergency situations.

In addition, other measures should be taken:

Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
Patients should avoid exposure to bright light.
All efforts should be made to help the patient sleep normally.

Drugs Used During Maintenance. Relapse occurs in most patients after treatment of acute attacks, and patients who are at high risk for recurring episodes should consider life-long maintenance therapy. This usually involves mood-stabilizing drugs:

Lithium is a first-line mood stabilizer used in maintenance therapy. The anti-epileptic drug valproate is also a first-line treatment. In general, the two work equally well, although valproate may be better for patients who have had multiple manic episodes. There are some differences in side effects, but the drop-out rates between the drugs are similar. Lithium has proved effective for preventing relapses of manic episodes, but may not work as well for controlling depressive symptoms.
Lamotrigine, an anti-epileptic drug, was approved in 2003 for long-term maintenance treatment. It is also used as a first-line drug for treating depressive episodes.
Carbamazepine and oxcarbazepine are other anti-epileptic drugs used as alternative maintenance treatments.
Atypical antipsychotics may be used for maintenance, particularly in combination with a mood stabilizer. In 2004, olanzapine became the first atypical antipsychotic to be approved specifically for maintenance treatment.

The general recommendations for maintenance therapy with lithium are as follows:

The earlier lithium is started in the disease process, the better. Studies suggest that patients on long-term lithium therapy have survival rates comparable to the general population, but those who permanently drop out of therapy have significantly lower survival rates due to an increased suicide risk.
Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.

Information on clinical care of pregnant women with bipolar disorder remains very limited. In fact, in one survey, almost half of women with bipolar disorder were discouraged by their doctors from becoming pregnant. Nevertheless, after careful counseling about medications, possibilities for relapse, and disease severity, nearly two-thirds of them decided to attempt pregnancy.

Risks for Bipolar Episodes. Some studies suggest the following risks for bipolar episodes during and after pregnancy:

In women who discontinue lithium during pregnancy, the chance for recurrence of bipolar disorder is the same as in non-pregnant women, which is over 50%.
Pregnant women with bipolar disorder are at particularly high-risk for recurrence in the period after childbirth. In one study, symptoms recurred in 74% of women after delivery, and another 20% were hospitalized within 90 days after giving birth. The risk for depressive or mixed states is particularly high.

Drugs for Bipolar and Pregnancy. It is not ethical to test drugs during pregnancy, so all known effects of bipolar drugs are reported anecdotally. It is well-known, however, that most mood stabilizers used for bipolar disorder carry a high risk for the fetus, particularly if they are taken during the first trimester. Taking mood stabilizers at the time of delivery may help reduce the risk of manic episodes occurring after the baby is born. However, caution is still advised. Reported effects of drugs taken during pregnancy include:

Lithium can pass through the placenta and affect the fetus. When possible, patients should avoid taking lithium during pregnancy, especially during the first 3 months. Studies report that lithium use during the first trimester may cause heart defects and thyroid problems in the baby. If taken immediately before childbirth, lithium can also cause muscle weakness and drowsiness in newborn infants. Women who must take lithium during pregnancy should take the lowest possible dosage and stop the drug 1 - 2 days before delivery. Mothers who are taking lithium should not nurse their babies, since lithium is concentrated in breast milk.
The antiseizure drugs valproate and carbamazepine both greatly increase the risk for physical malformations, developmental delay, and spina bifida in babies. They appear to have minimal effect on breastfeeding, however. Lamotrigine can cause cleft lip and palate birth defects if taken during the first trimester.
Small studies have suggested that the atypical antipsychotic olanzapine does not increase the risk for birth defects. However, it does pose a great risk for excess weight gain that could be unhealthy during pregnancy. Less is known about the effects of other atypical antipsychotics during pregnancy.

Electroconvulsive Therapy (ECT). In spite of its bad press, ECT appears to be very beneficial for women with bipolar disorder who become pregnant. The patient should discuss this option with her doctor.

Doctors are still trying to decide the best treatment of bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be even more severe in younger people. Parents should consider the potential risks and benefits of treatment for their children.

Until recently, lithium was the only drug approved for treating bipolar disorder in children (age 12 years and older). In 2007, the FDA approved the atypical antipsychotic risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17.

Lithium is generally used as the first-line treatment, with valproate and risperidone (or other atypical antipsychotics) as alternatives. If treatment with a single drug does not work, a combination of drugs may be used.

Lithium and valproate are the drugs most studied in children and adolescents. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination, weight gain (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate). Side effects of risperidone may include drowsiness, fatigue, increased appetite, nausea, dizziness, dry mouth, tremor, and rash.

Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.

Psychotherapy is also an important addition to drug treatment. Therapy that includes the entire family is important. Electroconvulsive therapy (ECT) may benefit adolescents with bipolar I disorder who suffer severe episodes of mania or depression and who have not been helped by medication.

Medications

Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) is one of the standard mood stabilizing drugs for bipolar disorder. Lithium is extremely helpful for most patients and it significantly reduces the rate of hospitalizations in bipolar disorder. Some studies report the following advantages of lithium:

Lithium is effective in 60 - 80% of all hypomanic and manic episodes. (Valproate may be better in patients with multiple manic episodes, mixed episodes, and rapid cycling.)
It helps to prevent relapses.
It helps psychosocial functioning.
It may help reduce the risk for suicide regardless of its effects on stabilizing mood.
It works well for most patients even if they have discontinued taking it and wish to restart treatment.

Administration of Lithium. Lithium may take weeks to become totally effective, so patients should not expect an immediate response during an acute episode. Doctors may take different approaches to administering the drug:

Some doctors initially administer lithium in two low doses and gradually increase the dosage over time until an effective (therapeutic) level is achieved.
Another approach is to administer a higher dose initially and measure blood levels of the drug after 24 hours. The doctor uses this information combined with a chart called a nomogram to calculate the doses most likely to be therapeutic.

In addition to drugs, several factors may affect lithium levels:

Seasonal change -- lithium levels may be higher in summer.
Menstrual cycle -- lithium levels may drop during the premenstrual phase.
Weight loss
Changes in salt intake
Dehydration
Diarrhea

Lithium levels should be monitored regularly. Side effects can occur at therapeutic levels or at those only slightly higher than desired. Blood tests that measure drug levels should be conducted frequently during acute attacks and about every 3 months during maintenance therapy.

Lithium Toxicity. Evidence of moderate toxicity include:

Trembling hands
Nausea
Increased urine output
Blurred vision
Some loss of coordination

Severe reactions occurring at higher blood levels, include:

Vomiting
Convulsions
Uncontrolled jerky movements in arms and legs
Stupor
Coma

Very high blood levels of lithium can be fatal. If overdose occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on the severity:

Patients are given fluids and drugs to increase excretion of lithium salts.
Gastric lavage, a procedure that rinses the stomach, may be used to treat very recent overdoses.
Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.

Side Effects. Even for patients who do not experience a severe response, long-term use of lithium is not without problems. Weight gain is one of the main reasons why some patients want to stop taking the drug. Other side effects include:

An unpleasant taste in the mouth
Hair loss
Skin eruptions that can resemble acne and make psoriasis worse
Low thyroid function
An increased risk for diabetes
A blunted sexual drive
Dulled emotions and lack of mental clarity
Memory loss
Lack of motor coordination
Increased sensitivity to light

In some cases, light sensitivity may slightly affect a person's ability to recognize colors. More seriously, it can cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Thiazide diuretics
ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

Antipsychotics
Anticonvulsants
Calcium-channel blockers

The risks associated with these drug interactions are very low, but caution is needed.

Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.

Noncompliance. Noncompliance is common. One study of lithium users found that patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug.

Side effects are certainly one reason for noncompliance. Some patients regret the loss of their manic episodes and the exhilaration and creativity that sometimes accompany them. In one small study of artists with bipolar disorder, however, only 25% felt their work had declined, while another 25% found no change in their creative output, and 50% believed that lithium had improved their output.

Despite side effects and other concerns, this important drug saves lives. Doctors are confident that lithium, which has been in use for more than 50 years, can be taken safely, even for life, by most patients.

Antiseizure drugs, also called anti-epileptics or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. These drugs may be an alternative for patients (especially substance abusers) who do not tolerate or respond to lithium. They also may be used in combination with lithium, atypical antipsychotics, or other drugs.

Standard Antiseizure Drugs.

Valproate (Depakote), also called valproic acid or divalproex, is now a first option for many bipolar disorder patients. It works well for many patients with mania, rapid-cycling, and mixed states, as well as for patients who are substance abusers. Valproate also helps migraine headaches, a common problem among patients.
Lamotrigine (Lamictal) is approved for maintenance treatment of adults with bipolar I disorder. It appears to be particularly helpful for patients with rapid cycling and bipolar II disorder, in whom depression remains problematic after taking other mood stabilizers.
Carbamazepine (Epitol, Tegretol), a standard alternative antiseizure drug used for mood stabilizing, is usually the second anti-seizure medication of choice. In 2004, the FDA approved an extended release form of carbamazepine (Equetro). Another drug, oxcarbazepine (Trileptal), is similar to carbamazepine.
Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.

General Side Effects. The side effects given here are associated with valproate. Other antiseizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy and then subsiding. Valproate side effects include:

Gastrointestinal problems such as nausea, vomiting, and heartburn
Headaches
Visual disturbances
Ringing in the ear
Hair loss
Weight gain (a significant problem with valproate)
Agitation
Odd movements
Menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
Birth defects when taken by pregnant women
Cognitive impairment and symptoms of Parkinson's disease

Very serious side effects are possible. Stevens-Johnson syndrome (SJS) is a rare but severe and potentially life-threatening, rash that can develop as a side effect of carbamazepine, lamotrigine, oxcarbazepine and other anticonvulsants. Because this is a very serious condition, these drugs are discontinued at the first sign of rash. The risk of serious skin reactions is 10 times higher for patients of Asian ancestry than Caucasians. The FDA recommends that people of Asian ancestry get a genetic test before starting carbamazepine to determine if they are at risk for this side effect.

Other serious side effects, also rare, may include liver damage, convulsions, coma, and pancreatitis.

Atypical antipsychotics are standard drugs for schizophrenia. They are now proving to be beneficial for bipolar disorder when used alone or in combination with the mood stabilizers that treat mania. These drugs include clozapine (Clozaril) (the first atypical antipsychotic), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon).

Olanzapine was the first atypical antipsychotic approved for treatment of bipolar disorder. In 2000, the FDA approved it to treat bipolar mania and mixed states. In 2004, the drug became the first atypical antipsychotic approved for bipolar maintenance treatment.
Symbyax, a drug that combines olanzapine and the antidepressant fluoxetine, was approved in 2003 for treatment of bipolar depression.
Risperidone, ziprasidone, and ariprazole are approved for treatment of bipolar mania and mixed states. Paliperidone (Invega), which is chemically related to risperidone, was approved in 2007 for treatment of schizophrenia but has not yet been approved for bipolar disorder.
Quetiapine is approved for treatment of bipolar mania and bipolar depression, making it the only drug approved for treating both manic and depressive states.
Clozapine has not been approved for treatment of bipolar disorder, but has shown promise in investigational studies. However, this drug has more significant side effects than other atypical antipsychotics. It poses a risk of white blood cell reduction (agranulocytosis).

Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include:

Nasal congestion or runny nose
Drooling
Dizziness
Headache
Drowsiness -- however, these drugs may also cause restlessness and insomnia.
Constipation
Rapid heart beat
Difficulty urinating
Skin rash
Increased body temperature
Confusion, short-term memory problems, disorientation, and impaired attention
Weight gain -- risk is highest with clozapine and olanzapine, lowest with aripiprazole and ziprasidone

More serious risks include:

Diabetes (See Diabetes Risk and Atypical Antipsychotics)
Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest for aripiprazole and ziprasidone.
Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high levels of trigylcerides and total cholesterol.
Seizures
Heat stroke
Sudden drop in blood pressure (hypotension)
A significant drop in white blood cell count (neutropenia) and neutrophils (agranulocytosis) occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored if they take clozapine.
Extrapyramidal side effects, which are lack of motor coordination and involuntary movements
Cataracts and worsening of any existing glaucoma
Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.

Diabetes Risk and Atypical Antipsychotics. In 2003, the FDA requested that the strongest warning be added to the product labels of all atypical antipsychotics. This so-called black box warning advises that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The FDA recommends that:

Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.

Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They may trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.

Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. Another antidepressant, venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.

Side effects of SSRIs include:

Nausea and gastrointestinal problems, which usually wear off over time
Agitation, insomnia, mild tremor, and impulsivity
Dry mouth, which can increase the risk for cavities and mouth sores
Headache
Sexual dysfunction

Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.

Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.

Other Treatments

Electroconvulsive therapy (ECT) is a non-drug treatment for bipolar disease and other mental disorders, such as severe depression. It is commonly called shock therapy. ECT has received bad press since it was introduced in the 1930s. But, over the years it has been refined, and is now considered a very safe treatment.

Research suggests ECT may be particularly beneficial for:

Patients who need immediate stabilization of their condition and who cannot wait for medications to work
Most patients with mania -- especially elderly patients with severe mania
Patients who suffer suicidal thoughts and guilt during the depressive phase
Pregnant patients
Patients who cannot tolerate drug treatments
Patients with certain types of heart problems
Young patients

In a review of studies, about 80% of ECT-treated patients experienced improvement, and for some, it is the only treatment that works.

The Procedure. ECT is performed on an outpatient basis and does not require hospitalization. In general, the ECT procedure is performed as follows:

A muscle relaxant and short-acting anesthetic are given to the patient.
A small amount of electricity is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
The response to ECT is usually very fast, and the patient often needs less medication afterward.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Taking the drug naloxone immediately before ECT may help reduce its effects on concentration and some (but not all) forms of memory impairment. Concerns about permanent memory loss appear to be unfounded.

Biologic Effects of ECT on Bipolar Disorder. The precise way that ECT benefits patients with bipolar disorder is not clear. ECT may help by:

Causing changes in the brain's physiology. For example, ECT may increase the permeability of the blood-brain barrier, produce an antiseizure effect (similar to the effects of antiseizure drugs used as mood stabilizers), and reduce blood flow in parts of the brain associated with improved mood.
Causing various hormonal changes, particularly with thyroid-related hormones.
Balancing dopamine levels. This brain chemical plays an important role in bipolar disorder as well as other conditions for which ECT is sometimes recommended, including delusional depression.
Stimulating growth of neurons in the hippocampus (the area in the brain responsible for memory).

Some studies are finding that maintenance electroconvulsive therapy (ECT) may be helpful for patients who do not respond to medications. In one study of patients with bipolar disorder, those who had intractable recurrent episodes received monthly ECT treatments for more than a year and a half. Without ECT, those patients spent an average of almost half a year in the hospital, suffering at least three episodes annually. After ECT, all the rapid cyclers achieved full or partial remission.

Transcranial Magnetic Stimulation. Repeated transcranial magnetic stimulation (rTMS) is also being studied for unipolar and bipolar depression. Unlike ECT, this procedure does not appear to cause seizures, memory lapses, or impaired thinking. The only common side effect is a mild headache.

Therapy and Lifestyle Changes

Psychotherapy is an important addition to medication. Many approaches are proving to be very useful. Trained mental health professionals can:

Educate patients about bipolar disorder and its treatments
Teach patients to recognize and manage early warning symptoms of imminent manic or depressive episodes
Help them comply with drug regimens
Monitor the patient's on-going status
Intervene early in manic and depressive episodes to reduce the severity of the attack

In addition, psychotherapy can help patients:

Adjust to the reality of the illness and understand the negative consequences of mania -- particularly important for patients who consider their mania to be positive, creative, and exhilarating
Cope with feelings of guilt and remorse that occur after manic episodes
Deal with feelings of imperfection and despair

Therapists trained in cognitive-behavioral therapy (CBT) may be particularly helpful for many patients. CBT is a structured, conscious method that aims to help a patient recognize negative thoughts and behavioral patterns and to change them. CBT is known to be helpful for other mood disorders, including depression and anxiety, and some studies suggest that it benefits bipolar disorder patients as well. For example, in one recent study, patients who were given mood stabilizers and underwent a CBT program that was specifically designed to prevent relapse experienced fewer and shorter episodes and improved social functioning compared to those on mood stabilizers alone.

Using Cognitive-Behavioral Therapy for Bipolar Disorder. Typical goals of CBT for bipolar disorder patients include learning how to:

Recognize manic episodes before they become full-blown and change behaviors during an episode
Cope with depression by developing behaviors and thoughts that may help offset the negative mood

It is very important that partners, family members, or both be involved in therapy. CBT can help them learn how to accept the condition, the need for medications, and how to protect themselves and the patient financially during manic episodes. In fact, one study indicated that when a spouse of a patient learned ways of coping with the illness, the partner's chances of sticking to a prescribed treatment improved.

Supporting the Patient. Recommendations for supporting the patient include:

Create a treatment contract as a first step. In this contract, the patient and family agree to specific steps for maintaining emotional stability. If such measures fail, all parties agree on further actions to be taken during an acute episode, including requests for hospitalization.
Be supportive. Unlike relatives of patients with alcoholism who may be encouraged to get tough, relatives of patients with bipolar disorder must be strongly supportive because of the high risk for suicide with this disorder. Simply listening attentively and being empathic can help.
Get the patient to comply with treatment, even if it means threatening a hospitalization if the patient fails to comply.
Have ready a hotline number or the telephone number of a psychiatrist authorized to commit the patient. The doctor should be willing to facilitate commitment if a patient becomes violent or the family is on the verge of collapse.
Don't feel guilty and don't make the patient feel guilty. Bipolar disorder results from an imbalance of chemicals in the brain and not from anyone's fault.

Support for the Family. Unfortunately, actions that support a bipolar disorder patient may not be intuitive, and they take their toll. Loved ones must also care for themselves or they may also follow a path to severe depression. They should to boost energy and reduce stress through:

Exercise
Meditation
Relaxation techniques
Holidays away from the patient
Involvement in hobbies
Involvement in support groups, Internet resources with chat rooms, and message boards for bipolar disorder caregivers

Interpersonal problems (such as family disputes) and disruptions in daily routines or social rhythms (such as loss of sleep or changes in meal times) may make people with bipolar disorder more susceptible to new episodes of their illness. A form of psychosocial treatment called interpersonal and social rhythm therapy (IPSRT) focuses on maintaining a regular schedule of daily activities to reduce these potential triggers and improve emotional stability. Patients also learn how to avoid problems with personal relationships. Preliminary evidence suggests that IPSRT combined with drug therapy works better than medication alone. A 2-year study of patients with bipolar 1 disorder indicated that IPSRT may help prevent new manic episodes.

Exercise. Exercise is an important part of treatment, particularly in helping manage weight gain. It also helps increase feelings of well-being.

Sleep Management. Good sleep hygiene is particularly important for patients. One study reported that techniques used to enforce healthy sleep helped reduce mood cycling.

Diet. A healthy diet low in saturated foods and rich in whole grains, fresh fruits, and vegetables is important for anyone. People with bipolar disorder should be sure to maintain a regular healthy diet. They may need to restrict calories if they are on medications that increase weight.

Some research indicates that consumption of omega-3 polyunsaturated fatty acids found in oily fish (such as mackerel, sardines, salmon, and bluefish) may help reduce the symptoms of a variety of mental illnesses, including bipolar disorder. Researchers are investigating the effects of eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) supplements for patients who have not responded to other treatments.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.bpkids.org -- Child & Adolescent Bipolar Foundation
www.dbsalliance.org -- Depression and Bipolar Support Alliance
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- The American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry

References

Gentile S. Extrapyramidal adverse events associated with atypical antipsychotic treatment of bipolar disorder. J Clin Psychopharmacol. 2007 Feb;27(1):35-45.

Jarema M. Atypical antipsychotics in the treatment of mood disorders. Curr Opin Psychiatry. 2007 Jan;20(1):23-9.

Mathews M, Muzina DJ. Atypical antipsychotics: new drugs, new challenges. Cleve Clin J Med. 2007 Aug;74(:597-606.

McClellan J, Kowatch R, Findling RL; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2007 Jan;46(1):107-25.

Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007 May;64(5):543-52.

Miklowitz DJ, Otto MW, Frank E, et al. Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program. Arch Gen Psychiatry. 2007 Apr;64(4):419-26.

Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007 Sep;64(9):1032-9.

Morriss RK, Faizal MA, Jones AP, Williamson PR, Bolton C, McCarthy JP. Interventions for helping people recognise early signs of recurrence in bipolar disorder. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004854.

Newcomer JW. Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry. 2007;68 Suppl 1:20-7.

Sachs GS, Nierenberg AA, Calabrese JR, et al. Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med. 2007 Apr 26;356(17):1711-22. Epub 2007 Mar 28.

Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry. 2007 Apr;64(4):442-55.

Smith LA, Cornelius V, Warnock A, Bell A, Young AH. Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disord. 2007 Jun;9(4):394-412.

A.D.A.M. Copyright

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Anorexia nervosa

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

People who intentionally starve themselves into an emaciated state yet remain convinced that they are overweight are suffering from a condition known as anorexia nervosa. Anorexia is a severe emotional disorder that is increasingly common, especially among young women in industrialized countries where cultural expectations encourage women to be thin. Fueled by popular fixations with thin and lean bodies, anorexia is also affecting a growing number of men, particularly athletes and those in the military. People with anorexia are terrified of becoming obese and refuse to maintain a normal weight, putting themselves in danger of starvation.

Anorexia rarely begins in people who are older than 40 years of age. It most commonly appears in the teenage years, affecting up to 3 in 100 adolescents. Although anorexia seldom emerges before puberty, associated mental conditions, such as depression and obsessive-compulsive behavior, are usually more severe when it does. The onset of anorexia is often preceded by a traumatic or stressful event and it is usually accompanied by other emotional difficulties. Anorexia is a life-threatening condition that can result in death from starvation, heart failure, electrolyte imbalance, or suicide.

There are two main types of anorexia nervosa:

Restricting Type -- characterized by dieting, fasting, or excessive exercise
Binge-Eating/Purging Type (anorexic-bulimic) -- characterized by self-induced vomiting or misuse of laxatives, enemas, or diuretics. Binge eating may or may not occur, and purging (vomiting) is common even after small amounts of food have been eaten. This type carries greater medical risk.

Signs and Symptoms

The primary sign of anorexia nervosa is severe weight loss, accompanied by any number of physical and psychological symptoms and unusual behaviors related to food, eating, or exercise. A person for whom a healthy weight would be 125 pounds, for example, may drop 20, or even as much as 60, pounds below this. At the same time, the person may insist that they are overweight.

Physical Signs

Scanty or absent menstrual periods
Thinning hair
Dry skin
Cold or swollen hands and feet
Bloated or upset stomach

Psychological Signs

Distorted perception of self (that is, a great difference between how an individual believes they look and their actual physical appearance)
Inability to remember things
Poor judgment
Refusal to acknowledge the gravity of the illness
Obsessive-compulsive behavior (excessive need to control personal environment)
Depression (feelings of ineffectiveness, loss of interest in friends and former activities, lack of spontaneity, rigid thinking, lack of initiative, flattened emotional response, irritability, insomnia, and diminished interest in sex)

Behavioral Symptoms

Unusual behaviors related to food or eating (for example, hoarding or concealing food, refusing to eat in public, eating only one type of food, ritually cutting food into tiny pieces, intense study of diets and calories, planning and preparing elaborate meals for others)
Compulsive exercising
Preoccupation with body size or body image
Preoccupation with weight control, dieting

Causes

There is no specific cause of anorexia. Medical experts agree that several factors work together in a complex fashion to lead to the eating disorder. These may include:

Severe trauma or emotional stress (such as the death of a loved one or sexual abuse) during puberty or prepuberty.
Abnormalities in brain chemistry. Changes in serotonin levels, a brain chemical that regulates appetite, may contribute to other symptoms of anorexia nervosa such as depression, impulsiveness, obsessive behaviors, or other mood disorders. In addition, the process of purging may deplete tryptophan, an amino acid necessary for the production of serotonin, leading to further imbalances.
A cultural environment that puts a high value on thin or lean bodies.
Overbearing, controlling, and critical parents who do not show emotional warmth.
A tendency toward perfectionism, fear of being ridiculed or humiliated, a desire to always be perceived as being "good." A belief that being perfect is necessary in order to be loved. Because perfection is impossible, the inability to attain perfection reinforces the person's sense of being unworthy of being loved. Not eating, according to some experts, is a passive act of revenge directed toward those who will never love the person because of his or her lack of perfection.
Family history of anorexia. About one-fifth of those with anorexia have a relative with an eating disorder. In fact, it is common to discover that someone with anorexia has a mother or sister with this eating disorder as well. If one identical twin has anorexia, the other has more than a 50% chance of also developing it. It is not clear, however, to what extent this family connection is due to heredity or to learned behavior.
Infection. Some researchers report an association between beta-hemolytic streptococcal infection, or Epstein Barr virus (the virus that causes mononucleosis), and development of anorexia.

Risk Factors

Age and gender -- anorexia is most common in teens and young adult women.
Early onset of puberty
Living in an industrialized country
Depression -- although depression is associated with the development of anorexia, it does not cause the disorder. Depression in a family member also appears to increase the likelihood of developing an eating disorder.
Obsessive-compulsive disorder (OCD) or other anxiety disorders -- OCD is present in up to two-thirds of people with anorexia. OCD associated with an eating disorder is often accompanied by a compulsive ritual around food (such as cutting it into tiny pieces). Phobia, another type of anxiety disorder that may also be present in someone with an eating disorder, and OCD tend to emerge before the eating disorder, while panic attacks may develop after the diagnosis is made.
Avoidant or narcissistic personality disorders -- approximately one-third of those with the restricting type of anorexia have avoidant personalities, which is characterized by feelings of inadequacy, social inhibition, extreme sensitivity to negative comments or criticism, and avoidance of interpersonal relationships, both at work and on an intimate level. Borderline personality disorder (exceptionally unstable interpersonal relationships, extremely poor self-image, and excessively impulsive behaviors) may be a risk factor as well, but such individuals are more likely to develop bulimia.
Participation in sports and professions that put emphasis on a lean body (such as dance, gymnastics, running, figure skating, horse racing, modeling, wrestling, acting)
Difficulty dealing with stress (pessimism, tendency to worry, refusal to confront difficult or negative issues)
History of sexual abuse or other traumatic event
Dieting

Diagnosis

While your doctor will rely on points discussed in Signs and Symptoms -- such as excessive weight loss, refusal to maintain normal body weight, and distorted self-perception -- the doctor will also ask a series of questions to better determine whether or not anorexia is present. The SCOFF questionnaire, developed in Great Britain, is proving to be a very reliable method for diagnosing anorexia. A "yes" response to at least two of the following questions is a strong indicator of an eating disorder:

S: "Do you feel sick because you feel full?"
C: "Do you lose control over how much you eat?"
O:"Have you lost more than 13 pounds recently?"
F: "Do you believe that you are fat when others say that you are thin?"
F: "Does food and thoughts of food dominate your life?"

If an eating disorder is suspected, the doctor will order several laboratory tests. These serve to determine blood count (to assess for signs of anemia that may be related to lack of iron or vitamin B12), levels of electrolytes (minerals such as potassium, calcium, and magnesium), amylase (serum amylase is elevated when there is frequent vomiting), and protein, and kidney, liver, and thyroid functions. Your doctor may also order an electrocardiogram (which gives a graphic record of the electrical activity of the heart). This may be abnormal if there is a deficiency in an electrolyte or nutrient such as potassium or calcium. If a diagnosis of anorexia is made, the doctor will require frequent office visits to monitor the condition. It is best for a person with anorexia to work with a multidisciplinary team including a doctor, a psychologist or psychiatrist, and a registered dietitian.

Preventive Care

The most effective prevention strategy is the development, from an early age, of healthy eating habits and a strong body image. Cultural values that place a premium on lean or thin bodies need to be questioned. Education about the life-threatening nature of anorexia is also an important part of prevention.

In those who have already been diagnosed and treated for anorexia, avoiding recurrence of the eating disorder is the primary goal.

Family and friends should be urged not to focus on the patient's condition or on issues of food or weight. Mealtimes, for example, should be reserved for social interaction and relaxation, without any discussion of the disease.
Careful and frequent monitoring of weight and other physical signs by the health care provider can reveal signs of a relapse.
Cognitive or other forms of psychotherapy can help the person to develop coping skills and change the unhealthy thought processes that underlie anorexia nervosa.
Family therapy is helpful in addressing underlying contributing factors in the home environment and in enlisting the support and understanding of family members.

Treatment

Anorexia demands a multi-pronged treatment plan that addresses both the physical and psychological aspects of this disorder. Cognitive-behavioral therapy, often in combination with antidepressants, is a very effective therapeutic approach for treatment of eating disorders. Complementary and alternative methods of treatment (such as the use of herbs and mind-body medicine) are valuable adjuncts to usual ways of stimulating appetite, addressing nutritional problems, and helping the patient to develop a healthier body image and to learn to deal more productively with stress.

In general, the most important aspect of treating anorexia is restoring weight and preventing starvation. Hospitalization may be necessary, particularly under the following circumstances:

Continuing weight loss, in spite of outpatient treatment
Body mass index (BMI) -- BMI is a measurement that takes into account a person's height and weight) 30% below normal. The normal range is a BMI of 19 - 24.
Irregular heart rhythm
Severe depression
Suicidal tendencies
Low potassium levels
Low blood pressure

Generally, adequate weight gain (1 - 2 pounds per week) and appropriate changes in behavior require a 10 - 12 week hospital stay. To avoid bloating, abdominal upset, and fluid retention, those who are severely malnourished are started on a diet of 1,500 calories a day, gradually increasing to as much as 3,500 calories. Because anorexia triggers changes in metabolism, high caloric intake may be necessary to stimulate weight gain.

Unfortunately, there is no completely effective treatment for anorexia nervosa, and recovery can take many years. Even after some weight gain, many people with anorexia remain quite thin and risk of relapse is very high. Several social influences may make recovery difficult:

Friends or family who express admiration or envy of the patient's thinness
Dance instructors or athletic coaches who put a premium on having a very lean body
Denial on the part of parents or other family members
A patient's persistent belief that emaciation is not only normal but also attractive and that purging is the only way to avoid becoming overweight

Involving friends, family members, and others in the treatment of the individual, with education for everyone regarding the gravity of the disease, may diminish these influences.

Lifestyle

Treating anorexia nervosa involves major lifestyle changes. The person must not only alter eating habits but also adjust their self perception to no longer hold a distorted body image. The following lifestyle changes may help in this process:

Establishing regular eating habits and a healthy diet
Developing a support system and participating in a support group for help with stress and emotional issues
Cutting back on exercise if obsessive exercise has been part of the disease. Once sufficient weight gain has been established, controlled exercise regimens can be a positive reinforcement for appropriate eating habits and a way to reduce gastrointestinal distress.

Medications

Anorexia nervosa in some ways resembles other major psychiatric disorders, such as depression and obsessive-compulsive disorder, because people with anorexia exhibit some of the symptoms of these disorders (for example obsessive behavior, lack of enjoyment from life, and severely distorted perception of reality, in this case, of the body). This has led to the use of antidepressants for anorexia, particularly selective serotonin reuptake inhibitors (SSRIs), because these drugs are first-line treatments for OCD and depression. Medications, however, may not work alone and should be used in conjunction with a multidisciplinary approach that includes nutritional interventions and psychotherapy.

Serotonin Reuptake Inhibitors

Fluoxetine

Studies suggest that fluoxetine may increase weight and improve mood over several months in people with anorexia nervosa and depression. Similarly positive results were obtained in a preliminary study of anorexics whose body weight had already been partly restored.

Tricyclic Antidepressants

This class of antidepressants, including imipramine and desipramine, tend to be more effective for bulimia than anorexia.

Clomipramine

One study suggests that clomipramine has the potential to stimulate weight gain and improve symptoms of anorexia.

Antihistamines

Cyproheptadine

In one study, using high doses of cyproheptadine hydrochloride, which is thought to stimulate appetite, decreased the number of days necessary to achieve appropriate weight gain and relieved depression in those with restricting type anorexia.

Hormones

Estrogen together with progesterone may help restore normal menstrual cycles. This, however, does not generally have any effect on weight.

Nutrition and Dietary Supplements

Anorexics with low body weight, low BMI, and low serum albumin (the main protein in blood) levels are at increased risk for vitamin and mineral deficiency. Vitamin abnormalities may contribute to cognitive difficulties such as poor judgment or memory loss and other psychiatric conditions. These deficiencies can often be corrected with dietary interventions.

There are natural therapies, including dietary supplements, that may help the general health and well-being of a person struggling with anorexia to become more balanced. Always tell your health care provider about the herbs and supplements you are using or considering using, as some supplements may interfere with conventional treatments.

Following these nutritional tips may help reduce symptoms:

Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily. However, do not fill up on water only.
Quality protein sources, such as organic meat and eggs, whey, and vegetable protein shakes, should be used as part of balanced program aimed at gaining muscle mass and preventing wasting. Talk with your health care provider about the best way for you to put on weight.
Try to avoid refined sugars, such as candy and soft drinks.

You may address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-vitamins and trace minerals, such as magnesium, calcium, zinc, and selenium.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 tablespoonful oil two to three times daily, to help decrease inflammation and improve immunity. Essential fatty acids play a critical role in brain function and hormone regulation, key health issues in the anorexic individual.
Vitamin C, 500 - 1,000 mg one to three times daily, as an antioxidant and for immune support.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, immune, and muscular support.
5-hydroxytryptophan (5-HTP), 50 mg two to three times daily, for mood stabilization.
Creatine, 5 - 7 grams daily, when needed for muscle weakness and wasting.
Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
L-glutamine, 500 - 1,000 mg three times daily, for support of gastrointestinal health and immunity.
Dihydroepiandosterone (DHEA), start at 5 mg three times a day and work up to 100 mg per day for 7 - 12 months for hormonal effects. It is recommended to use DHEA under the supervision of a qualified health care professional. If adverse effects develop, discontinue use.
Melatonin, 2 - 5 mg one hour before bedtime, for sleep and immune protection.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

Ashwagandha (Withania somniferum) standardized extract, 450 mg one to two times daily, for general health benefits and stress.
Fenugreek (Trigonella foenum-graecum), 250 - 500 mg two to three times daily, for appetite stimulation.
Cayenne pepper (Capsicum annuum) standardized extract, 400 mg three times daily, for digestive stimulation.
Milk thistle (Silybum marianum) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification support.
Fermented wheat germ extract, 1 packet dissolved in favorite beverage once daily, for immune effects and muscle gain.

Massage and Physical Therapy

Massage appears to be a helpful component of treatment for anorexia nervosa. Individuals using massage report lower anxiety levels and improved body image.

Homeopathy

A professional homeopath can provide supportive care to address various aspects of anorexia. Discuss homeopathy and anorexia with your health care provider.

Mind-Body Medicine

Cognitive Behavioral Therapy

Cognitive behavioral therapy is reported to be one of the most effective therapies for anorexia. It is based on the assumption that anorexia develops in response to life stresses. Treatment is aimed at confronting the individual's fears and avoidance behaviors and cultivating new problem-solving skills. It also aims to increase awareness of negative thought processes and to change them. Cognitive techniques are used to encourage patients to evaluate and challenge their automatic thoughts, examine their underlying assumptions, and replace them with realistic beliefs and actions based on reasonable self-expectations.

Family Therapy

Family therapy is recommended for both children and adults, in addition to individual therapy for the person with anorexia. Parents and other family members often have intense feelings of guilt and anxiety that they need to address. Family therapy is aimed, in part, at helping the parents or partner (in the case of an adult) understand the medical gravity of this illness and the ways in which they may be inadvertently contributing to it.

Hypnosis

Hypnosis has been reported to be successful as part of an integrated treatment program for anorexia nervosa. Hypnosis reportedly strengthens both self-confidence and the ability to cope, which may result in healthier eating, improved body image, and greater self-esteem.

Biofeedback

Studies suggest that biofeedback may be helpful in reducing stress in people with anorexia.

Other Considerations

Pregnancy

Anorexia poses several potential problems for women who are pregnant or wishe to become pregnant:

Difficulty getting pregnant and carrying a pregnancy to term because of higher rates of infertility and spontaneous abortion
Increased risk of low birth weight babies and birth defects
Malnourishment (particularly calcium deficiency) as the fetus grows
Increased risk of medical complications
Increased risk of relapse being triggered from the stress of pregnancy or parenthood

Prognosis and Complications

Medical complications associated with anorexia include:

Irregular heartbeat and heart attack
Anemia, often related to lack of vitamin B12
Low potassium, calcium, magnesium, and phosphate levels (particularly with binge-purge types)
Increased cholesterol
Hormonal changes (can lead to absence of menstrual periods, infertility, bone loss, and stunted growth)
Osteoporosis
Seizures and numbness in hands and feet
Disorganized thinking
Death (suicide is responsible for 50% of fatalities associated with anorexia)

The outlook for individuals with anorexia is variable, with recovery taking between 4 - 7 years. There is also a high chance of disease recurrence even after recovery. Long-term studies show that 50 - 70% of people recover from anorexia nervosa. However, 25% do not fully recover. Many, even after they are considered "cured," continue to exhibit traits of anorexia, such as remaining very thin and striving for perfection.

Supporting Research

Birmingham CL, Goldner EM, Bakan R. Controlled trial of zinc supplementation in anorexia nervosa. Int J Eating Disord. 1994;15:251-255.

Biederman J, Herzog DB, Rivinus TM, et al. Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 1985;5(1):10-16.

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Review Date:
10/19/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Crohn's disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)
Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

Click the icon to see an image of Crohn's disease.

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to build up on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both forms of inflammatory bowel disease have common genetic defects.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).
Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.
Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

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Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23,2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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