FitSugar

Top 10 Most Stressful Cities

FitSugar — Wed, 24 Sep 2008 14:30:00 -0700

Feeling stressed? It could be a sign of the times or it could also be a sign of where you live. Some cities are more stressful than others, and Forbes has outlined the top 10 most stressful cities in the US. They are:

Chicago, IL
New York, NY
Detroit, MI
Los Angeles, CA
San Francisco, CA
San Diego, CA
Cleveland, OH
Salt Lake City, UT
Providence, RI
Philadelphia, PA

Unfortunately, my beloved city by the bay is number five, and at times I can feel the pressures in the air. Do you live in one of the top 10 most stressful cities? If so, you may want to check out a few of my relaxation techniques to keep yourself cool under pressure.

Source

Stress

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Some people are pre-programmed for a heightened response to stress by conditions in the womb. Pregnant women under stress who eat a diet high in protein and low in carbohydrates have babies with higher cortisol levels. Later on, these levels increase in response to stress.
The impact of stress on the heart and circulation system is becoming more clear. Stress causes the body to release inflammatory markers that may worsen heart and circulatory diseases as well as inflammatory disease, such as rheumatoid arthritis. High levels of inflammatory markers are associated with increased risk of heart attack and stroke. Extreme stress can also produce a condition that mimics a heart attack, but is reversible. People under severe stress can experience irregular heart beats that make them susceptible to sudden cardiac death.
Stress also increases the risk of developing type 2 diabetes in women.
Traumatic stress has long been known to cause amnesia, emotional numbness, nightmares, and memory problems. Now it is known that traumatic emotional stress can cause permanent changes in the brain that interfere with the normal way information is accepted, coded, and retrieved.
The good news is that our physical response to stress is increasingly understood. Knowing what occurs at the cellular level may help researchers find more ways to counteract the detrimental physical and emotional effects of stress.

Introduction

Stress affects most people in some way. Acute (sudden, short-term) stress leads to rapid changes throughout the body. Almost all body systems (the heart and blood vessels, the immune system, the lungs, the digestive system, the sensory organs, and brain) gear up to meet the perceived danger.

These stresses could prove beneficial in a critical, life-or-death situation. Over time, however, repeated stressful situations put a strain on the body that may contribute to physical and psychological problems. Chronic (long-term) stress can have real health consequences and should be addressed like any other health concern.

Fortunately, research is showing that lifestyle changes and stress-reduction techniques can help people learn to manage their stress.

People can experience stress from external or internal factors.

External stressors include adverse physical conditions (such as pain or hot or cold temperatures) or stressful psychological environments (such as poor working conditions or abusive relationships). Humans, like animals, can also experience external stressors.
Internal stressors can also be physical (infections, inflammation) or psychological (such as intense worry about a harmful event that may or may not occur). As far as anyone can tell, internal psychological stressors are rare or absent in most animals except humans.

Stressors can also be defined as short-term (acute) or long-term (chronic).

Acute Stress. Acute stress is the reaction to an immediate threat, commonly known as the fight or flight response. The threat can be any situation that is perceived, even subconsciously or falsely, as a danger.

Common acute stressors include:

Noise (which can trigger a stress response even during sleep)
Crowding
Isolation
Hunger
Danger
Infection
High technology effects (playing video games, frequently ringing mobile phones)
Imagining a threat or remembering a dangerous event

Under most circumstances, once the acute threat has passed, levels of stress hormones return to normal. This is called the relaxation response.

Chronic Stress. Frequently, modern life poses ongoing stressful situations that are not short-lived. The urge to act (to fight or flee) must therefore be controlled. Stress, then, becomes chronic.

Common chronic stressors include:

On-going highly pressured work
Long-term relationship problems
Loneliness
Persistent financial worries

The Body's Response

The best way to envision the effect of acute stress is to imagine yourself in a primitive situation, such as being chased by a bear.

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 organizing systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate an area inside the brain called the amygdala, which appears to trigger an emotional response to a stressful event. In the case of the bear, this emotion is most likely fear.

Release of Neuropeptide S. The brain releases neuropeptide S, a small protein that modulates stress by decreasing sleep and increasing alertness and a sense of anxiety. This gives the person a sense of urgency to run away from the bear.

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, either to fight the bear or to flee from it. It also interferes with the ability to handle difficult 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 (such as the large bear) would be critical for avoiding such threats in the future.

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 effect on the immune system from confrontation with the bear is similar to organizing a defensive line of soldiers to potentially critical areas. The steroid hormones reduce the activity in parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be repositioned. These immune-boosting troops are sent to the body's front lines where injury or infection is most likely to occur, such as the skin and the lymph nodes.

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 stress effect moves blood flow away from the skin to support the heart and muscle tissues. This also reduces blood loss in the event that the bear causes a wound. The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Stress shuts down digestive activity, a nonessential body function during short-term periods of hard physical work or crisis.

Once the threat has passed and the effect has not been harmful (for example, the bear has not wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also return to normal.

Complications

In prehistoric times, the physical changes in response to stress were an essential adaptation for meeting natural threats. Even in the modern world, the stress response can be an asset for raising levels of performance during critical events, such as a sports activity, an important meeting, or in situations of actual danger or crisis.

If stress becomes persistent and low-level, however, all parts of the body's stress apparatus (the brain, heart, lungs, vessels, and muscles) become chronically over- or under-activated. Such chronic stress may produce physical or psychological damage over time. Acute stress can also be harmful in certain situations, particularly in individuals with preexisting heart conditions.

Studies suggest that the inability to adapt to stress is associated with the onset of depression or anxiety. In one study, two-thirds of subjects who experienced a stressful situation had nearly 6 times the risk of developing depression within that month.

Some evidence suggests that repeated release of stress hormones produces hyperactivity in the hypothalamic-pituitary-adrenal (HPA) system, and disrupts normal levels of serotonin, the nerve chemical that is critical for feelings of well-being. Some people appear to be more at risk for an overactive HPA system under stress, including those with the personality traits that cause perfectionism. Certainly, on a more obvious level, stress reduces the quality of life by reducing feelings of pleasure and accomplishment. In addition, relationships are often threatened in times of stress.

The full impact of mental stress on heart disease is just coming to light, but the underlying mechanisms are not always clear. Stress can certainly influence the activity of the heart when it activates the automatic part of the nervous system that affects many organs, including the heart. Such actions and others could theoretically affect the heart badly in several ways:

Sudden stress increases the pumping action and rate of the heart, while at the same time causing the arteries to constrict (narrow). This restricts blood flow to the heart. A 2002 study suggested that such actions may be responsible for some cases of acute stress that have been associated with a higher risk for serious heart problems. These problems include heart rhythm abnormalities and heart attacks, and even death in people with heart disease.
Emotional effects of stress alter the heart rhythms, which could pose a risk for serious arrhythmias (rhythm abnormalities) in people with existing heart rhythm disturbances.
Stress causes blood to become stickier (possibly in preparation of potential injury), increasing the likelihood of an artery-clogging blood clot.
Stress appears to impair the clearance of fat molecules in the body, raising blood-cholesterol levels, at least temporarily.
Stress that leads to depression appears to be associated with increased intima-medial thickness, a measure of the arteries that signifies worsening blood vessel disease.
Chronic stress may lead to the production of immune factors called cytokines, although study results vary widely. Cytokines produce an inflammatory response that is now believed to be responsible for damaging the arteries. Such damage contributes to heart disease. New studies indicate that some people under stress may have increased levels of C-reactive protein (CRP), a risk marker for heart attack. Each 1 mg/L increase in CRP has been linked to a 20% increased risk of myocaridal ischemia, a condition that signals poor blood flow to the heart muscle.
Stress causes the body to release inflammatory markers into the bloodstream. These markers may worsen heart disease or increase the risk of heart attack or stroke.
Studies have reported an association between stress and high blood pressure, which may be more pronounced in men than in women. According to some evidence, people who regularly experience sudden spikes in blood pressure (caused by mental stress) may, over time, develop injuries in the inner lining of their blood vessels. In one 20-year study, for example, men who periodically measured highest on the stress scale were twice as likely to have high blood pressure as those with normal stress.

Evidence is still needed to confirm any clear-cut relationship between stress and heart disease. For example, a 2002 study in Scotland found no greater risk for actual heart disease or heart events even in men who reported higher mental stress. In fact, higher stress was associated with fewer heart events. Men with high stress levels did tend to complain of chest pain and to go to the hospital for it more often than those with lower stress. They also went to the hospital more often.

Evidence links stress to heart disease in men, particularly in work situations where they lack control. The association between stress and heart problems in women is weaker, and there is some evidence that the ways women cope with stress may be more heart-protective. In one study, men were more apt than women to use alcohol or eat less healthily in response to stress, which might account for their higher heart risks from stress. Different stressors may affect genders differently. In one study, work stress was associated with a higher risk for heart disease in men, but marital stress -- not work stress -- was associated with more severe heart disease in women with existing heart problems.

A condition called stress cardiomyopathy (or Takotsubo cardiomyopathy) is widely recognized. In this disease, intense emotional or physical stress causes severe but reversible heart dysfunction. The patient experiences chest pain, and EKGs and echocardiograms indicate a heart attack, but further tests show no underlying obstructive coronary artery disease.

Acute emotional stress can create abnormal heartbeats. MRI studies show that asymmetric brain activity may play a role in making a stressed heart susceptible to ventricular arrhythmias by creating electrical instability. In some patients, this can cause sudden cardiac death.

Psychological stress is also recognized as a possible cause of acute coronary syndrome (ACS), a collection of symptoms that signify heart attack or approaching heart attack. In one study of men who suffered ACS at work or up to 2 hours after work, many of the men were found to have anger and negative emotions. A 2007 review of studies on blood qualities, coagulation, fibrinolysis, and platelet reactivity found that high levels of psychological stress are associated with harmful changes to the blood. The research suggests that stress has the potential to trigger ACS, particularly in patients with heart disease. The studies also suggest that the risk is greatest immediately after the stressful incident, rather than during it.

Stress Reduction and Heart Disease. Studies suggest that treatments that reduce psychological distress improve long-term outlook in people with heart disease, including after a heart attack. Evidence indicates that stress management programs may reduce the risk of heart attacks by up to 75% in people with heart disease. Specific stress management techniques may help some problems but not others. For example, acupuncture in one study helped people with heart failure but had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure.

One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people, prolonged or frequent mental stress causes an exaggerated increase in blood pressure.

Chronic stress affects the immune system in complicated ways, and may have various results.

Susceptibility to Infections. Chronic stress appears to blunt the immune system's response to infections, and may even impair a person's response to immunizations. Several studies have shown that people under chronic stress have low white blood cell counts and are vulnerable to colds. Once a person catches a cold or flu, stress can make symptoms worse. People who carry the herpes virus or HIV may be more susceptible to viral activation following exposure to stress. Even more serious, some research has found that HIV-infected men with high stress levels progress more rapidly to AIDS when compared to those with lower stress levels.

Inflammatory Response. Some evidence suggests that chronic stress triggers an over-production of certain immune factors called cytokines. In excess levels, these chemicals can have very damaging effects. A recent study found that students unable to cope with stress had high levels of TNF-alpha, an inflammatory cytokine. Such findings may partly explain the association between chronic stress and numerous diseases, including heart disease and asthma.

Whether or not stress causes or aggravates cancer is not entirely clear. One study reported no association between stressful life events and recurrence in women who had been treated for breast cancer. Nevertheless, some animal studies suggest that lack of control over stress (not simply stress itself) had negative effects on immune function and contributed to tumor growth.

That being said, a 2007 study found that stress activates a gene that may cause metastatic cancer, as measured by increasing levels of the marker AGR2.

Although stress reduction techniques have no effect on survival rates, studies show that they are very helpful in improving a cancer patient's quality of life. Stress is also known to be one cause of hyponatremia (low plasma sodium levels) in cancer patients. Fortunately, this imbalance can be corrected with drugs called AVP-receptor agonists, developed for use in heart failure.

The brain and intestines are strongly related, and are controlled by many of the same hormones and parts of the nervous system. Indeed, some research suggests that the gut itself has features of a primitive brain. It is not surprising then that prolonged stress can disrupt the digestive system, irritating the large intestine and causing diarrhea, constipation, cramping, and bloating. Excessive production of digestive acids in the stomach may cause a painful burning.

Irritable Bowel Syndrome. Irritable bowel syndrome (or spastic colon) is strongly related to stress. With this condition, the large intestine becomes irritated, and its muscular contractions are spastic rather than smooth and wave-like. The abdomen is bloated, and the patient experiences cramping and alternating periods of constipation and diarrhea. Sleep disturbances due to stress can make irritable bowel syndrome even worse.

Peptic Ulcers. It is now well-established that most peptic ulcers are either caused by the H. pylori bacteria or the use of nonsteroidal anti-inflammatory (NSAID) medications (such as aspirin and ibuprofen). Nevertheless, studies still suggest that stress may predispose someone to ulcers, or sustain existing ulcers. Some experts estimate that social and psychological factors play some contributing role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. In any case, some experts believe that the anecdotal relationship between stress and ulcers is so strong that attention to psychological factors is still warranted.

Inflammatory Bowel Disease. Although stress is not a cause of inflammatory bowel disease (Crohn's disease or ulcerative colitis), there are reports of an association between stress and symptom flare-ups. One study, for example, found that while short-term (over the previous month) stress did not significantly exacerbate ulcerative colitis symptoms, long-term perceived stress tripled the rate of flare-ups compared to patients who did not report feelings of stress.

Stress can have varying effects on eating problems and weight.

Weight Gain. Often stress is related to weight gain and obesity. Many people develop cravings for salt, fat, and sugar to counteract tension. As a result, they gain weight. Weight gain can occur even with a healthy diet, however, in some people exposed to stress. In addition, the weight gained is often abdominal fat, a predictor of diabetes and heart problems.

The release of cortisol, a major stress hormone, appears to encourage abdominal fat and may be the primary connection between stress and weight gain. Cortisol is a glucocorticoid. These hormones, along with insulin, appear to be responsible for stress-related food cravings. A 2005 study showed that hormonally induced cravings for "comfort foods" may have a biological benefit for managing stress. Eating comfort foods appears to reduce the negative hormonal and behavioral changes associated with stress, which might lessen the impact of stress on an individual. Carbohydrates in particular have been found to significantly increase levels of tryptophan and large neutral amino acids. This produces serotonin, which improves mood and performance under stress.

A 2007 study proposes a "reward-based stress eating" model. In this theory, stress and tasty, high-calorie foods cause the brain to make chemicals called endogenous opioids. These neurotransmitters help protect against the harmful effects of stress by slowing activity of a brain process called the hypothalamic-pituitary-adrenal (HPA) axis, thus weakening the stress response. Repeated stimulation of the reward pathways through stress-induced HPA stimulation, eating tasty food, or both, may lead to changes in the brain that cause compulsive overeating.

Weight Loss. Some people suffer a loss of appetite and lose weight during periods of stress. In rare cases, stress may trigger hyperactivity of the thyroid gland, stimulating appetite but causing the body to burn up calories at a faster than normal rate.

Eating Disorders. Chronically elevated levels of stress chemicals have been observed in patients with anorexia and bulimia. Some studies, however, have not found any strong link between stress and eating disorders. More work is needed to determine if changes in stress hormones are a cause or result of eating disorders.

Chronic stress has been associated with the development of insulin resistance, a condition in which the body is unable to use insulin effectively to regulate glucose (blood sugar). Insulin resistance is a primary factor in diabetes. In the Healthy Women Study, a large population of healthy women was studied for 15 years. Very stressful life events and severe depression greatly increased the risk of developing insulin resistance.

In another study of more than 33,000 Swedish workers, the development of type 2 diabetes was strongly correlated with work stress and low emotional support. However, the effect was seen in women, but not in men.

Stress can also exacerbate existing diabetes by impairing the patient's ability to manage the disease effectively.

Researchers are attempting to find the relationship between pain and emotion, but the area is complicated by many factors, including effects of personality types, fear of pain, and stress itself. A recent study suggests that chronic pain may impair the action of neutrophils, thereby weakening the immune response.

Muscular and Joint Pain. Stress may intensify chronic pain caused by arthritis and other conditions. According to a study on patients with rheumatoid arthritis, however, stress management techniques do not appear to have much effect on arthritic pain. Psychological distress also plays a significant role in the severity of back pain. Some studies have clearly associated job dissatisfaction and depression to back problems, although it is still unclear if stress is a direct cause of the back pain.

Headaches. Tension-type headaches are highly associated with stress and stressful events. Sometimes the headache does not start until long after the stressful event has ended. Additionally, stress can contribute to the development of headaches or cause headaches to occur more often.

Some research suggests that people who suffer from tension-type headaches may have some biological predisposition for translating stress into muscle contractions. Among the wide range of possible migraine triggers is emotional stress (although the headaches often erupt after the stress has eased). One study suggested that women with migraines tend to have personalities that over-respond to stressful situations.

The tensions of unresolved stress frequently cause insomnia, generally keeping the stressed person awake or causing awakening in the middle of the night or early morning. This appears to be due to the fact that stress causes physiological arousal during non-rapid eye movement (NREM) sleep.

Sexual Function. Stress can lead to diminished sexual desire and an inability to achieve orgasm in women. Stress response can cause androgen levels to drop, causing temporary impotence in men. Part of the stress response involves the release of brain chemicals that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis, which can prevent erection.

Premenstrual Syndrome. Some studies indicate that the stress response in women with premenstrual syndrome may be more intense than in those without the syndrome.

Fertility. Stress may even affect fertility. Stress hormones have an impact on the hypothalamus gland, which produces reproductive hormones. Severely elevated cortisol levels can even shut down menstruation. One small study reported a significantly higher incidence of pregnancy loss in women who had both high stress and prolonged menstrual cycles. Another reported that women with stressful jobs had shorter periods than women with low-stress jobs.

Effects on Pregnancy. Old wives' tales about a pregnant woman's emotions affecting her baby may have some credence. Stress may cause physiologic alterations, such as increased adrenal hormone levels or resistance in the arteries, which may interfere with normal blood flow to the placenta. Maternal stress during pregnancy has been linked to a higher risk for miscarriage, lower birth weights, and increased incidence of premature births. Some evidence also suggests that stress experienced by expectant mothers can even influence the way in which the baby's brain and nervous system will react to stressful events. Indeed, one study found a higher rate of crying and low attention in infants of mothers who had been stressed during pregnancy.

Menopause. A drop in estrogen levels during perimenopause and menopause may be responsible for changes in mood precipitated by stress. Estrogen replacement therapy can soften this response to stressful events.

Stress affects the brain, particularly memory, but the effects vary widely depending on whether the stress is acute or chronic.

Effect of Acute Stress on Memory and Concentration. Studies indicate that the immediate effect of acute stress impairs short-term memory, particularly verbal memory. On the plus side, high levels of stress hormone during short-term stress have been associated with enhanced memory storage and greater concentration on immediate events. The difference in effect may be due to how cortisol impacts glucocorticoid receptors in the hippocampus and prefrontal cortex. In a study of 20 men and 20 women, those whose cortisol levels increased in response to unpleasant, emotionally arousing photos had less memory recall later than those whose cortisol levels did not rise.

Effect of Chronic Stress on Memory. If stress becomes chronic, sufferers often experience loss of concentration at work and home, and they may become inefficient and accident-prone. In children, the physiologic responses to chronic stress can clearly inhibit learning. Chronic stress in older people may play an even more important role in memory loss than the aging process. In one study, for example, older adults with low stress hormone levels tested as well as younger adults in cognitive tests; those with higher stress levels tested 20 - 50% lower.

Studies have connected long-term exposure to excess amounts of cortisol (a major stress hormone) to shrinking of the hippocampus, the brain’s memory center. For example, two studies reported that groups who suffered from post-traumatic stress disorder (Vietnam veterans and women who suffered from sexual abuse) displayed up to 8% shrinking of the hippocampus. It is not yet known if this shrinking is reversible.

Allergies. Stress has been related to skin allergies. Some research suggests that stress, not indoor pollutants, may actually be a cause of the so-called sick-building syndrome. Sick-building syndrome produces allergy-like symptoms, such as eczema, headaches, asthma, and sinus problems, in office workers.

Compulsive Hoarding. People with obsessive-compulsive disorder (OCD) and compulsive hoarding are far more likely to have experienced a traumatically stressful event than people with OCD who are not hoarders. Hoarders who have experienced traumatic events have significantly more severe hoarding than those who have not been traumatized. The strongest association with traumatic stress is found in the clutter factor of compulsive hoarding, rather than in difficulty discarding objects.

Chronic Fatigue. Stress increases the risk of developing chronic fatigue syndrome, although studies suggest that high levels of emotional instability may genetically predispose someone to the syndrome.

Skin Disorders. Stress plays a role in worsening numerous skin conditions, including hives, psoriasis, acne, rosacea, and eczema, and is one of the most common causes of eczema. Unexplained itching may also be caused by stress. Evidence suggests that experiencing the stress of a traumatic event (parental divorce or separation, or a severe disease in a family member) before age 2 increases the risk of developing eczema.

Unexplained Hair Loss (Alopecia Areata). Alopecia areata is hair loss that occurs in localized (individual) patches. The cause is unknown, but stress is suspected as a player in this condition. For example, hair loss often occurs during periods of intense stress, such as mourning.

Teeth and Gums. Stress has now been implicated in increasing the risk for periodontal disease, which is disease in the gums that can cause tooth loss.

People under chronic stress often turn to alcohol abuse or tobacco use for relief. The damage these self-destructive habits cause under ordinary circumstances is compounded by the physiological effects of stress itself. Many people also resort to abnormal eating patterns or passive activities, such as watching television. The results of a national survey, released in February 2006, show that: "Americans engage in unhealthy behaviors such as comfort eating, poor diet choices, smoking and inactivity to help deal with stress."

Alcohol affects receptors in the brain that reduce stress. Lack of nicotine increases stress in smokers, which creates a cycle of dependency on smoking. One study indicated that nicotine has calming effects in women but not in men. In fact, in the study, smoking increased aggression in men.

The cycle is self-perpetuating: a sedentary routine, an unhealthy diet, alcohol abuse, and smoking all promote heart disease. They also interfere with sleep patterns, and lead to increased rather than reduced tension levels. Drinking four or five cups of coffee, for example, can cause changes in blood pressure and stress hormone levels similar to those produced by chronic stress. Animal fats, simple sugars, and salt are known contributors to health problems.

Conditions with Similar Symptoms

The physical symptoms of anxiety disorders mirror many symptoms of stress, including:

A fast heart rate
Rapid, shallow breathing
Increased muscle tension

Anxiety is an emotional disorder, however, and is characterized by feelings of apprehension, uncertainty, fear, or panic. Unlike stress, the triggers for anxiety are not necessarily or even usually associated with specific stressful or threatening conditions. Some individuals with anxiety disorders have numerous physical complaints, such as headaches, gastrointestinal disturbances, dizziness, and chest pain. Severe cases of anxiety disorders are debilitating, and interfere with career, family, and social spheres.

Depression can be a disabling condition, and, like anxiety disorders, may result from chronic stress. A 2005 study of Canadian workers found that individuals with a high level of work-related stress are more than twice as likely to experience a major depressive episode, compared with people under less stress. Evidence also suggests that certain people may be genetically susceptible to depression after stressful life events. Depression also mimics some of the symptoms of stress, including changes in appetite, sleep patterns, and concentration. Serious depression, however, is distinguished from stress by feelings of sadness, hopelessness, loss of interest in life, and, sometimes, thoughts of suicide. Acute depression is also accompanied by significant changes in the patient's functioning. Professional therapy may be needed in order to determine if depression is caused by stress, or if it is the primary problem.

Post-traumatic stress disorder (PTSD) is a reaction to a very traumatic event, and it is actually classified as an anxiety disorder. The event that brings on PTSD is usually outside the norm of human experience, such as intense combat or sexual assault. The patient struggles to forget the traumatic event and frequently develops emotional numbness and event-related amnesia. Often, however, there is a mental flashback, and the patient re-experiences the painful circumstance in the form of dreams and disturbing thoughts and memories. These thoughts and dreams resemble or recall the trauma. Other symptoms may include lack of pleasure in formerly enjoyed activities, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle-response to noise.

Treatment

Perhaps the best general approach for treating stress can be found in the elegant passage by Reinhold Niebuhr, "Grant me the courage to change the things I can change, the serenity to accept the things I can't change, and the wisdom to know the difference." The process of learning to control stress is life-long, and will not only contribute to better health, but a greater ability to succeed in one's own agenda.

Stress can be a factor in a variety of physical and emotional illnesses, which should be professionally treated. Many stress symptoms are mild and can be managed by over-the-counter medications (for example, aspirin, acetaminophen, or ibuprofen for tension headaches; antacids, anti-diarrhea medications, or laxatives for mild stomach distress). A physician should be consulted, however, for physical symptoms that are out of the ordinary, particularly those that get worse or wake a person up at night. A mental health professional should be consulted for unmanageable acute stress or for severe anxiety or depression. Often short-term therapy can resolve stress-related emotional problems.

In choosing specific strategies for treating stress, several factors should be considered.

No single method is always successful: A combination of approaches is generally most effective.
What works for one person does not necessarily work for someone else.
Stress can be positive as well as negative. Appropriate and controllable stress provides interest and excitement and motivates the individual to greater achievement. A lack of stress may lead to boredom and depression.

Stress may play a part in making people vulnerable to illness. A physician or psychologist should be consulted if there are any indications of accompanying medical or psychological conditions, such as heart symptoms, significant pain, anxiety, or depression.

People often succeed in relieving stress for the short term. However, they go back to previous ways of stressful thinking and behaving because of outside pressure, long-held beliefs, or habits. The following are some obstacles to managing stress:

The fight or flight urge: The very idea of relaxation can feel threatening, because it is perceived as letting down one's guard. For example, an over-demanding boss may put a subordinate into a psychological state of fighting-readiness, even though there is no safe opportunity for the subordinate to fight back or express anger. Stress builds up, but the worker has the illusion, even subconsciously, that the stress itself is providing safety or preparedness. For this reason, the employee does nothing to correct the condition.
Many people are afraid of being perceived as selfish if they engage in stress-reducing activities that benefit only themselves. The truth is that self-sacrifice (in the form of not reducing one’s stress) may be inappropriate and even damaging, if the person making the sacrifice is unhappy, angry, or physically unwell.
Some people believe that certain emotional responses to stress, such as anger, are natural and unchangeable features of personality. Research has shown, however, that with cognitive behavioral therapy, individuals can be taught to change their emotional reactions to stressful events.

It is essential to remember that reducing stress and staying relaxed clears the mind, so it can begin appropriate actions to get rid of the stress-ridden conditions.

Although treating stress cannot cure medical problems, stress management can be a very important part of medical treatment. Specific stress reduction approaches may benefit different medical problems. For example, acupuncture in one study helped reduce harmful heart muscle actions in people with heart failure, but it had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure. Stress reduction may improve well-being and quality of life for many patients who are experiencing stress because of severe or chronic medical conditions.

Important Note: Never use stress reduction techniques as the only treatment, or in place of proven treatments, for any medical condition.

Risk Factors

At some point in their lives virtually everyone will experience stressful events or situations that overwhelm their natural coping mechanisms. In one poll, 89% of respondents indicated that they had experienced serious stress in their lives. Some people are simply biologically prone to stress. Many outside factors influence susceptibility as well.

Conditions Most Likely To Produce Stress-Related Health Problems. Conditions that are most likely to be associated with stress and negative physical effects include the following:

An accumulation of persistent stressful situations, particularly those that a person cannot easily control (for example, high-pressured work plus an unhappy relationship)
Persistent stress following a severe acute response to a traumatic event (such as an automobile accident)
Acute stress accompanying serious illness, such as heart disease

Factors That Influence the Response to Stress. People respond to stress differently, depending on different factors:

Early nurturing: Abusive behavior towards children may cause long-term abnormalities in the hypothalamus-pituitary system, which regulates stress.
Personality traits: Certain people have personality traits that cause them to over-respond to stressful events.
Genetic factors: Some people have genetic factors that affect stress, such as having a more or less efficient relaxation response. One study found a genetic abnormality in serotonin regulation that was connected with a heightened reaction of heart rates and blood pressure in response to stress. (Serotonin is a brain chemical involved with feelings of well-being.)
Immune regulated diseases: Certain diseases that are associated with immune abnormalities (such as rheumatoid arthritis or eczema) may actually weaken a response to stress.
The length and quality of stressors: Naturally, the longer the duration and more intense the stressors, the more harmful the effects.

Individuals at Higher Risk for Stress. Studies indicate that the following people are more vulnerable to the effects of stress than others:

Older adults: As people age, achieving a relaxation response after a stressful event becomes more difficult. Aging may simply wear out the systems in the brain that respond to stress, so that they become inefficient. The elderly, too, are very often exposed to major stressors such as medical problems, the loss of a spouse and friends, a change in a living situation, and financial worries. No one is immune to stress, however, and it may simply go unnoticed in the very young and old.
Women in general and working mothers specifically: Working mothers, regardless of whether they are married or single, face higher stress levels and possibly adverse health effects, most likely because they bear a greater and more diffuse work load than men or other women. This has been observed in women in the U.S. and in Europe. Such stress may also have a domino and harmful effect on their children. It is not clear, however, if stress has the same adverse effects on women's hearts as it does on men's.
Less educated individuals.
Divorced or widowed individuals: Numerous studies indicate that unmarried people generally do not live as long as their married contemporaries.
Anyone experiencing financial strain, particularly long-term unemployed and those without health insurance.
People who are isolated or lonely.
People who are targets of racial or sexual discrimination.
People who live in cities.

Children are frequent victims of stress because they are often unable to communicate their feelings accurately. They also have trouble communicating their responses to events over which they have no control. Certain physical symptoms, notably repeated abdominal pain without a known cause, may be indicators of stress in children.

Various conditions can affect their susceptibility to stress.

Low Birth Weight. One study reported that low birth weight and slow growth up until age 7 was related to stress in adulthood.

Parental Stress. Parental stress, especially in mothers, is a particularly powerful source of stress in children, even more important than poverty or overcrowding. In a 2002 study, for example, young children of mothers who were highly stressed (particularly if they were depressed) tended to be at high risk for developing stress-related problems. This was especially true if the mothers were stressed during both the child's infancy and early years. Some evidence even supports the old idea that stress during pregnancy can have adverse effects on the infant's mood and behavior. Older children with stressed mothers may become aggressive and anti-social. One study suggested that stress-reduction techniques in parents may improve their children's behavior.

Gender Differences in Adolescent Stress. Adolescent boys and girls experience equal amounts of stress, but the source and effects may differ. Girls tend to become stressed from interpersonal situations, and stress is more likely to lead to depression in girls than in boys. For boys, however, specific events, such as changing schools or getting poor grades, appear to be the major sources of stress.

A report issued in October 2006 by the American Academy of Pediatrics recommends more unstructured play time for children. The report notes that today’s overscheduled, hurried lifestyle that many children experience is a source of stress and anxiety in some children.

In a 1999 study of 46,000 workers, health care costs were 147% higher in workers who were stressed or depressed than in others who were not. Furthermore, according to one survey, 40% of American workers describe their jobs as very stressful, making job-related stress an important and preventable health hazard.

Several studies are now suggesting that job-related stress is as great a threat to health as smoking or not exercising. Stress impairs concentration, causes sleeplessness, and increases the risk for illness, back problems, accidents, and lost time from work. Work stress can lead to harassment or even violence while on the job. At its most extreme, chronic stress places a burden on the heart and circulation that in some cases may be fatal. The Japanese even have a word for sudden death due to overwork, karoushi.

Not all work stress is harmful. However, studies suggest the following job-related stressors may increase people's -- particularly men's -- health risks:

Having no say in decisions that affect one's responsibilities
Unrelenting and unreasonable performance demands
Lack of effective communication and conflict-resolution methods among workers and employers
Lack of job security
Night-shift work, long hours, or both
Too much time spent away from home and family
Wages not matching levels of responsibility

Reducing Stress on the Job. Many institutions within the current culture, while paying lip service to stress reduction, put intense pressure on individuals to behave in ways that increase tension. Yet, there are numerous effective management tools and techniques available to reduce stress. Furthermore, treatment for work-related stress has proven benefits for both the employee and employer. In one study, at the end of 2 years, a company that instituted a stress management program saved nearly $150,000 in workers compensations costs (the cost of the program was only $6,000). Other studies have reported specific health benefits resulting from workplace stress-management programs. In one of the studies, workers with hypertension experienced reduced blood pressure after even a brief (16-hour) program that helped them manage stress behaviorally.

In general, however, few workplaces offer stress management programs, and it is usually up to the employee to find their own ways to reduce stress. Here are some suggestions:

Seek out someone in the Human Resources department or a sympathetic manager and communicate concerns about job stress. Work with them in a non-confrontational way to improve working conditions, letting them know that productivity can be improved if some of the pressure is off.
Establish or reinforce a network of friends at work and at home.
Restructure priorities and eliminate unnecessary tasks.
Learn to focus on positive outcomes.
If the job is unendurable, plan and execute a career change. Send out resumes or work on transfers within the company.
If this isn't possible, be sure to schedule daily pleasant activities and physical exercise during free time.

It may be helpful to keep in mind that bosses are also victimized by the same stressful conditions they are imposing. For example, in one study of male managers in three Swedish companies, those who worked in a bureaucracy had greater stress-related heart risks than those who worked in companies with social supports.

Caregivers of Family Members. Studies show that caregivers of physically or mentally disabled family members are at risk for chronic stress. One study reported that overall mortality rates were over 60% higher in caregivers who were under constant stress. Spouses caring for a disabled partner are particularly vulnerable to a range of stress-related health threats, including influenza, depression, heart disease, and even poorer survival rates. Caring for a spouse with even minor disabilities can induce severe stress.

Specific risk factors that put caregivers at higher risk for severe stress, or stress-related illnesses, include:

Caregiving wives: Some studies suggest that wives experience significantly greater stress from caregiving than husbands do.
Having a low income.
Being African-American: African-American people tend to be in poorer physical health, and have lower incomes, than Caucasians. They therefore face greater stress as caregivers to their spouses than their white counterparts.
Living alone with the patient.
Helping a highly dependent patient.
Having a difficult relationship with the patient.

Intervention programs that are aimed at helping the caregiver approach the situation positively can reduce stress, and help the caregiver maintain a positive attitude. A 2002 program also demonstrated that moderate-intensity exercise was very helpful in reducing stress and improving sleep in caregivers.

Health Professional Caregivers. Caregiving among the health professionals is also a high risk factor for stress. One study, for example, found that registered nurses with low job control, high job demands, and low work-related social support experienced very dramatic health declines, both physically and emotionally.

People who are less emotionally stable or have high anxiety levels tend to experience specific events as more stressful than others. Some doctors describe an exaggerated negative response to stress as "catastrophizing" the event (turning it into a catastrophe). Nevertheless, a 2003 study of patients with anxiety disorder did not find any differences in actual physical response to stress (heart rate, blood pressure, release of stress hormones) compared to people without anxiety.

The lack of an established network of family and friends predisposes one to stress disorders and stress-related health problems, including heart disease and infections. A study, meanwhile, reported that older people who maintain active relationships with their adult children are buffered against the adverse health effects of chronic stress-inducing situations, such as low income or lower social class. Another study suggested this may be because people who live alone are unable to discuss negative feelings as a means to relieve their stress.

Studies of people who remain happy and healthy despite many life stresses conclude that most have very good networks of social support. One study indicated that support even from strangers reduced blood pressure surges in people undergoing a stressful event. Many studies suggest that having a pet helps reduce medical problems aggravated by stress, including heart disease and high blood pressure.

Lifestyle Changes

A healthy lifestyle is an essential companion to any stress-reduction program. General health and stress resistance can be enhanced by regular exercise, a diet rich in a variety of whole grains, vegetables, and fruits, and by avoiding excessive alcohol, caffeine, and tobacco.

Of interest, a 2003 study suggested that fish oil, which has been associated with a lower risk for heart disease and stroke, may blunt some of the harmful effects of mental stress on the heart.

In one study, high doses of vitamin C reduced stress levels and blood pressure. The doses given were higher than the recommended upper limit of 2,000 mg per day. High doses may cause headaches and diarrhea. Long-term use increases risk for kidney stones and has other adverse effects in specific individuals.

Exercise in combination with stress management techniques is extremely important for many reasons:

Exercise is an effective distraction from stressful events.
Exercise may directly blunt the harmful effects of stress on blood pressure and the heart (exercise protects the heart in any case).

Usually, a varied exercise regime is more interesting, and thus easier to stick to. Start slowly. Strenuous exercise in people who are not used to it can be very dangerous and any exercise program should be discussed with a physician. In addition, half of all people who begin a vigorous training regime drop out within a year. The key is to find activities that are exciting, challenging, and satisfying. The following are some suggestions:

Sign up for aerobics classes at a gym.
Brisk walking is an excellent aerobic exercise that is free and available to nearly anyone. Even short brisk walks can relieve bouts of stress.
Swimming is an ideal exercise for many stressed people, including pregnant women, individuals with musculoskeletal problems, and those who suffer exercise-induced asthma.
Yoga or Tai Chi can be very effective, combining many of the benefits of breathing, muscle relaxation, and meditation while toning and stretching the muscles. The benefits of yoga may be considerable. Numerous studies have found it beneficial for many conditions in which stress is an important factor, such as anxiety, headaches, high blood pressure, and asthma. It also elevates mood and improves concentration and the ability to focus.

As in other areas of stress management, making a plan and executing it successfully develops feelings of mastery and control, which are very beneficial in and of themselves. Start small. Just 10 minutes of exercise three times a week can build a good base for novices. Gradually build up the length of these every-other-day sessions to 30 minutes or more.

Cognitive-behavioral techniques (CBT) are among the most effective ways of reducing stress. A 2005 study found that CBT training can have a long-term impact one’s ability to cope with stress. In the study, participants received CBT training and were exposed to a stressful situation 4 months later. The participants who had received CBT training had significantly less stress-induced cortisol responses compared with individuals who had received no stress management training. This effect was observed in both men and women, although the CBT had a greater effect on men. CBT may be particularly helpful when the source of stress is chronic pain or a chronic disease. In fact, in a study of patients with HIV, CBT was more helpful than support groups for improving well-being and quality-of-life.

A typical CBT approach includes identifying sources of stress, restructuring priorities, changing one's response to stress, and finding methods for managing and reducing stress.

Identifying Sources of Stress. One key component in most CBT approaches is a diary that keeps an informal inventory of daily events and activities. While this exercise might itself seem stress producing (and yet one more chore), it need not be done in painstaking detail. A few words accompanying a time and date are usually enough to serve as reminders of significant events or activities.

The first step is to note activities that put a strain on energy and time, trigger anger or anxiety, or precipitate a negative physical response (such as a sour stomach or headache).

Also note positive experiences, such as those that are mentally or physically refreshing or produce a sense of accomplishment.

After a week or two, try to identify two or three events or activities that have been significantly upsetting or overwhelming.

Questioning the Sources of Stress. Individuals should then ask themselves the following questions:

Do these stressful activities meet my goals or someone else's?
Have I taken on tasks that I can reasonably accomplish?
Which tasks are under my control and which ones aren't?

Restructuring Priorities: Adding Stress Reducing Activities. The next step is to attempt to shift the balance from stress-producing to stress-reducing activities. Eliminating stress is rarely practical or feasible, but there are many ways to reduce its impact.

Consider as many relief options as possible. Examples include:

Listen to music. Music is an effective stress reducer in both healthy individuals and people with health problems. In one study, for example, students who listened to a well-known gentle classical piece of music during a stressful task had reduced feelings of anxiety, heart rate, and blood pressure.
Take long weekends or, ideally, vacations.
If the source of stress is in the home, plan times away, even if it is only an hour or two a week.
Replace unnecessary time-consuming chores with pleasurable or interesting activities.
Make time for recreation. This is as essential as paying bills or shopping for groceries.
Own a pet. In a study of people with high blood pressure, pet owners had much lower blood pressure increase in response to stress than non-owners. Note that owning a pet was beneficial only for people who like animals to begin with.

Discuss Feelings. The concept of communication and letting your feelings out has been so excessively promoted and parodied that it has nearly lost its value as good psychological advice. Nevertheless, feelings of anger or frustration that are not expressed in an acceptable way may lead to hostility, a sense of helplessness, and depression.

Expressing feelings does not mean venting frustration on waiters and subordinates, boring friends with emotional minutia, or wallowing in self-pity. In fact, because blood pressure may spike when certain chronically hostile individuals become angry, some therapists strongly advise that just talking, not simply venting anger, is the best approach, especially for these people.

The primary goal is to explain and assert one's needs to a trusted individual in as positive a way as possible. Direct communication may not even be necessary. Writing in a journal, writing a poem, or composing a letter that is never mailed may be sufficient.

Expressing one's feelings solves only half of the communication puzzle. Learning to listen, empathize, and respond to others with understanding is just as important for maintaining the strong relationships necessary for emotional fulfillment and reduced stress.

Keep Perspective and Look for the Positive. Reversing negative ideas and learning to focus on positive outcomes helps reduce tension and achieve goals. The following steps, using an example of a person who is alarmed at the prospect of giving a speech, may be useful:

First, identify the worst possible outcomes (forgetting the speech, stumbling over words, humiliation, audience contempt).
Rate the likelihood of these bad outcomes happening (probably very low or that speaker wouldn't have been selected in the first place).
Envision a favorable result (a well-rounded, articulate presentation with rewarding applause).
Develop a specific plan to achieve the positive outcome (preparing in front of a mirror, using a video camera or tape recorder, relaxation exercises).
Try to recall previous situations that initially seemed negative but ended well.

Use Humor. Research has shown that humor is a very effective mechanism for coping with acute stress. Keeping a sense of humor during difficult situations is a common recommendation from stress management experts. Laughter not only releases the tension of pent-up feelings and helps keep perspective, but it appears to have actual physical effects that reduce stress hormone levels. It is not uncommon for people to recall laughing intensely even during tragic events, such as the death of a loved one, and to remember this laughter as helping them to endure the emotional pain.

Relaxation Methods. Since stress is here to stay, everyone needs to develop methods to promote the relaxation response, the natural unwinding of the stress response. Relaxation lowers blood pressure, respiration, and pulse rates, releases muscle tension, and eases emotional strains. This response is highly individualized, but there are certain approaches that seem to work.

Combinations are probably best. For example, in a study of children and adolescents with adjustment disorder and depression, a combination of yoga, a brief massage, and progressive muscle relaxation effectively reduced both feelings of anxiety and stress hormone levels. A 2005 study of organ transplant recipients showed that training in meditation and gentle yoga led to significant improvements in quality of sleep and lessened anxiety and depression.

No one should expect a total resolution of stress from these approaches, but if done regularly, these programs can be very effective.

Acupuncture. Some evidence suggests that acupuncture may also be helpful. It might even improve some physical factors associated with stress and health problems. For example, in a study of heart failure patients, acupuncture improved stress-related heart muscle activity, which could be an important benefit in these patients. However, acupuncture had no effect on stress-related blood pressure or heart rate.

Hypnosis. Hypnosis may also benefit some people with severe stress. In one study of patients with irritable bowel, stress reduction by hypnosis correlated with improvement in many bowel symptoms.


*Deep Breathing Exercises.* During stress, breathing becomes shallow and rapid. Taking a deep breath is an automatic and effective technique for winding down. Deep breathing exercises consciously intensify this natural physiologic reaction and can be very useful during a stressful situation, or for maintaining a relaxed state during the day.	Inhale through the nose slowly and deeply to the count of 10. Make sure that the stomach and abdomen expand, but the chest does not rise. Exhale through the nose, slowly and completely, also to the count of 10. To help quiet the mind, concentrate fully on breathing and counting through each cycle. Repeat five to 10 times, and make a habit of doing the exercise several times each day, even when not feeling stressed.
*Muscle Relaxation.* Muscle relaxation techniques, often combined with deep breathing, are simple to learn and very useful for getting to sleep. In the beginning it is useful to have a friend or partner check for tension by lifting an arm and dropping it. The arm should fall freely. Practice makes the exercise much more effective and produces relaxation much more rapidly. Small studies have reported beneficial effects on blood pressure in patients with high blood pressure who use this technique.	After lying down in a comfortable position without crossing the limbs, concentrate on each part of the body. Maintain a slow, deep breathing pattern throughout this exercise. Tense each muscle as tightly as possible for a count of five to 10, and then release it completely. Experience the muscle as totally relaxed and lead-heavy. Begin with the top of the head and progress downward to focus on all the muscles in the body. Be sure to include the forehead, ears, eyes, mouth, neck, shoulders, arms and hands, fingers, chest, belly, thighs, calves, and feet. Once the external review is complete, imagine tensing and releasing internal muscles.
*Meditation.* Meditation, used for many years in Eastern cultures, is now widely accepted in this country as a relaxation technique. The goal of all meditative procedures, both religious and therapeutic, is to quiet the mind (essentially, to relax thought). Small studies have suggested that regular meditation can benefit the heart and help reduce blood pressure. Better research is needed, however, to confirm such claims. Some recommend meditating for no longer than 20 minutes in the morning after awakening and then again in early evening before dinner. Even once a day is helpful. Note: Meditating before going to bed may cause some people to wake up in the middle of the night, alert and unable to return to sleep. New practitioners should understand that it can be difficult to quiet the mind, and should not be discouraged by lack of immediate results. Several techniques are available. A few are discussed here. The only potential risks from meditating are in people with psychosis, in whom meditating may trigger a psychotic event.	Mindfulness Meditation. Mindfulness is a common practice that focuses on breathing. It employs the basic technique used in other forms of meditation. Sit upright with the spine straight, either cross-legged or sitting on a firm chair with both feet on the floor, uncrossed. With the eyes closed or gently looking a few feet ahead, observe the exhalation of the breath. As the mind wanders, simply note it as a fact and returns to the "out" breath. It may be helpful to imagine your thoughts as clouds dissipating away. Transcendental Meditation (TM). TM uses a mantra (a word that has a specific chanting sound but no meaning). The person meditating repeats the word silently, letting thoughts come and go. In one study, TM was as effective as exercise in elevating mood. Mini-Meditation. The method involves heightening awareness of the immediate surrounding environment. Choose a routine activity when alone. For example: While washing dishes, concentrate on the feel of the water and dishes. Allow the mind to wander to any immediate sensory experience (sounds outside the window, smells from the stove, colors in the room). If the mind begins to think about the past or future, or fills with unformed thoughts or worries, redirect it gently back. This redirection of brain activity from your thoughts and worries to your senses disrupts the stress response and prompts relaxation. It also helps promote an emotional and sensual appreciation of simple pleasures already present in a person's life.
*Biofeedback.* Biofeedback is a technique that measures bodily functions, like breathing, heart rate, blood pressure, skin temperature, and muscle tension. By watching these measurements, you can learn how to alter these functions by relaxing or holding pleasant images in your mind.	During biofeedback, electric leads are taped to a subject's head. The person is encouraged to relax using methods such as those described above. Brain waves are measured and an audible signal is emitted when alpha waves are detected, a frequency which coincides with a state of deep relaxation. By repeating the process, subjects associate the sound with the relaxed state and learn to achieve relaxation by themselves.
*Massage Therapy.* A 2005 report that reviewed data from multiple studies showed that massage therapy decreases cortisol levels. Another 2005 study showed that massage from a stable romantic partner can reduce physiological responses to a subsequent stressful event. In the study, women who received instructed shoulder-neck-massage from their partners before being exposed to stress had lowered cortisol responses, and smaller heart rate increases after the stressful event. Interestingly, massage was more beneficial than receiving social support from the partner, indicating the power of physical touch in managing stress. Several massage therapies are available.	Many massage techniques are available, such as the following: Swedish massage is the standard massage technique. It uses long smooth strokes, and kneading and tapping of the muscles. Shiatsu applies intense pressure to the same points targeted in acupuncture. It can be painful, but people report deep relaxation afterward. Reflexology manipulates acupuncture points in the hands and feet.

Some people who experience chronic stress seek herbal or natural remedies. It should be strongly noted, however, that just as with standard drugs, so-called natural remedies can cause problems, sometimes serious ones.

Probiotics. Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria. They do so through various mechanisms, such as excreting certain acids (for example, lactate, acetate) that inhibit harmful bacteria. They may also compete with them for nutrients. Stress reduces levels of these bacteria. Research even suggests that probiotics may help maintain remission in patients with IBD. In one small study, people suffering from stress and exhaustion significantly reduced their stress symptoms and gastrointestinal complaints when they took a probiotic supplement for 6 months. The specific bacteria that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Aromatherapy. The smell of lavender has long been associated with a calming effect. In a Japanese study, 14 women who were put in a room with a lavender scent experienced reduced mental stress. Several aromatherapies are now used for relaxation. Use caution, however, as some of the exotic plant extracts in these formulas have been associated with a wide range of skin allergies.

Valerian. Valerian is an herb that has sedative qualities and may reduce stress and associated physical effects. This herb is on the FDA's list of generally safe products. Of note, however, the herb's effects could be dangerously increased if it is used with standard sedatives. Other interactions and long-term side effects are unknown. Side effects include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, however, 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 numerous 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.

Special Warning on Kava. Kava has been commonly used to reduce anxiety and stress. It is now highly associated with liver injury and even liver failure in a few cases. Experts now strongly warn against its use.

People seeking relief from stress should be wary of things that promise a quick cure, or plans that include the purchase of expensive treatments. These treatments may be useless and sometimes even dangerous.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.nami.org -- National Alliance for the Mentally Ill
www.nmha.org -- National Mental Health Association
www.amtamassage.org -- American Massage Therapy Association
www.cognitivetherapynyc.com -- American Institute for Cognitive Therapy
www.aabt.org -- Association for the Advancement of Behavior Therapy
www.healthyminds.org -- The American Psychiatric Association
www.naswdc.org -- The National Association of Social Workers
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.stress.org -- The American Institute of Stress

References

Ginsburg KR and the Committee on Communications and Committee on Psychosocial Aspects of Child and Family Health. Clinical Report: The Importance of Play in Promoting Healthy Child Development and Maintaining Strong Parent-ChildBonds.Last accessed on 17 October, 2006.

Dallman MF, Pecoraro NC, la Fleur SE. Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav Immun. 2005;19:275-280.

Wang J. Work stress as a risk factor for major depressive episode(s). Psychol Med. 2005;35:865-871.

Hammerfald K, Grau M, et al. Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects-A randomized controlled trial. Psychoneuroendocrinology. 2005 Sep 22; epub ahead of print.

Kreitzer MJ, Gross CR, Ye X, et al. Longitudinal impact of mindfulness meditation on illness burden in solid-organ transplant recipients. Prog Transplant. 2005;15:166-172.

Field T, Hernandez-Reif M, Diego M, et al. Cortisol decreases and serotonin and dopamine increase following massage therapy. Int J Neurosci. 2005;115:1397-1413.

Ditzen B, Neumann I, Bodenmann G, et al. Romantic Partner Interaction Reduces Endocrine and Autonomic Stress Responses in Women. New Research Abstracts, Annual Meeting of the American Psychiatric Association. Washington, D.C. 2005. Abstract NR140.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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.

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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

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.

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.

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.

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.

Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007 Apr 18;297(15):1683-96.

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.

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

adam.com

Asthma in children and adolescents

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

In This Report

Highlights
Introduction
Causes
Prognosis
Risk Factors
Symptoms
Diagnosis
Treatment
Quick-Relief Medications...
Long-Term Relief Medication...
Other Treatments
Managing Asthma
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

In 2007, the FDA requested the manufacturers of omalizumab (Xolair) to include a “boxed warning” emphasizing that this drug may cause a severe and life-threatening allergic reaction (anaphylaxis). Health care providers need to carefully observe patients for 2 hours after they receive an omalizumab injection. However, because an allergic reaction can occur up to 24 hours after the injection, patients need to know the signs and symptoms of anaphylaxis and how to self-administer emergency treatment. Omalizumab is approved for patients ages 12 and older who have moderate-to-severe asthma related to allergies.

Drug Approval

In 2006, budesonide/formoterol (Symbicort) was approved for patients age 12 years and older. Symbicort combines a corticosteroid and a long-acting beta2-agonist into a single inhaler.

Inhaled Corticosteroids

Inhaled corticosteroids may help reduce wheezing in young children with breathing problems, but they do not help prevent the development of asthma, according to several 2006 studies in the New England Journal of Medicine.
Inhaled corticosteroids work better than a corticosteroid/long-acting beta2-agonist combination or a leukotrine receptor antagonist drug in treating children with mild-to-moderate asthma, suggests a 2007 study in the Journal of Allergy and Clinical Immunology.

Long-Acting Beta2-Agonists

Long-acting beta2-agonist drugs such as salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer) may worsen asthma symptom severity and increase the risk for asthma-related death, indicates a 2006 review in the Annals of Internal Medicine.
Products that contain salmeterol and formoterol now have strengthened warning labels detailing these risks.

Childhood Asthma Statistics

Asthma death rates among children have largely declined since 1999 while doctors’ office visits for asthma treatment have more than doubled, indicates a recent report from the U.S. Centers for Disease Control and Prevention.

Introduction

The word asthma originates from an ancient Greek word meaning panting. Essentially, asthma is an inability to breathe properly. When any person inhales, the air travels through the following structures:

Air passes into the lungs and flows through progressively smaller airways called bronchioles. The lungs contain millions of these airways.
All bronchioles lead to alveoli, which are microscopic sacs where oxygen and carbon dioxide are exchanged.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Asthma is a chronic condition in which these airways undergo changes when stimulated by allergens or other environmental triggers. Such changes appear to be two specific responses:

The hyperreactive response (also called hyperresponsiveness)
The inflammatory response

These actions in the airway cause patients to cough, wheeze, and experience shortness of breath (dyspnea), the classic symptoms of asthma.

In the hyperreactive response, smooth muscles in the airways constrict and narrow excessively in response to inhaled allergens or other irritants. Airways in everyone's lungs respond by constricting when exposed to allergens or irritants but there are major differences in the hyperreactive response that occurs in people with asthma:

When people without asthma breathe in and out deeply, the airways relax and open in order to rid the lungs of the irritant.
When people with asthma try to take those same deep breaths, their airways do not relax but instead narrow, causing the patients to pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps a deficiency in a critical chemical that prevents the muscles from relaxing.

The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:

The immune system responds to allergens or other environmental triggers by delivering white blood cells and other immune factors to the airways.
These so-called inflammatory factors cause the airways to swell, fill with fluid, and produce a thick sticky mucus.

Click the icon to see an image of a normal versus asthmatic bronchiole.

This combination of events results in wheezing, breathlessness, inability to exhale properly, and a phlegm-producing cough.

Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.

Causes

Asthma occurs in about 5 million American children. Each year about 200,000 of them are hospitalized. It is the most common chronic childhood illness. About half of all cases of asthma develop before the age of 10, and about 80% of patients develop symptoms before they are 5 years old.

The mechanisms that cause asthma are complex and vary among population groups and even individuals. For example, asthma in children is highly associated with allergies. However, only a minority of children with allergies have asthma, and allergic response cannot explain all cases of asthma. Other factors, such as genetics or environmental conditions are probably involved in the development of asthma. Most likely, several genes combine to make a child susceptible to environmental triggers, not only allergens but also possibly infections, dietary patterns, or air pollution. Physical factors, particularly having smaller lungs, affect the chances for later asthma.

Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma also have allergies. Some studies suggest that children who have allergies are also at greater risk for developing asthma as adults. A 2006 study found that children who are allergic to dust mites are three times more likely to later develop asthma than children who were not allergic.

However, the evidence is clearly mixed. Several other 2006 studies suggested that avoiding dust mites does not help prevent asthma and, in fact, early exposure to dust mites may even protect children from developing asthma and allergic responses. Some experts think that giving immunotherapy (“allergy shots”) to children with allergies may help prevent asthma development.

An asthma attack can be induced or aggravated by direct irritants to the lungs. Studies indicate that the more indoor allergens a child is allergic to, the higher the risk for severe asthma. Important irritants or allergens include the following:

Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
Animal dander. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems.
Molds.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons because they cause seasonal changes (and pollen) to start earlier.
Food allergies. About 8 - 10% of children with asthma also have food allergies. These children also appear to have a high risk for very serious reactions to such foods. In infants and toddlers, allergy to eggs appears to be a predictor of asthma.
Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. In people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

The Allergic Response. The allergic process, called atopy, and its connection to asthma are not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways. One description is as follows:

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
Interleukins 4, 9, and 13, for example, may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

Researchers are investigating the role that T cells play in asthma. T cells are white blood cells that are involved in the immune response. Researchers had focused on the T cell called type 2 helper (ThH2) cells. However, a 2006 breakthrough study in the New England Journal of Medicine suggested that a different type of T cell may play a stronger role in asthma than previously thought.

Researchers discovered that these cells, called natural killer T cells, are far more common in the lungs of people with asthma than in the lungs of healthy people. Natural killer T cells are very rare, but researchers found them in 60% of people with moderate-to-severe persistent asthma. While this research is preliminary, it may explain why corticosteroid drugs do not work well for some patients with asthma: Steroid drugs target Th2 and other inflammatory cells, not natural killer T cells. Researchers think that further investigation of natural killer T cells may lead the way to new types of asthma drugs. If these cells prove to be involved in asthma, then drugs that eliminate them might become an important new treatment.

Over the course of years the repetition of the inflammatory events involved in asthma can cause irreversible structural and functional changes in the airways, a process called remodeling. The remodeled airways are persistently narrow and can cause chronic asthma. Researchers are trying to determine how this process occurs:

Interleukins. Some researchers are looking at potent immune factors, including interleukins 11 and 13. They have been linked to a number of processes possibly involved in remodeling, including scarring in the airways and overgrowth of cells in the smooth muscles that line the airways.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings and some researchers believe it may be major factor in remodeling.

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to be passed to children from the mother than from the father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Research on the genetics of these conditions is confusing. Of some significant promise, researchers have identified a gene (ADAM33), which has been linked to asthma. The gene regulates one of the enzymes called metalloproteases, which are involved with the smooth muscle in the airway. A mutation of this gene could play a role in airway changes that occur after inflammation.

The role of early childhood respiratory and intestinal infections is very complex. Viral respiratory infections certainly worsen existing asthma, but the most common ones are unlikely to be causes of childhood asthma. In fact, early respiratory and intestinal infections may offer some protection against asthma.

Early Respiratory Infections as Causes of Asthma. Studies suggest that most respiratory infections are not important causes of asthma in children, except in certain cases. An important exception is the respiratory syncytial virus (RSV), which has been implicated in the development of asthma. RSV is the major viral cause of infant pneumonia. Studies also indicate that infants who have reduced lung function within a few days after birth are at increased risk of developing asthma by the time they are 10 years old.

Common Respiratory Infections Worsen Asthma. Common respiratory infections viruses that cause colds (such as the rhinovirus) may in some cases be associated with the development of asthma. A 2007 study suggested that children who have a wheezing rhinovirus during infancy are at increased risk for developing asthma by age 6. Even if these viruses do not directly cause asthma, they can worsen asthma in children who already have it. Rhinovirus has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma worsening in children. Some research suggests that colds promote inflammation in patients with existing asthma and increase the intensity of airway responsiveness for weeks.

The Hygiene Theory: Early Infections as Protection Against Asthma. Another blames the dramatic increase in asthma on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections stimulate production of specific immune factors called Th1 cells. As these cells build up, they replace other immune factors called Th2 cells, which react to allergens -- a less serious threat to the body. Without infections to stimulate the production of the Th1 infection fighters, the Th2 allergen fighters are not replaced, and they persist at high levels, making the growing child more susceptible to allergies and asthma.

A number of different studies support this theory:

Some studies suggest that being part of a large family or attending day care increases the risk for early respiratory infections but reduces the risk of childhood asthma. The occasional cold, then, may be protective.
In one study, researchers measured levels of bacterial byproducts called endotoxins in the mattress dust of 812 children. Those with the highest levels had 80% lower rates in allergies and asthma.
Another study further found a strong association between allergy development and the absence of certain beneficial bacteria (called probiotics) carried in the infant's intestines. Infants who were born in more hygienic environments tended to lack these bacteria. Antibiotic overuse and modern hygiene may be reducing these helpful organisms. (Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.)

The standard vaccinations against serious childhood infections, according to several important studies, pose no risk for asthma. One of the studies even reported some lower risk for asthma and allergies in the second and third years after vaccinations. Infections killed thousands of children every year before immunization became widespread. Asthma, although serious, is rarely fatal in children. No one should stop giving their children vaccinations against childhood killers.

GERD. At least half of patients with asthma also have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux which causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerve, which runs through the gastrointestinal tract. This stimulated nerve, in turn, triggers the nearby airways in the lung to constrict, causing asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be suspected as a contributor in the following patients:

Those who do not respond to asthma treatments.
Those whose asthma attacks follow episodes of heartburn.
Those whose attacks are worse after eating or exercise.
Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in patients with asthma.)

Treating GERD symptoms with anti-acid drugs may resolve asthma in some (but not all) patients who share both conditions. A small 2005 observational study found that while GERD was common in patients with asthma, treatment of GERD had no effect on asthma symptoms. [See In-Depth Report #85: Heartburn and gastroesophageal reflux disease.]

Sinusitis. Almost half of children and adults with allergic asthma have sinus abnormalities, and in various studies, between 17 - 30% of patients with asthma develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Click the icon to see an image of sinusitis.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

About 10% of adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition and is associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Acetaminophen (Tylenol) has been the traditional alternative for relief of minor pain for patients who are aspirin-sensitive. Unfortunately, recent evidence has muddied these recommendations. Moreover, some asthmatic episodes have been linked to high consumption of acetaminophen among adults. And a study of children with asthma reported that those who took ibuprofen were less likely to be hospitalized for asthma than those taking acetaminophen. This is of particular concern, since acetaminophen is the pain reliever of choice in small children.

Asthma occurs primarily at night (nocturnal asthma) in as many as 75% of patients with the condition. Attacks often occur between 2 - 4 a.m. Factors that might play role in nocturnal asthma may include one or more of the following:

Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways
Delayed allergic responses from exposure to allergens during the day
The wearing off of inhaled medications toward the early morning
An increase in acid reflux (back up of stomach acid) that causes airways to narrow
Postnasal drip that occurs during sleep
Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night

Some experts believe that nocturnal asthma may actually be a unique form of asthma with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. This condition generally occurs in children and young adults, most often during intense exercise in cold dry air. Symptoms are generally most intense about 10 minutes after exercising and then gradually resolve.

EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long duration of airway activity, as allergic asthma does. (However, some people have both forms of asthma.) People who have only EIA do not appear to require long-term maintenance therapy. A study of military recruits with EIA also reported that the condition does not hinder a person's overall physical performance.

Medications. Cromolyn, a mild anti-inflammatory drug, or short-acting beta2-agonists have been the treatments of choice for preventing EIA. Newer approaches for people who work out regularly include pretreatment with long-acting beta2-agonists, such as salmeterol (Serevent) or the regular use of inhaled corticosteroids.

Hints for Reducing EIA. EIA occurs only after exercise and is more likely to occur with regular paced activities in cold, dry air. The following are some suggestions for reducing its impact:

Warm-up and cool-down periods are important.
Patients with EIA might do better with activities that involve short bursts of exercise (tennis, football) than with exercises involving long-duration regular pacing (cycling, soccer, and distance running).
Breathing through a scarf or through the nose helps warm up the airways.
Restricting dietary salt might help reduce EIA.

Click the icon to see an image of exercise-induced asthma.

Prognosis

Asthma is the third major cause of hospitalization in children under age 15. The condition can be very serious in children, particularly those younger than age 5, because their airways are very narrow.

The severity of asthma is graded as mild intermittent and mild, moderate, and severe persistent. A patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. According to one report, 30% of asthma deaths occur in patients with mild asthma.

Asthma is rarely fatal in children, with only 187 asthma deaths reported in 2002 in children under age 18. In fact, a 2006 study from the U.S. Centers for Disease Control and Prevention reported that asthma death rates for children have steadily declined since 1999. (During the same time, the number of doctor visits for asthma treatment more than doubled.) Even low mortality numbers are unacceptable, however, since asthma deaths are largely preventable.

Factors associated with an increased risk of death from asthma in children include:

Previous life-threatening episodes of asthma
Lack of adequate and ongoing health care. (Most likely the reason for the higher fatalities rates in minority children.)
Significant behavioral problems
Underestimating the severity of an acute attack poses the greatest threat. Unfortunately, one study of children found that nearly 40% of them were unaware of asthmatic symptoms when they occurred.

African American children have more than six times the death rate of Caucasians in the age groups of 4 years and younger and 15 - 24 years. Hispanic children also have a higher risk.

The following signs and symptoms may indicate a life-threatening situation:

As the chest labors to bring enough air into the lungs, breathing often becomes shallow.
Lacking sufficient oxygen, the skin becomes bluish.
The flesh around the ribs of the chest appears to be sucked in.
The patient may begin to lose consciousness.

Asthma often progresses very slowly to a serious condition or may develop to a fatal or near-fatal attack within a few minutes. It is very difficult to predict when an attack will become very serious. Early symptoms or lack thereof do not always reflect the ultimate severity of an attack. Some studies even suggest that people at high risk for fatal or near-fatal asthma attacks are those with poor awareness of their own reduced ability to breathe and who are slow in seeking help. Monitoring peak flow rates is, therefore, an important management component, since it provides a more accurate assessment of lung function than symptoms alone.

In a 2003 study, researchers followed people with asthma for longer than 30 years. About a third of children had outgrown their asthma in adulthood. In general, the more severe the childhood asthma, the greater the likelihood that it will persist. For example, only 23% of children who experienced wheezy bronchitis (wheezing during respiratory infections) suffered from frequent or persistent asthma in adulthood.

There is evidence that severe asthma can cause long-lasting damage and possibly permanent scarring in some patients. The risk for such injury is highest, however, when asthma strikes children in the first 3 - 5 years. There does not appear to be any significant risk for long-term lung damage for children who develop mild-to-moderate persistent asthma between ages 5 - 12. Children adapt well to living with asthma, and even with severe asthma they can function as well as healthy children in virtually all areas of life.

Studies are mixed over the effects of emotional disorders on the severity of asthma. One study indicated that parents of children with asthma may suffer greater psychological stress than their children. A 2000 study reported that mild-to-moderate asthma does not significantly affect the psychological well-being of most children ages 5 - 12. Teenagers and preteens may have particular difficulty coping with what they perceive as the social stigma of asthma. Parents and older children should not hesitate to seek help from support groups, doctors, friends, or family members. Support programs may help children to better manage their asthma and even reduce hospitalization.

Although there have been few studies on the effects of asthma on schooling, a 2000 study reported that nocturnal (nighttime) asthma affected school attendance and performance in children and work attendance in their parents.

Risk Factors

Asthma affects about 5 million American children between the ages of 5 - 14. Asthma has dramatically increased worldwide over the last few decades, in both developed and developing countries. From 1980 - 1994, asthma increased 160% in American children younger than 4 years and has also dramatically risen worldwide. Experts are puzzling over the cause of this phenomenon. Possible causes and risk factors that are suspects in the dramatic rise in asthma in children include:

Survival rates are now higher in low-birth-weight babies, who may be more susceptible to asthma.
Declining rates in nursing may be a contributor. Breast milk contains important anti-inflammatory substances, such as omega-3 fatty acids, which might protect against asthma.
Western dietary habits (which commonly include more fast foods and less fruits, vegetables, fiber, minerals, and other nutrients) may contribute to the development of childhood asthma.
Children are spending more time indoors watching television, playing video games, or using the computer and are, therefore, overexposed to indoor allergens.
The trend of making homes more energy-efficient may result in dust mites being trapped inside them.

Among younger children, asthma develops twice as frequently in boys as in girls, but after puberty it may be more common in girls.

Urban Life. Urban life is strongly associated with a higher risk. Although poverty plays a significant role, urban life has been associated with a higher risk for asthma in any income group and among both children and adults. In some urban areas, as many as 25% of children have asthma or show signs of wheezing. In fact, it may be greatly underdiagnosed in city children. A 1999 study reported that almost a third of children in inner-city kindergartens had asthma symptoms without a diagnosis of the disorder; 10% had actually been diagnosed with asthma, mainly because their symptoms were severe.

Ethnicity. Since 1980, asthma rates have risen the most dramatically among African American children, and they have significantly higher rates of asthma than Caucasian children. Hispanic children are also at higher risk. Both groups of minority children are more likely to have fatal asthma than Caucasian children.

Some studies indicate that the difference in risk exists simply because African Americans and other minority groups are more likely to live in urban areas. Poverty and lack of access to health care also play a role. However, Caucasian children who live in cities also face a high risk for asthma, and rural African American children do not.

Urban life and socioeconomic factors, however, may not fully explain the ethnic disparity.

Low Birth Weight. Infants of low birth weight are at higher risk for lung problems and asthma.

Winter Birth. Children born in the winter may have a greater risk for asthmatic allergies to cockroaches than children born at other times of the year.

Vitamin D. A 2006 study suggested a link between vitamin D intake during pregnancy and development of early childhood asthma. Pregnant women who had a higher intake of vitamin D were less likely to give birth to children who developed asthma.

Breast Feeding. Most studies on breastfeeding report some protection against wheezing and asthma in the first year of life. Breastfeeding has many other benefits for the child as well. The American Academy of Pediatrics recommends exclusively breastfeeding for the child's first 6 months of life.

Complications of Pregnancy. According to a 2000 study, complications of pregnancy, specifically those involving the mother's uterus (such as post-birth hemorrhage, pre-term contractions, insufficient placenta, and restricted growth of the uterus), are associated with an increased risk of childhood asthma. Another study reported that delivery procedures such as Cesarean section, the use of vacuum extraction or forceps also raised the risk of childhood asthma.

In both adults and children, the incidence of obesity and asthma has been increasing over recent years. Studies report a strong association between the two conditions. Some experts suggest that excess weight pressing on the lungs may trigger the hyperreactive response in the airways typical of asthma. Others believe that asthma leads to obesity by inhibiting physical activity, although several studies have found no difference in activity levels between people with or without asthma. Some studies suggest that many obese people may be misdiagnosed as having asthma when they are simply short of breath, possibly because of the increased effort required for breathing.

In any case, there is evidence that losing weight can relieve asthma symptoms. Some evidence also suggests that people who are overweight (body mass index greater than 25) have more difficulty getting their asthma under control. Weight loss in anyone who is obese and has asthma or shortness of breath reduces airway obstruction and improves lung function. [See In-Depth Report #53: Weight control and diet.].

Damp Homes. Studies suggest that children who live in damp homes have a much higher risk for asthma.

Mental Health. Research indicates that poor mental health of parents and children are significant predictors of more severe symptoms in childhood asthma. A 2000 study suggested that high stress levels can predict the onset and severity of asthma in children genetically at risk for the condition.

Symptoms

In children with asthmatic symptoms, it is important to first consider as a possible cause inhaled foreign objects such as peanuts; viral infections such as croup; and bacterial infections, which may be accompanied by high fever and progress rapidly. Any child who has frequent coughing or respiratory infections should be checked for asthma.

The classic symptoms of an asthma attack include:

Wheezing when breathing out is nearly always present during an attack. Usually the attack begins with wheezing and rapid breathing, and, as it becomes more severe, all breathing muscles become visibly active.
Shortness of breath (dyspnea). Shortness of breath is a major source of distress in patients with asthma, although severe dyspnea does not always reflect a serious attack or reduced lung function.
Coughing. In some people, the first symptom of asthma is a nonproductive cough.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
Neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate
Sweating
Chest pain occurs in about 75% of patients. It can be very severe, although its intensity is not necessarily related to the severity of the asthma attack itself.

The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation persists for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)

Diagnosis

The doctor will consider a diagnosis of asthma if a child has a history of periodic attacks of shortness of breath, coughing, and wheezing, perhaps accompanied by tightness in the chest. The parent should describe the pattern of symptoms and possible precipitating factors, including:

Whether symptoms are more frequent during the spring or fall (allergy seasons)
Whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack
Any family history of asthma or allergic disorders such as eczema, hives, or hay fever

A number of disorders may cause some or all of the symptoms of asthma. Panic disorder can coincide with asthma or be confused with it. Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

If symptoms and a patient's history are indicative of asthma, the doctor will usually perform tests known as pulmonary function tests to confirm the diagnosis and determine the severity of the disease.

Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the doctor will determine several values:

Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.
Peak expiratory flow rate (PEFR), commonly called the peak flow rate, which is the maximum flow rate that can be generated during a forced exhalation.
Forced expiratory volume (FEV1), the maximum volume of air expired in 1 second.

If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:

If measurements fall, the doctor typically asks the patient to inhale a bronchodilator. This drug is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, the drug has most likely cleared the airways, and a diagnosis of asthma is strongly suspected.
If measurement results fail to show airway obstruction, but asthma is still suspected, the doctor may perform a challenge test. It involves administering a specific drug (histamine or methacholine) that usually increases airway resistance only when asthma is present.

The patient may be given skin or blood allergy tests, particularly if a specific allergen is suspected and available for testing. Allergy skin tests may be the best predictive test for allergic asthma, although they are not recommended for people with year-round asthma.

One of the most common methods of allergy testing is the scratch test or skin prick test. The test involves placing a small amount of the suspected allergy-causing substance (allergen) on the skin (usually the forearm, upper arm, or the back), and then scratching or pricking the skin so that the allergen is introduced under the skin surface. The skin is observed closely for signs of a reaction, which usually includes swelling and redness of the site. With this test, several suspected allergens can be tested at the same time, and results are usually available within about 20 minutes.

Tests that either rule out other diseases or obtain more information about the causes of asthma include the following:

A complete blood count
Chest and sinus x-rays
Computed tomography (CT) scans. CT scans may be helpful in certain cases, such as for determining wall thickness in airways in patients who are difficult to treat, which could signify a higher risk for lung damage.
Examination of the patient's sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma).
Researchers are investigating measurements of certain chemicals in sputum or exhaled air that indicate airway inflammation. Such chemical markers include nitric oxide and hydrogen peroxide. For example, high levels of nitric oxide may prove to be a simple and noninvasive way of diagnosing asthma.

Treatment

Treating an Acute Attack in the Hospital. An acute attack may require hospitalization. Laboratory tests, an electrocardiogram (ECG), and a chest x-ray are performed to determine lung function, oxygen levels, and other indications of severity or rule out other causes. Depending on the results, the following treatments may be given:

Beta2-agonists are the standard therapy. They are typically administered with a nebulizer (a device that administers the drug in a fine spray). Studies suggest, however, that even very small children may be able to use metered-dose inhalers (MDIs), which are just as effective and more convenient than nebulizers. (Intravenous delivery is not recommended in most cases.)
An anticholinergic drug (ipratropium) is sometimes added to improve symptoms.
A corticosteroid (commonly called a steroid) given within the first hour helps reduce the need for hospitalization. Steroids may be administered intravenously, as a shot, or orally. Children may respond well to oral steroids.
Oxygen is usually administered, and can be life saving in severe cases.
Infusions of magnesium sulfate open airways and are an important emergency treatment for adults. Its benefits for children need to be further demonstrated.
In life-threatening situations, the patient may require mechanical ventilation.

Antibiotics are not useful for asthma attacks if there is no strong evidence of the presence of a bacterial infection. Viral infections, most often colds and the flu, are more likely to trigger an asthma attack. In such cases, antibiotics are not helpful and may have adverse effects.

Discharge and Relapse After Hospitalization. It typically takes about 3 - 4 hours to determine if a patient can be safely sent home or if they need to stay. Patients are generally discharged when:

Symptoms are gone or minimal, and
The peak expiratory flow rate is 70% or more of the predicted rate

Despite reasonable precautions, between 12 - 16% of patients relapse within 2 weeks of leaving the hospital. Receiving a steroid shot at discharge or taking an oral corticosteroid for a few days can reduce this risk.

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. In addition, good communication between the doctor and patient is a key factor in a successful management program.

Medications for asthma fall into two categories:

Rescue Medications. Medications that open the airways (bronchodilators, or inhalers) are used to quickly relieve any moderate or severe asthma attack. These drugs are usually short-acting beta-adrenergic agonists (beta2-agonists). Other drugs used in special cases include corticosteroids taken by mouth and anticholinergic drugs. None of these drugs have any effect on the disease process itself. They are only useful for treating symptoms.
Maintenance Medications. Simply coping with asthma symptoms without also controlling the damaging inflammatory response is a common and serious error. For adults and children over age 5 with moderate-to-severe persistent asthma, experts now recommend inhaled corticosteroids and long-acting beta2-agonists.

Parents can greatly reduce the frequency and severity of their children’s asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. Unfortunately, many patients do not understand the difference between medications that provide rapid, short-term relief and those that are used for long-term symptom control. Many patients with moderate or severe asthma overuse their short-term medications and underuse their corticosteroid medications. The overuse of bronchodilators can have serious consequences; not using steroids can lead to permanent lung damage.

Patients need to understand that asthma symptoms can change quickly over time and that treatment strategies may need to change in response. In 2005, the two leading U.S. allergy associations published joint guidelines on controlling asthma. The guidelines emphasize that asthma treatment decisions need to be made on an individual basis. It is important that patients have a close relationship with their doctor. The doctor needs to evaluate a patient’s asthma symptoms at each visit to determine any need for changes in medication. According to the guidelines, asthma management is classified as either “well-controlled” or “not well-controlled.” The doctor may need to change some medications, or increase or decrease the dosage, depending on whether a child’s asthma is well-controlled or not well-controlled.

These are the signs of well-controlled asthma:

Asthma symptoms occur twice a week or less
Rescue bronchodilator medication is used twice a week or less
Symptoms do not cause nighttime or early morning awakening
Symptoms do not limit work, school, or exercise activities
Peak flow meter readings are normal or the patient’s personal best
Both the doctor and the patient consider the asthma to be well controlled


Classification	Symptom Frequency	Children Age 5 Years and Younger: Recommended Treatment	Children Older Than 5 Years: Recommended Treatment
Mild intermittent	At least 2 days per week. At least 2 nights per month.	No daily medication.	No daily medication. If severe attacks occur, systemic corticosteroids recommended.
Mild Persistent	More than 2 days per week, but less than once per day. More than 2 nights per month.	Preferred treatment: Low-dose inhaled corticosteroids with nebulizer, or MDI with holding chamber with or without face mask. Alternative treatment: Cromolyn or leukotriene-antagonist.	Preferred treatment: Low-dose corticosteroids. Alternative treatment: Cromolyn, leukotriene modifier, nedocromil, OR sustained release theophylline.
Moderate Persistent	Daily daytime symptoms. More than 1 night per week.	Preferred treatment: Low-dose inhaled corticosteroids and long-acting beta2-agonists OR medium-dose inhaled corticosteroids. Alternative treatment: Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (especially if severe attacks occur): Medium-dose inhaled corticosteroids and long-acting beta2-agonists; medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline.	Preferred treatment: Low-to-medium dose inhaled corticosteroids and long-acting beta2-agonists. Alternative treatment: Low-to-medium dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline, or increased medium dose inhaled corticosteroids. If needed (especially if severe attacks occur): Increase dosage of medium-dose inhaled corticosteroids with add-on long-acting beta2-agonists. Alternatively, increase dosage of medium-dose inhaled corticosteroids plus either leukotriene receptor antagonist or theophylline.
Severe Persistent	Continual daytime symptoms. Frequent nighttime symptoms.	Preferred treatment: High-dose inhaled corticosteroids and long-acting beta2-agonists plus (if needed) oral corticosteroids.	Preferred treatment: High-dose inhaled corticosteroids combined with long-acting inhaled beta2-agonists. Add, if needed: Oral corticosteroids. Repeat attempts should be made to reduce use of systemic corticosteroid and maintain control with inhaled corticosteroid.
Adapted from National Asthma Education and Prevention Program (NAEPP) Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma – Update on Selected Topics 2002 (EPR-2 Update).

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Studies suggest that many children fail to use the devices properly, although newer devices are easier to use than others. The basic devices are the metered-dose inhaler (MDI), breath-actuated inhalers, dry powder inhalers, and nebulizers.

MDIs have used chlorofluorocarbons (CFCs) as their propellants. CFCs are damaging to the environment and are now being replaced with other propellants (hydrofluoroalkane) that are more environmentally safe, and do not chill the device as CFCs do. Devices that don't use any propellants are also now available.

Metered-Dose Inhaler. The standard device for administering any asthma medication is the metered-dose inhaler (MDI). This device, particularly when used with a spacer, allows precise doses to be delivered directly to the lungs. (The spacer is a tube that is attached to the inhaler. It serves as a holding chamber for the medication that is sprayed by the inhaler.) MDI-delivered drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation.

The spacer helps improve medication delivery by allowing the patient additional time to inhale. They vary, however, in their effectiveness. It should be noted that MDIs can continue to deliver propellant even after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Nebulizers (not MDIs) are typically used in very small children, both at home and in the emergency room. However, recent studies suggest spacers may be better than nebulizers for children and shorten the time spent in emergency rooms. Studies also indicate that with the use of a face mask and a spacer, the MDI works well even for infants in the emergency room and may prove to be useable at home.

Click the icon to see an illustrated series detailing a metered dose inhaler.

Breath-Actuated Inhalers. Breath-actuated rotary inhalers (Easi-Breathe and Autohaler) deliver the drug directly to the back of the throat as the user inhales. Their primary advantage over the MDI is their ease of use. They also do not use CFCs as propellants. In comparison studies, patients have been very successful with the breath-actuated inhalers. They are not recommended for children under 8 years old.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2-agonists or corticosteroids directly into the lungs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler, Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. In one study, for example, the Turbohaler was easier to use than the Diskhaler and so achieved better delivery.

Humidity or extreme temperatures can affect DPIs' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).

Dry-powder may cause tooth erosion. Children are advised to rinse their mouths out right after using these inhalers and to brush twice a day with a fluoride toothpaste.

Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.

Nebulizers. A nebulizer is a machine that delivers a fine spray of medication-containing liquid. Nebulizers are often used for children younger than 3 years and sometimes for older children who have difficulty using the MDI. It takes 5 - 10 minutes to administer medication using a nebulizer. Because the spray is less targeted than with the inhaler, it must deliver large amounts of the drug. This increases the risk for toxicity and severe side effects. Nebulizers should not be used by children who can manage an inhaler. Their use has been associated with a higher rate of hospitalizations and longer duration of symptoms than inhalers. A 2007 study also suggested that the misuse of home nebulizers may be an important factor in asthma deaths in children and young adults. If children must use an albuterol nebulizer, parents should be sure that it does not contain the preservative benzalkonium, which actually narrows the airways.

Click the icon to see an illustrated series detailing the use of a nebulizer.

Asthma triggers a vicious emotional-physical cycle:

Breathlessness and wheezing incite a fear of suffocation and death, even in very small children.
This anxiety produces further constriction on the muscles surrounding the airways, which makes breathing even more difficult.

Caregivers must first focus on alleviating their own anxiety, which can heighten a child's own fears. The next step is to help the child relax. One method for this is as follows:

The child sits comfortably, bending slight forward with the eyes closed.
The hands are placed gently over the navel.
The child is then told to pretend the stomach is a balloon.
The "balloon" must be "blown up" by inhalation, not exhalation. The child can tell if this working because the hands will move slightly apart.
When the child breathes out, the "balloon" will be made flat.

This exercise both relaxes the child and discourages shallow, oxygen-poor breathing. Massaging the child in gentle circles on the chest is relaxing and may also loosen mucus.

Other recommendations include:

A child may also find relief by lying stomach-down on several pillows so that the head is slightly lower than the chest while the caregiver gently pats the back between the shoulder blades.
Warm liquids, such as soup or hot cider, are effective in loosening mucus and may also relax bronchial muscles. Cold fluids, like cold air, should be avoided.
Overhydration (too much liquid) can be harmful, however, so these drinks should not be forced on the child.
Warm, moist air from vaporizers can greatly ease and moderate asthma attacks.
Daily massages and breathing and relaxation techniques to reduce stress can be very helpful.

Many adults self-manage their asthma using daily monitoring of peak air flow with adjustments of the medications as needed. This involves the use of a peak flow meter, which measures peak expiratory flow rate (PEFR).

Click the icon to see an image of a peak flow meter.

Studies suggest, however, that for most children with asthma, an educational program is just as effective for managing the condition as monitoring. Most children do not need to monitor their peak air flow on any regular basis.

Quick-Relief Medications

These medications quickly control acute asthma attacks.

Beta2-agonists do not reduce inflammation or airway responsiveness but serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. A short-acting inhaled beta2-agonist, taken as needed, is often the only medication used by children with chronic mild asthma.

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lungs to be restricted. When an asthma attack occurs, mucus production is increased, muscles of the bronchial tree become tight, and the lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound.

Specific short-acting beta2-agonists include:

Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in America. Other similar beta2-agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). Isoetharine (Bronkometer, Bronkosol) is available in nebulizers.
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard drugs. Xopenex is administered with a nebulizer, and studies have indicated that it is as effective as albuterol with fewer side effects. The original formulation of Xopenex was administered with a nebulizer. A new metered-dose inhaler formulation was launched at the end of 2005. It is approved for children age 4 years and older.

Short-acting bronchodilators are generally administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, a doctor may prescribe corticosteroids or other drugs to treat underlying inflammation.

Side Effects of Beta2-Agonists. Side effects of all beta2-agonists may include:

Anxiety
Tremor
Restlessness
Headache
Fast and irregular heartbeats. A doctor should be notified immediately if this side effect occurs.
These drugs should be taken with caution by children with diabetes or a history of seizures.
Beta2-agonists have serious interactions with certain drugs and parents should tell the doctor about any other medications their child is taking.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. Over time, some patients may become tolerant to many effects of short-acting beta2-agonists. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta2-agonists may increase the chances of a reduced effect from the short-acting forms.

A 2005 landmark study suggested that patients’ differing clinical response to albuterol may be based on their genotype. Albuterol targets the beta-adrenergic receptor. In the Beta-Adrenergic Response by Genotype (BARGE) trial, researchers studied the effects of albuterol on patients with two different forms of this receptor. The results suggested that patients with the arginine form of the receptor did not respond to albuterol. These patients’ asthma symptoms actually improved when albuterol was not used. By contrast, patients with the glycine form of the receptor had improved asthma control with albuterol.

Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. Ipratropium bromide alone is only modestly beneficial for acute asthma attacks. In fact, the drug is not approved specifically for asthma. Some parents report benefit for treating wheezing in infants. It is also sometimes used in the emergency room to treat children with severe asthma to enhance the effects of intravenous beta2-agonists.

Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively. A 2006 study indicated that oral prednisolone worked better than inhaled fluticasone for treating mild-to-moderate asthma attacks in children in emergency rooms. However, children often have difficulty taking these drugs because they have a bitter taste and can cause vomiting. Taking oral dexamethasone for 2 days may be as effective and more tolerable than the standard 5-day regimen of prednisone/prednisolone. Prolonged use of oral steroids has widespread and sometimes serious side effects, so they are not generally give to children for longer than a few days.

[See In-Depth Report #4: Asthma in adults.]

Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (they do not relax the airways) and have little effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. They can also help prevent asthma attacks from occurring. Many studies have shown that the use of inhaled corticosteroids in patients with moderate-to-severe asthma significantly reduces the rate of rehospitalizations and deaths from asthma.

Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (By contrast, oral steroids have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy under the following circumstances:

For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.

Examples of inhaled corticosteroids:

Inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer drugs are more powerful than the older generation of inhaled drugs. Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is the first such medication to be approved for children in this age group.
The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) was approved in 2005 for patients age 12 and older.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhalers that use very fine sprays (QVAR, Autohaler) to deliver the drugs deep into the lungs may prove to be as effective as the newer, more potent steroids.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are also available. These include Symbicort (budesonide/formoterol), which was approved in 2006 for patients ages 12 years and older.

Expert guidelines recommend inhaled corticosteroids as the preferred first-line therapy for children with mild-to-moderate asthma. Nevertheless, they are still significantly underprescribed in the patients who need them most. An important 2007 study of 6 - 14 year old children with asthma compared inhaled corticosteroid therapy (fluticasone) with an inhaled corticosteroid/long-term beta2 agonist (fluticasone/salmeterol) and a leukotrine receptor antagonist (montelukast). The results indicated that fluticasone alone worked better than the other two treatments.

Researchers have been investigating whether early treatment with corticosteroids can help prevent the development of asthma in at-risk children. Two important 2006 studies in the New England Journal of Medicine suggested that while inhaled corticosteroids helped ease symptoms and reduce breathing problems in pre-school children at risk for asthma, they did not help protect against asthma development.

For now, experts caution against corticosteroids for infants and toddlers with mild asthma and urge close monitoring especially for children under age 5 with severe asthma who are receiving high doses. Because the newer potent drugs, particularly fluticasone, may produce major side effects similar to oral steroids, it is important when treating all children to aim for the lowest effective dose possible. Fortunately, studies suggest that low doses of fluticasone may achieve the same benefits as with high ones, thus reducing risks for serious side effects. Better delivery methods may also allow lower doses.

Side effects of inhaled steroids may include:

The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but not common with inhalators.
Some children experience changes in mood, memory, and behavior. These changes are not permanent.
Some studies have suggested a higher risk for gum inflammation.
Oral steroids reduce bone density. Research reports that inhaled steroids -- both older and newer drugs -- may also affect bone growth and density. However, a number of studies report only a slight effect (about half an inch) on children's growth, which may be only temporary. It is still unknown if these drugs have any significant long-term effect on bone density. Calcium supplements may help prevent bone loss that is due to inhaled steroids.
It is not yet known whether inhaled steroids affect lung growth in very young children. Steroids administered using nebulizers are of particular concern.
There is also some concern that the stronger drugs, particularly fluticasone, suppress the adrenal system to a greater degree than other steroid inhalants. This effect, in turn, reduces levels of natural steroids -- notably cortisol, the major stress hormone. (This is a serious side effect of oral steroids).

Long-acting beta2-agonists are used in combination with inhaled corticosteroids for treating children with moderate-to-severe asthma. These drugs include include salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer). A single inhaler (Advair Diskus) that combines both salmeterol and the corticosteroid fluticasone is available for children age 4 years and older, and an inhaler (Symbicort) combining formoterol and the corticosteroid budesonide is approved for children age 12 years and older.

Long-acting beta2-agonists are used for preventing an asthma attack (not for treating attack symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so they are particularly effective during the night. These drugs also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

However, research indicates that long-acting beta2-agonists can worsen asthma by increasing symptom severity. These drugs may also increase the risk for asthma-related deaths. Experts are still trying to determine when long-acting beta2-agonists should be added to an asthma treatment plan. If a child’s symptoms do not improve or if symptoms worsen with this type of drug, the doctor will recommend discontinuing it. Patients should not, however, stop taking this drug or other asthma medications without first talking with their doctors.

Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting drugs.

Specific Warning on Salmeterol and Formoterol. In 2003 a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. Serevent and Advair are approved for patients age 12 years and older. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer, approved for patients 5 years and older). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. Long-acting beta2-agonists require up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. The FDA recommends that patients:

Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma.
Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing.
Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs.
Do not stop using any asthma medicines without first talking to your doctor.

Cromolyn sodium (Intal) is both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Cromolyn has been the anti-inflammatory drug of choice for prevention of asthma attacks in children over age 4 with chronic moderate asthma. It is not as effective as inhaled corticosteroids, however, for reducing hospitalization rates, improving symptoms, and reducing the use of beta2-agonists in children with persistent asthma. Still, cromolyn has a well-known long-term safety record, while the long-term adverse effects of corticosteroids in children are still not fully known. Many children who need asthma maintenance therapy will still do well on cromolyn. (It may not provide any real benefit for children under age 4.)

Nedocromil (Tilade) is similar to cromolyn and needs to be taken only once a day. It also prevents asthmatic reactions to cold and exercise. It is not used in very young children. A cromolyn nasal spray called Nasalcrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Patients should not use it for self-medication without the advice of a doctor.

Side Effects. Side effects of cromolyn include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. Nedocromil has an unpleasant taste, and some people have complained of nausea, headache, and spasms in the airways, but no serious side effects have been reported.

Leukotriene-antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving helpful for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID) -induced asthma. However, most studies to date have reported better success with inhaled corticosteroids than with the leukotriene-antagonists. A 2006 study of children with mild-to-moderate persistent asthma indicated that the corticosteroid fluticasone worked better than the leukotriene-antagonist montelukast in controlling symptoms. Nevertheless, some studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages 2 - 5), since they have trouble with inhaled steroids.

Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these drugs appear to be safe and well-tolerated.

Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. In fact, usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotriene-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.

Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.

Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) is a mild-to-moderate bronchodilator that has been used to treat childhood asthma for more than 30 years. It is useful for treating nocturnal asthma and may also have anti-inflammatory qualities even in low doses.

Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can therefore be taken once or twice a day with good results.

Side effects may include changes in behavior, mood, and memory. If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed but the following precautions should be noted:

Infants tend to metabolize the drug extremely slowly and, therefore, should receive very low doses.
By the time children reach age 1, however, they metabolize the drug faster than adults. There is a risk, therefore, of toxic effects.
Fever and certain antibiotics may slow down the rate at which theophylline is eliminated from the body. In such cases, the doctor may want to reduce the dosage of theophylline.

If a child is taking theophylline on an ongoing basis, the doctor should monitor the drug level at the start of therapy and at regular intervals thereafter.

Omalizumab (Xolair) is FDA-approved for patients age 12 and older who have moderate-to-severe persistent asthma related to allergies. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), a genetically developed drug designed to attack very specific targets. Omalizumab is administered by injection every 2 - 4 weeks. It is used only to treat patients whose symptoms are not controlled by inhaled corticosteroids.

Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown excellent benefits of the drug, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements.

However, about 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). In 2007 the FDA requested the manufacturers of omalizumab to put a “boxed warning” on the medicine’s label emphasizing the drug’s risk for anaphylaxis. The boxed warning notes that patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.

The FDA recommends that healthcare providers observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to administer it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

[See In-Depth Report #4: Asthma in adults.]

Other Treatments

Alternative therapies are widely used by children, adolescents, and adults with asthma. In one study, nearly half of asthma or allergy sufferers resorted to alternative treatments. To date, however, evidence does not support most alternative therapies, including high-dose vitamins, urine injections, homeopathic remedies, and most herbal remedies.

Relaxation and Stress-Reduction Techniques. Patients report benefits from many stress reduction and physical techniques, such as acupuncture, hypnosis, breathing relaxation techniques, the Alexander technique, massage therapy, and meditation practices. There have been very few well-conducted studies supporting their use, however.

Acupuncture, hypnosis, and biofeedback are alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Breathing Exercises. Some studies have suggested that breathing exercises or training may be helpful. A number of different methods are available. One example is the Buteyko breathing method, an experimental approach designed to increase levels of carbon dioxide in the body. To do this, patients are trained to reduce their volume of breath and to avoid hyperventilation (over-breathing). Some studies report that patients using this method reduce their use of medications and improve their quality of life. The system originated in Australia and is not yet widely available in the U.S.

Probiotics. Probiotics are beneficial bacteria that may possibly help protect against allergies and asthma. Antibiotic overuse and modern hygiene may specifically be reducing these helpful organisms. Look for probiotics in active yogurt cultures and in supplements, which are being studied for protection.

Herbal Remedies. Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort), is a traditional herbal remedy used for seasonal allergies and asthma. In a 2002 study, it was as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period. However, little research exists on its effect on asthma. Overall, there is scant evidence supporting the benefits of herbs and nutritional supplements for asthma control.

Managing Asthma

The more allergies a child has, the more severe the asthma. Making lifestyle changes to reduce allergy attacks and other triggers is extremely important.

House dust is a reservoir for pollen and dust mites. Some experts believe that reducing household allergens and pollutants in the home could reduce asthma in children by 40%.

Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particular Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. Vacuuming actually stirs up both mites and cat allergens. If possible, avoid carpets and rugs.

Click the icon to see an image of a HEPA air filter.

Bedding and Curtains. Many experts recommend reducing exposure to dust mites by enclosing mattresses and pillows in semipermeable coverings. (Vinyl mattress covers limit airflow and may also worsen, or even cause, asthma in children. Synthetic pillows may pose a significantly higher risk for severe asthma attacks in children than feather or no pillows.) However, several 2005 studies suggested that such covers do not prevent asthma or allergies. Replace curtains with shades or blinds, and wash bedding using the highest temperature setting.

Click the icon to see an image of dust mite prevention.

One study found that children sleeping in bottom bunk beds are significantly more likely to develop asthma than siblings occupying the upper bunks. Families with children who have asthma or allergies should avoid bunk beds or be sure that children with asthma sleep in the top bunk. Even with standard beds, it may be useful to have them sleep as high off the floor as possible.

Exterminating Pests (Cockroaches and Mice). Use professional exterminators to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice, and attempt to remove all dust, which might contain mouse urine and dander.

Reducing Humidity in the House. Although warm, moist air from vaporizers can greatly ease and moderate asthma attacks, living in a damp house is counterproductive. Dust mites thrive in humidity and damp houses increase the risk for mold, so on-going humidifiers can be unhelpful. If they are used, humidity levels should not exceed 40%, and humidifier should be cleaned daily with a vinegar solution.

Controlling Pets. People with asthma who already have pets and are not allergic to them probably have a low risk for developing such allergies later on. When children are exposed to more than one dog or cat during their first year, they have a much lower risk for allergies and asthma.

For children who have an existing allergy to pets, however, the pets should be given away or kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, are now available for both cats and dogs to remove allergens from skin and fur and are easier to administer than wet shampoos.

Many of the same substances trigger both allergies and asthma. Common allergens include pollen, dust mites, mold and pet dander. Other asthma triggers include irritants like smoke, pollution, fumes, cleaning chemicals, and sprays. Asthma symptoms can be substantially reduced by avoiding exposure to known allergens and respiratory irritants.

Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke are strongly urged to quit. Studies indicate that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. Even smoky cooking can worsen asthma.

Parental smoking has been shown to increase the airway responsiveness of infants as early as the first 2 - 10 weeks of life. This extends even to the fetus of pregnant women who smoke. Such mothers tend to have babies born at a low birth weight, which affects lung function and increases babies' risks for asthma.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Avoid scheduling camping and hiking trips during times of high pollen count (generally, May and June for grass pollen and mid-August to October for ragweed).
Patients should avoid strenuous activity when ozone levels are highest, which usually occur in early afternoon, particularly on hot hazy summer days. Levels are lowest in early morning and at dusk.
Asthma attacks are often higher during thunderstorms. Some evidence points to a build-up of ozone that accompanies such storms. Other evidence suggests that the changing airflow patterns bring a sudden downdraft of air containing concentrations of pollens, small particles and allergens.
Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass.
Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem.

Reducing Exposure to Air Pollution. Children breathe faster than adults, taking in more pollutants, and therefore are particularly susceptible to soot and other small particles in the air. A 2001 study found an association between higher rates of asthma and other health problems in children who were exposed to high levels of specific pollutants (particularly sulfur dioxide and nitrogen dioxide). Diesel fuel exhaust has also been associated with worsening asthma in children.

Some experts point out that asthma rates in North America have increased over recent years while the prevalence of many common air pollutants have declined. So pollution is unlikely to be a primary cause of asthma. Regardless of whether pollution is an important cause of asthma, evidence strongly suggests that it can affect existing asthma.

Patients with asthma and chronic allergic rhinitis may require daily medications. Patients with severe seasonal allergies may be advised to start medications a few weeks before the pollen season, and to continue it until the season is over.

Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, especially for children with poorly controlled asthma, so it is important that the doctor carefully evaluates the child’s asthma condition.

[See In-Depth Report #77: Allergic rhinitis.]

Weight Loss. Children who are both asthmatic and overweight may reduce asthma symptoms simply with weight loss.

Fruits, Vegetables, and Whole Grains. Healthy foods are important for lung function. Specific foods that may be important for healthy lungs contain antioxidants (deep green and yellow-orange fruits and vegetables), selenium (fish, red meat, grains, eggs, chicken, liver, garlic), plant chemicals called flavonoids (apples, onions), and magnesium (green leafy vegetables, nuts, whole grains, milk, and meats).

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (preferably DHA-EPA, the important compounds in fish oil) have anti-inflammatory effects. Some evidence suggests they may be helpful for people with asthma.

Caffeine. Caffeine has properties that are similar to the asthma drug theophylline. A major analysis of studies reported that caffeine improved lung function for up to 4 hours after consumption. Although tea and coffee are the major sources of caffeine, some sodas contain it and should be avoided when children have an asthma attack. (People who are going to have their lung function tested should avoid drinking coffee, tea, or other caffeinated beverages for at least 4 hours beforehand.)

Food Allergies. Although about 70% of people with asthma believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. If young children show signs of or test positive for food allergies, however, parents should be extra cautious in preventing exposure to any asthma trigger. Some doctors now counsel all children with asthma to avoid nuts entirely, and, of course, children who experience reactions to any foods should avoid them.

Chemicals that may pose some risk for an allergic reaction are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in foods, such as frozen potatoes and tuna). Contrary to what many believe, dairy products do not appear to worsen asthma symptoms in people who are not already allergic to them.

Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise may help control asthma and reduce hospitalization.

Encourage children with asthma to swim and play sports, such as baseball, that will present less difficulty for them. Intense activities lasting less than 2 minutes, such as sprinting or competitive swimming, may cause fewer problems than longer-lasting exercises.

Young people who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga practice, which uses both stretching, breathing, and meditation techniques, may have particular benefits. One study reported that two-thirds of patients who practiced yoga regularly were able to reduce or stop taking their asthma medications.

Patients should consult their doctors before starting any exercise program. Exercise-induced asthma is a limited condition that has specific recommendations.

People with asthma should try to minimize their risk for respiratory tract infections. Washing hands is a very simple but effective preventive measure.

Patients with asthma should ask their doctor about getting the influenza ("flu") vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is considered safe for patients with asthma 12 years of age or older. In one study, patients with asthma treated with zanamivir experienced fewer flu symptoms, and their lung function improved.

People with asthma have no higher rate of anxiety or depression than the general population. However, such emotions interact with the effects of asthma and its treatments in important ways:

Negative emotions can discourage compliance with medication and the ability to cope.
Poor control of asthma symptoms, in turn, increases the risk for negative emotions.
Stress and depression have been associated with more severe symptoms and even an increased risk of fatal asthma attacks.

Some evidence suggests that stress reduction techniques, a positive attitude, and relaxation techniques may be very helpful in the long-term management of asthma.

Resources

www.lungusa.org -- The American Lung Association
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.aaaai.org -- American Academy of Allergy, Asthma, and Immunology
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.asthma-carenet.org -- Childhood Asthma Research and Education Network
www.njc.org -- National Jewish Center for Immunology and Respiratory Medicine
www.aafa.org -- Asthma and Allergy Foundation of America
www.aanma.org -- Allergy and Asthma Network, Mothers of Asthmatics

References

Akinbami L; Centers for Disease Control and Prevention National Center forHealth Statistics. The state of childhood asthma, United States, 1980-2005. Adv Data. 2006 Dec 12;(381):1-24.

Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006 May 11;354(19):1998-2005.

Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000052.

Douwes J, van Strien R, Doekes G, Smit J, Kerkhof M, Gerritsen J, et al. Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol. 2006 May;117(5):1067-73.

Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006 May 11;354(19):1985-97.

Haland G, Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M, et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006 Oct 19;355(16):1682-9.

Marks GB, Mihrshahi S, Kemp AS, Tovey ER, Webb K, Almqvist C, et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol. 2006 Jul;118(1):53-61.

National Asthma Education and Prevention Program Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics -- 2002. Rockville, MD. National Heart, Lung, and Blood Institute, US Dept of Health and Human Services; 2003. NIH publications 02-5074.

O'Byrne PM, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, et al. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma. Chest. 2006 Jun;129(6):1478-85.

Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006 Jun 20;144(12):904-12.

Schuh S, Dick PT, Stephens D, Hartley M, Khaikin S, Rodrigues L, Coates AL. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics. 2006 Aug;118(2):644-50.

Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol. 2007 Jan;119(1):64-72.

Review Date:
3/26/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Asthma

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Prevention
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Asthma is a chronic disease that involves inflammation of the lungs. Airways swell and restrict airflow in and out of the lungs, making it hard to breathe. The word asthma comes from the Greek word for "panting." People with asthma pant and wheeze because of the restricted flow of air.

Normally, when you breathe in an irritant or are subjected to stressful activity such as exercise, your airways relax and open, allowing the lungs to get rid of irritants or take in more air. With asthma, muscles in the airways tighten, and the lining of the air passages swells.

About 20 million Americans have asthma, including 9 million children. In fact, asthma is the most common chronic childhood illness. About half of all cases develop before the age of 10, and many children with asthma also have allergies.

Asthma can either be allergic or non-allergic. In allergic asthma, an allergic reaction to an inhaled irritant -- pet dander, pollen, dust mites -- triggers an attack. The immune system gets involved, but instead of helping, it causes inflammation. This is the most common form of asthma.

Non-allergic asthma does not involve the immune system. Attacks can be triggered by stress, anxiety, cold air, smoke, or a virus. Some people experience symptoms only when they exercise, a condition known as exercise-induced asthma.

While there is no cure for asthma, it can be controlled.

Signs and Symptoms

Most people with asthma may go for periods of time without any symptoms, then experience an asthma attack. Some people experience chronic shortness of breath that gets worse during an attack. Asthma attacks can last minutes to days, and can become dangerous if the airflow becomes severely restricted.

Primary symptoms include:

Shortness of breath
Wheezing -- usually begins suddenly; may be worse at night or early in the morning; can be made worse by exposure to cold air, exercise, and heartburn; is relieved by using bronchodilators (drugs that open the airways; see Medications)
Chest tightness
Cough (dry or with sputum) -- in cough-variant asthma, this may be the only symptom

If you experience any of these symptoms, seek emergency treatment:

Extreme difficulty breathing or cessation of breathing
Bluish color to the lips and face (called cyanosis)
Severe anxiety
Rapid pulse
Profuse sweating
Decreased level of consciousness (such as drowsiness or confusion)

Causes

Asthma is most likely caused by a combination of several factors. Genes play a part; you’re more likely to develop asthma if others in your family have it. Among those who are susceptible, exposure to environmental factors such as allergens (substances that cause an allergic reaction) or infections may increase the likelihood of developing asthma.

Risk Factors

The following factors may increase the risk of developing asthma:

Having allergies
Family history of asthma or allergies
Exposure to secondhand smoke
Having upper respiratory infections as an infant
Living in a large city
Gender -- among younger children, asthma develops twice as often in boys as in girls, but after puberty it may be more common in girls
Obesity
Gastroesophageal reflux (heartburn)

Triggers

Childhood asthma in particular can be triggered by almost all of the same things that trigger allergies, such as:

Sensitivity to allergens such as dust, cockroach waste, pet dander, indoor and outdoor mold, pollen
Air pollutants, such as smoke, aerosols, perfumes, diesel particles, sulfur dioxide, high ozone levels, and fumes from paint, cleaning products, and gas stoves
Changes in the weather, especially in temperature (particularly cold) and humidity

Other triggers include:

Activities that affect breathing (exercising, laughing, crying, yelling)
Stress and anxiety

Diagnosis

The symptoms of asthma can mimic several other conditions, and your doctor will take a thorough history to rule out other diseases. You may also have lung function tests to measure, among other things, how much air your lungs can hold and how much air you exhale. Your doctor may use a spirometer to measure how much air you exhale and how quickly you get air out of your lungs. Other tests may include chest and sinus x-rays, blood tests, or allergy tests.

Asthma is classified as

Mild intermittent: Having mild symptoms up to 2 days a week and 2 nights a month
Mild persistent: Having symptoms more than 2 a week but not more than one time in a single day
Moderate persistent: Having symptoms once a day and more than one night per week
Severe persistent: Having symptoms throughout the day on most days and often at night.

Prevention

Although there is no way you can prevent asthma, you can take several steps to reduce the number and frequency of attacks:

Avoid allergens and irritants as much as possible. For example, to reduce exposure to dust mites, use special mattress and pillow covers that keep allergens out and remove carpets from bedrooms. Clean your house frequently.
Exercise. Even people with exercise-induced asthma can stay active, and exercise will benefit you by strengthening your lungs and helping you maintain a proper weight. Taking precautions when it’s cold outside -- such as wearing a face mask to warm the air that you’re breathing -- can help you avoid asthma symptoms. Talk to your doctor before starting an exercise regimen.
Pay attention to your breathing. Watch for signs of an oncoming attack, such as wheezing. Your doctor may give you a machine called a peak flow meter that can detect slight differences in your breathing before you even notice them and allow you to take medication immediately to ward off an attack.
Treat attacks quickly. The sooner you treat an attack, the less severe it will be, and the less medication you’ll need.

If you have allergies, a process known as allergy desensitization may decrease the number of asthma attacks and their intensity, and lower the amount of medication you need. Desensitization includes regular injections of the allergen (substance causing the allergic reaction), with each shot containing a slightly higher amount. Gradually your immune system becomes used to the allergen and no longer attacks it. Talk to your doctor about whether desensitization is right for you.

Treatment

Avoiding asthma attacks, reducing inflammation, and preventing lung damage are the primary goals of treatment. The more you know about your condition, the more you can work closely with your doctor to develop a treatment plan. Preventing exposure to allergens or irritants and taking medication as prescribed are important for the successful control of asthma. You may need emergency medications during an asthma attack, but monitoring your breathing taking your medications every day will help you control asthma over the long term.

Severe attacks may require hospitalization for oxygen and medications that are given intravenously (IV).

Lifestyle

If you smoke, quit.
Lose weight if you are overweight; excess weight may put pressure on the lungs and trigger an inflammatory response.
Monitor your condition every day using a peak flow meter (a portable device that helps measure how your lungs are working). Keep a diary of readings to show your doctor; together, you will establish your "personal best" reading. You should call your doctor if your peak flow reading falls below 80% of your personal best and go to the hospital if it falls below 50%.
Keep a journal that logs changes or attacks -- it may help determine triggers

Medications

Medications for asthma are prescribed for two different purposes: to stop an immediate attack, and to control inflammation and reduce lung damage over the long term.

Quick relief medications -- These drugs are called bronchodilators and help open the airways when you have an attack.

Short-acting beta-adrenergic agonists start working immediately. These drugs include:

Albuterol (Proventil)
Isoproterenol (Isuprel)
Metaproterenol (Aluprent)
Pirbuterol (Maxair)
Terbutaline (Brethine)
Levalbuterol (Xopenex)

Another drug that might be prescribed to help open your airway is ipratropium (Atrovent).

Sometimes, steroids are needed for an acute asthma attack. They can take longer to work (from a couple of hours to a few days) and include:

Prednisone
Prednisolone
Methylprednisolone
Hydrocortisone

Long-term control -- These drugs are usually taken every day.

Inhaled corticosteroids reduce inflammation have fewer side effects than oral corticosteroids. They include

Beclamethasone (Qvar)
Budesonide (Pulmicort)
Flunisolide (Aerobid)
Fluticasone (Flovent)
Triamcinolone (Azmacort)

A class of drugs called leukotreine modifiers help reduce the production of inflammatory chemicals called leukotreines that cause your airways to swell. They include:

Montelukast (Singulair)
Zafirlukast (Accolate)

Cromolyn (Intal), Nedocromil (Tilade) -- These medications, which are inhaled, can help prevent mild to moderate attacks and are used to treat exercise-induced asthma.

Theophylline (TheoDur) -- This medication helps open airways and prevent asthma symptoms, especially at night. Too much can cause serious side effects, so your doctor will monitor levels in your blood.

Nutrition and Dietary Supplements

Although asthma cannot be cured by any nutritional supplement, people who have a chronic illness such as asthma should eat well-balanced meals that include plenty of fruits and vegetables. Some studies have shown that people with asthma tend to have low levels of certain nutrients, but there is no evidence that taking supplements has any benefit. Rather, an overall healthy diet will ensure you get the nutrients you need and help your body deal with a long-term condition such as asthma.

Choline (3 g per day) -- Choline, a B vitamin, may help reduce the severity and frequency of asthma attacks, and allow people with asthma to use bronchodilators less often. Some evidence indicates that higher doses (3 g per day) may be most effective. More research is needed to say for sure whether choline helps.
Magnesium -- The suggestion of taking magnesium to treat asthma comes from the fact that people who have asthma often have low levels of magnesium, and from some (but not all) studies showing that intravenous (IV) magnesium can be effective as an emergency treatment for an asthma attack. However, studies that have looked at whether taking magnesium orally was beneficial have shown mixed results. More research is needed.
Omega-3 fatty acids -- The evidence for using omega-3 fatty acids (fish oil) to treat asthma is mixed. At least a few studies have found that fish oil supplements may improve inflammation and symptoms in children and adults with asthma. But the studies have only included a small number of people, and one study found that fish oil might make aspirin-induced asthma worse. Talk to your doctor about whether a high quality fish oil supplement makes sense for you.
Quercetin -- Quercetin, a kind of antioxidant called a flavonoid, inhibits the production and release of histamine and other allergic/inflammatory chemicals in the body. Histamine contributes to allergy symptoms such as a runny nose, watery eyes, and hives. Because of that, quercetin has been proposed as a treatment for asthma, but no human studies have examined whether it works or not.
Selenium -- Studies suggest that people with asthma tend to have low levels of selenium. In addition, a population-based study suggested that eating selenium-rich foods may reduce the risk of asthma. And in one small study of 24 people with asthma, those who received selenium supplements for 14 weeks had fewer symptoms than those who received placebo. However, a recent study indicated that people who took 200 mcg of selenium per day for about eight years were more likely to develop type 2 diabetes. Talk to your doctor before taking selenium supplements.
Vitamin C (1 g per day) -- One preliminary study suggested that children with asthma experienced significantly less wheezing when the ate a diet that was rich in fruits with vitamin C. Vitamin C does have anti-inflammatory and antioxidant properties, which may help you maintain good health overall. Other studies have indicated that taking a vitamin C supplement (1 g per day) may help keep airways open, but other studies have found no benefit.
Other -- Other supplements that may have benefit for asthma include:
- Coenzyme Q 10 (CoQ10) -- if you have asthma, you may have low levels of this antioxidant in your blood. It is not known, however, whether taking CoQ10 supplements will make any difference in your symptoms.
- Lycopene and beta-carotene -- preliminary data suggests that these two antioxidants, found in many fruits and vegetables, may help prevent exercise-induced asthma.
- Vitamin B6 -- may be needed if you are taking theophylline because this medication can lower blood levels of this nutrient.
- Potassium -- levels in the body also may be lowered if you take theophylline.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a health care practitioner.

Boswellia (Boswellia serrata, 3 mg three times per day) -- Boswellia (also known as Salai guggal), an herb commonly used in Ayurvedic medicine (a traditional Indian system of health care), has shown promise in treating asthma. In one double-blind, placebo-controlled study, people who took boswellia had fewer attacks and improved lung function. Boswellia may help leukotreine modifiers work better. However, more research is needed. People who take medication to lower their cholesterol, or people who take nonsteroidal anti-inflammatory drugs (NSAIDs) should talk to their doctor before taking boswellia.
Coleus forskohlii -- Coleus forskohlii is another herb used in Ayurvedic medicine to treat asthma. A few preliminary studies that used inhaled coleus powder seemed to relieve symptoms, but more research is needed to know for sure. People who have diabetes or thyroid conditions should not take coleus. If you take an anticoagulant (blood thinner), taking coleus may increase your risk of bleeding. Pregnant women should not take coleus.
Tylophora (Tylophora indica, 250 mg one to three times per day) -- Tylophora has also been used historically to treat asthma. Some modern scientific studies show that it can help reduce symptoms, but the studies were not the best quality. More research is needed. Tylophora may cause serious side effects at high doses, so talk to your doctor before taking it. Do not take tylophora if you are pregnant, have diabetes, high blood pressure, or congestive heart failure.
Pycnogenol (Pinus pinaster, 1 mg per pound of body weight, up to 200 mg) -- A 2002 review of studies on a standardized extract from French maritime pine bark, called pycnogenol, suggests that it may reduce symptoms and improve lung function in people with asthma. Do not use pycnogenol if you have diabetes or take medication for high blood pressure. Taking pycnogenol with an anticoagulant (blood thinner) -- including aspirin -- can increase your risk of bleeding; talk to your doctor first.
Saiboku-to -- A traditional Japanese herbal mixture called Saiboku-to has helped reduce symptoms and allowed study participants to reduce doses of corticosteroids in three preliminary trials. In test tubes, Saiboku-to has shown anti-inflammatory effects. Saiboku-to contains several herbs, including Asian ginseng (Panax ginseng), Chinese skullcap (Baikal scutellaria), licorice (Glycyrrhiza glabra), and ginger (Zingiber officinale). Talk to your healthcare provider before taking Saiboku-to as the herbs it contains can interact with other herbs and medications.

Acupuncture

Some preliminary studies indicate that acupuncture may help reduce symptoms for some people with asthma, but not all studies agree. It is important to note that acupuncture should be used in addition to, not as a replacement for, conventional medicine when treating asthma.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of asthma based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type-- your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

Arsenicum album -- for asthma that generally worsens between midnight and 2 am and is accompanied by restlessness, anxiety, chills, and thirst.
Ipecacuanha -- for those with asthma, particularly children, who have significant tightness in the chest, a chronic cough with lots of phlegm that may lead to vomiting, and worsening of symptoms in hot, humid weather.
Pulsatilla -- for asthma with yellow or greenish phlegm that gets worse in the evening, in warm, stuffy rooms, or after consuming rich, fatty foods; this remedy is most appropriate for adults or children who are tearful and clingy or sweet and affectionate.
Sambucus -- for asthma that awakens a person at night with a sensation of suffocation; symptoms worsen when the person is lying down .

Mind-Body Medicine

Because stress and anxiety can make asthma worse, incorporating stress management techniques into daily life may help reduce symptoms. These techniques do not directly treat asthma, however.

Hypnosis -- may be especially useful for children, who can readily learn the technique.
Yoga -- in addition to general relaxation and reduction of stress, several studies of people with asthma have suggested that lung function improve with the regular practice. Any benefits in breathing appear to be slight, however.
Journaling -- A study published in the New England Journal of Medicine documented the positive effect of daily journaling on people with asthma. Some theorize that journaling allows for the release of pent-up emotions and leads to overall stress reduction.

Other Considerations

Warnings and Precautions

Long-term treatment with theophylline for asthma may reduce blood levels of vitamin B6.

Prognosis and Complications

People with asthma can live normal, active lives. Because asthma is a chronic illness, it requires self-care and monitoring over the long term, as well as close contact with your doctor. Most people with asthma have occasional attacks separated by symptom-free periods. Paying attention to your mood, lowering the stress in your life, and having a good emotional support system will help you take good care of yourself.

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Review Date:
9/23/2007
Reviewed By:
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

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

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.

A.D.A.M. Copyright

adam.com

Vasectomy and vasovasostomy

FitSugar — Wed, 08 Oct 2008 17:35:49 -0700

In This Report

Highlights
Introduction
Considerations
Male Contraception
Surgery
Complications
Unexpected Pregnancy
Long-Term Complications
Reversal Surgery
Assisted Reproductive Techn...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Search Continues for the "Male Pill"

Research is progressing on a male contraceptive, but there have also been setbacks. The drug miglustat (Zavesca), which is used to treat a rare condition called Gaucher's disease, had shown success in animal studies but failed to work in a clinical trial, according to results published in 2007 in Human Reproduction. Researchers are now investigating an experimental drug, Adjudin (AF-2364), which disrupts sperm production.

Reversible Inhibition of Sperm Under Guidance

Reversible inhibition of sperm under guidance (RISUG) is one of the investigational male contraceptives furthest along in clinical trials. It is currently in phase III trials in India, but it is not yet known when or if clinical trials will be conducted in the United States. RISUG is a non-hormonal contraceptive method that uses an injectable polymer gel to stop sperm flow within the vas deferens.

No-Scalpel Vasectomy

The no-scalpel vasectomy is gaining in popularity as an alternative to standard vasectomy, but it requires a well-trained doctor to perform it. Performed correctly by an experienced doctor, no-scalpel vasectomy can result in shorter surgical time and less bleeding, infection, pain, and postoperative complications, according to a 2007 review published in the Cochrane Database. If you are considering a no-scalpel vasectomy, make sure that your doctor has performed at least 15 - 20 of these procedures.

Vasectomy Reversal

Vasectomy reversal may work better than assisted reproductive technologies (such as sperm retrieval) for men who have had a vasectomy but later decide to have children, according to research presented at the 2007 annual meeting of the American Urological Association.

Introduction

In the United States, vasectomy emerged as a popular method of permanent contraception during the 1960s. Within a decade, 750,000 men were undergoing vasectomies each year. Vasectomy rates markedly declined in the 1990s and have now plateaued at about 500,000 a year. Worldwide, an estimated 42 million couples use vasectomy as a method of birth control.

The procedure works by surgically interrupting the route that the sperm take from the testicles (where they are produced) to the penis. After vasectomy, the testicles still continue to generate sperm, but their movement is blocked at the site of the vasectomy. Eventually the sperm die, and the patient's body absorbs them. During sex, semen is produced in the same amount as before vasectomy, but this fluid does not contain sperm.

The testes are where sperm are manufactured in the scrotum. The epididymis is a tortuously coiled structure topping the testis, and it receives immature sperm from the testis and stores it several days. When ejaculation occurs, sperm is forcefully expelled from the tail of the epididymis into the deferent duct. Sperm then travels through the deferent duct through up the spermatic cord into the pelvic cavity, over the ureter to the prostate behind the bladder. Here, the vas deferens joins with the seminal vesicle to form the ejaculatory duct, which passes through the prostate and empties into the urethra. When ejaculation occurs, rhythmic muscle movements propel the sperm forward.

Click the icon to see an animation about vasectomy.

Vasectomy should not be confused with castration. It has no noticeable impact on a man's ability to perform sexually, or on his sensation of orgasm and pleasure. It does not affect the balance of male hormones, male sex characteristics, or sex drive. Testosterone continues to be produced in the testes and delivered into the bloodstream. Sperm form a very small portion of semen, so patients notice no difference in the amount of semen produced during orgasm.

The male reproductive tract performs three functions:

It enables a man to produce offspring.
It provides him with a supply of male hormones.
It enables him to experience sexual pleasure.

The Traveling Sperm. The sperm's journey through the male body -- from the testes (the testicles) to the final stage (the orgasm) -- is long and complex:

Sperm are produced in the testes at a rate of 50,000 an hour within tiny ducts called seminiferous tubules.
Sperm do not mature in the testes. They must first pass into the epididymis, a C-shaped storage chamber adjoining the testes composed of a 20-foot coiled tube. The sperms' journey through the epididymis takes about 2 - 3 weeks. They are held here until sexual activity forces them to move on.
When a man experiences sexual excitement, nerves stimulate the muscles in the epididymis to contract. This forces the sperm to pass into one of two rigid and wire-like muscular channels, called the vasa deferentia. (A single channel is called a vas deferens. It is the vas deferens that is cut during vasectomy.)
Muscle contractions in the vas deferens from sexual activity propel the sperm along past the seminal vesicles, which are clusters of tissue that contribute fluid, called seminal fluid, to the sperm. The vas deferens also collects fluid from the nearby prostate gland. This mixture of various fluids and sperm is the semen.
Each vas deferens then joins together to form the ejaculatory duct. This duct, which now contains the sperm-containing semen, passes down through the urethra. (The urethra is the same channel in the penis through which a man urinates. During orgasm, however, the prostate closes off the bladder so urine cannot enter the urethra.)
The semen is forced through the urethra during ejaculation, the final stage of orgasm when the sperm is literally thrown out of the penis.

Click the icon to see an image of sperm.

Considerations

Having a vasectomy is a serious decision. The surgery is intended to be permanent. The great majority of men who seek a vasectomy have been married for 10 years or more. Not all are good candidates, however. It is important that both the woman and the man completely agree that they no longer want to have children. They should also agree that permanent birth control is the right decision for them. Ideally, the couple should view the operation as a mutual commitment to an already successful marriage or relationship. Vasectomy generally is not a good idea if the couple's relationship is under great stress. It is not a cure for emotional or sexual problems between a man and woman.

After deciding that permanent birth control is the best solution, a couple still has the option of either vasectomy for the male or tubal ligation for the female.

Studies indicate that 5 -11% of men who have vasectomies regret the decision. In one study, 56% of men seeking treatment for fertility were hoping to reverse their vasectomies. Thirty years ago, this percentage was only 5%.

A reversal procedure called vasovasostomy is available, but it is a major operation that provides no guarantee of restored fertility. In a study of procedures performed between 1980 - 1996, vasectomy rates had leveled off but vasovasostomy rates had increased in men by nearly 70% in the most recent 5-year period compared to the earliest 5-year period.

Vasectomies may be right for:

Men in relationships in which both partners agree they have all the children they want and both do not want to use or are unable to use other methods of contraception
Men in relationships whose partners have health problems that make pregnancy unsafe
Men in relationships in which one or both have genetic disorders that they do not want to transmit

Vasectomies may not be right for:

Men in relationships in which one partner is unsure about his or her desire to have children in the future. (Couples in which the woman is working when they make the decision are at particular risk for regretting the decision later on.)
Men whose current relationships are unstable, going through a stressful phase, or are marked by substantial conflict
Men who are considering the operation just to please their partners
Men who are counting on having children later by storing sperm or by surgical reversal of the vasectomy
Young men, who still have many life changes ahead
Men who are single (including those divorced or separated) at the time of vasectomy
Men who are having the operation primarily for the sake of their partners and not wholly for their own reasons
Men or couples whose only motive is freedom from distraction imposed by other contraceptive methods during sexual activity

Vasectomy should not be undertaken in response to temporary stressful situations that might block the desire for children. Such conditions may include illness, temporary financial crisis, death in the family, or birth of a child. Couples should wait through such short-term stresses or seek counseling or psychotherapy to be sure that they are not making a decision they will later regret.

All Future Scenarios. Before deciding on a vasectomy, the couple should consider all future scenarios for their life together, such as the following examples:

If a couple already has children, how would they feel about a vasectomy if one of their children died?
If financial stress is triggering the decision for a vasectomy, would improved affluence increase their desire for children?
How would the man consider the vasectomy if his current relationship ended, either by divorce or the woman's death?

The word "sterilization" has a deep emotional connotation for many people. Even though a couple may rationally accept the idea of a vasectomy, it is extremely important for each partner to be as open as possible about any negative feelings they might associate with the procedure. Such feelings on the part of either partner can have devastating consequences on a relationship if they surface only after the procedure has been performed. Openness with each other is essential in order to make a decision that is clear of any hidden apprehensions. Neither partner should be too embarrassed to request counseling if the emotional aspects involved in making the decision are too difficult to solve between themselves.

What the man may be feeling:

A man may have a poor self image, including concerns for his own physical health or sexual ability. Such men are likely to have a difficult time adjusting psychologically to vasectomy.
A man may not actually really want the procedure but may not want to confront a partner he loves who wants him to have it.

What the woman may be feeling:

A woman might believe, incorrectly, that a vasectomy is emasculating, but she might not want to express this idea to her partner.
On the other hand, some women fear that vasectomy may make their partner more attractive and encourage outside affairs. (Research from the 1970s indicates that married men who have a vasectomy are no more likely to indulge in extramarital sex than fertile men.)

Storing frozen sperm in a sperm bank before vasectomy might enable men to have children later. Before the vasectomy, the man collects sperm, which are frozen and stored until he wants to have a child. In one study, 1.5% of men who had stored sperm later used it for conception and most were successful. Other studies have shown a lower success rate, however, and it is a very expensive process. Experts believe that a man who wants to bank sperm should probably reconsider his decision to have a vasectomy because such a concern may indicate doubts about giving up his ability to father a child.

Male Contraception

As many as 40% of couples seeking vasectomy have experienced a failure with their previous method of nonpermanent birth control. Such failures can occur from misplacement of a diaphragm, an incorrectly implanted intrauterine device (IUD), or noncompliance with an oral contraception regimen. Couples who are unsure about permanent sterility should still consider carefully all birth control options.

Withdrawal before ejaculation is a form of natural contraception, but it is extremely risky and most people find it unsatisfactory. If used on a regular basis, the average risk for pregnancy is 24%.

The only other form of male contraception currently available is the condom. However, the average rate of pregnancy for couples that rely only on condoms for protection is still 12%. In adolescents, the risk with condoms is even higher, 18%. Even for those who use a good-quality condom correctly, the annual risk for pregnancy is 3%.

The condom should be put on before intercourse when the penis is erect, long before ejaculation, since the male can discharge sufficient semen to cause pregnancy before ejaculation occurs. (Even after a vasectomy, men who are not in a monogamous relationship with an HIV-negative partner should always wear a condom during sex for protection against sexually transmitted diseases. Vasectomy is not protective.)

Click the icon to see an illustrated series detailing how to apply a condom.

Condom Materials.

Latex. Condoms made of latex rubber are the most common types. When they are contoured for better fit and contain a spermicide, they can provide fairly effective protection. Some people are allergic to latex, however, and in some cases the reaction can be very dangerous. The latex smell may also be unpleasant for some people.
Polyurethane. Polyurethane condoms (Avanti, eZ-on) are also available. At this point, they have good acceptance by couples but have a higher breakage rate (6 - 7.2%) compared to the latex condom (1.1 - 2%). Other synthetic materials are under investigation.
Animal Membranes. Condoms made from animal membrane can prevent pregnancy, but sexually transmitted infections can permeate them.
Lubricants. Lubricants can be used to prevent tearing. Petroleum-based products (such as Vaseline and baby oil) and vegetable oils should not be used because they can corrode the condom.

Spermicides. Some condoms come prelubricated with sperm-killing substances called spermicides. The standard active ingredient in spermicides in the U.S. is nonoxynol-9, which attacks the surface of the sperm cell. These spermicidal-coated condoms, however, are no longer recommended for a number of reasons. Side effects include irritation of the vagina or penis, particularly if used often or in large amounts. It can also promote yeast and urinary tract infections in women. Evidence now strongly suggests that nonoxynol-9 does not provide any additional protection against sexually-transmitted diseases. In fact, research indicates that it actually increases the risk for HIV in women, possibly by causing injury in the vaginal area. Spermicides are no longer recommended for use with male condoms.

Researchers are developing male hormonal contraceptives that reduce levels of sperm. Animal studies and clinical trials are progressing, and a "male pill" may become a reality in the not-so-distant future. Current trials are focusing on male hormonal contraceptives that combine testosterone (the primary male sex hormone) with progestin, a synthetic form of progesterone (one of the primary female sex hormones).

Testosterone suppresses levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH and FSH are hormones that stimulate ovulation in women and production of testosterone in men. Low levels of these hormones interfere with sperm production, but they do not completely stop it. For this reason, researchers are investigating combining testosterone with progestin. The addition of progestin further decreases LH and FSH levels, along with sperm counts. Researchers are also investigating combining testosterone with gonadotropin-releasing hormone (GnRH), another type of hormone that interferes with LH and FSH secretion.

Most of the male contraceptives currently in late-stage clinical trials deliver hormones through implant, injection, or both. The implant is surgically placed under the skin where it releases a steady stream of the hormone. The injection is given once every several months. Some of the investigational male hormonal contraceptives use a testosterone implant with progestin injections, while others use a progestin implant with testosterone injections. Forms taken by mouth are also being investigated. It generally takes around 3 - 4 months for the treatment to take effect, and for sperm production to be reduced. Research indicates that the male hormonal contraceptives are easily reversible. A 2006 study in the Lancet reported men regained their full fertility within 3 - 4 months after stopping hormonal treatment.

Side effects of male hormonal contraceptives include weight gain, acne, and changes in mood. These side effects are typical of hormone-based therapies.

Because of hormonal side effects, researchers are also investigating non-hormonal male contraceptives. Several initially promising drugs (such as miglustat) have performed well in animal studies, but have failed in human studies. Some non-hormonal research is now focusing on an experimental drug called Adjudin, which appears to work by disrupting sperm maturation in the testes. A 2006 animal study showed positive results, but it is still unknown if this drug will work in humans.

Researchers are investigating procedures that block sperm flow in the vas deferens using various drugs or materials that are reversible. One promising method is called Reversible Inhibition of Sperm Under Guidance (RISUG). RISUG is a non-hormonal contraceptive that uses a polymer gel. The gel is injected into the vas deferens, where it coats the vas deferens' inner walls and kills sperm. The gel can be injected through the skin through a needle or by using the no-scalpel vasectomy technique of making a tiny hole in the skin. The procedure takes around 10 - 15 minutes to perform, and men can resume sexual activity within a week.

The effects of RISUG are long-lasting. Studies indicate that a single injection can provide contraceptive effect for 10 years or more. It is also easily reversible. When a man wishes to discontinue the contraceptive, the gel is removed by flushing the vas deferens with a solvent. The major side effect so far has been a temporary swelling of the scrotum following the injection.

RISUG is mostly being investigated in human trials in India. American researchers are also interested in investigating RISUG, but animal studies need to be conducted first. It will be several years before any human trials are started in the U.S.

The intra vas device (IVD) is an investigational non-hormonal contraceptive that uses tiny silicone plugs to block sperm from traveling through the vas deferens. The plugs are surgically inserted into the vas using the no-scalpel vasectomy procedure. In 2006, the Food and Drug Administration granted approval to expand human trials of the IVD in several U.S. cities.

Unlike hormonal contraceptives, the IVD does not cause side effects like weight gain and acne. But researchers are still figuring out how to make this contraceptive method reversible.

Gossypol, a yellow pigment extracted from the roots, seeds, and stems of the cotton plant, has been used in China, Africa, and Brazil as a male contraceptive. Cotton root was also used as folk medicine in the American South to treat menstrual pain and to induce abortions. The chemical destroys the lining of tubules in the testicles where sperm are produced, thereby inhibiting their formation.

Gossypol does not appear to reduce sexual desire or frequency of intercourse. In about 20% of men, sperm production does not come back, so it should be considered as potentially permanent birth control. It also may not be effective in some men, since small numbers of sperm may survive. Researchers are investigating gossypol-derived compounds that may have less toxicity. No one should take any so-called natural gossypol product without consulting their doctors.

Surgery

Vasectomy is a minor operation that takes about 30 minutes and is usually performed in a doctor's office or a family planning clinic. If the operation is performed under local anesthesia, the cost ranges from about $500 - $1,000. Most insurance policies will cover vasectomies performed as a minor outpatient procedure, but will not cover vasectomies performed as major surgery in an operating room. If a Vasclip procedure is performed, there may be an additional cost of $400 - $500 for this device.

The Procedure.

To prevent increased risk of bleeding, patients should avoid taking aspirin or NSAIDs (Advil, Motrin) for 10 days prior to the procedure.
Before the operation, the patient's scrotum is shaved and cleaned.
A local anesthetic is injected into the scrotum. Patients should ask their doctor about applying an anesthetic cream (EMLA) before the injection to reduce its pain.
The surgeon makes a tiny incision on one side of the scrotum and locates one vas deferens. The vas deferens is isolated, drawn through the incision, and clamped at two sites close to each other.
The segment between the clamps (which should be more than 15 mm, or a little over 1/2 inch) is then removed.
The surgeon then seals off (ligates) the tube with surgical clips, sutures, or cauterization with an electric needle. Fascial interposition is an additional technique that may be used in combination with these methods to improve closure. With fascial interposition, the surgeon pulls the fibrous layer covering the vas (the fascia) over the cut end of the vas and sews it closed. This increases the barrier and further reduces residual sperm. Recent research suggests that fascial interposition combined with cauterization or ligation/excision is the best method for sealing off the vas.
The surgeon may choose to close off either one end of the vas (called an open-ended procedure) or both ends (closed-ended technique). In the open-ended procedure, the vas section connected to the testis is left open, and the one leading to the prostate is sealed. In the closed-ended approach, both are sealed. Many surgeons now prefer the open-ended version because it has lower complication and failure rates than the closed-ended method, and it results in fewer cases of chronic pain.
After closing off the tube, the vas deferens is gently placed back into the scrotum.
The procedure is then repeated on the other side.
After a short rest, usually about half an hour, the patient can leave the doctor's office or clinic. Arrangements should be made ahead of time for someone else to drive the patient home.

Click the icon to see an illustrated series detailing a vasectomy.

A method of vasectomy called no-scalpel vasectomy (NSV) that does not require the use of a scalpel was developed in China in 1974. NSV is now used in at least one-third of vasectomies.

The technique takes about 10 minutes and is performed in a doctor's office or a family planning clinic. The no-scalpel vasectomy differs from a conventional vasectomy in the method of accessing the vasa deferentia:

In NSV, the doctor feels for the vas deferens under the skin and holds them in place with a small ring clamp.
Instead of making two incisions, the doctor employs a sharp hemostat, a special instrument that makes one tiny puncture and then is used to gently stretch the opening until the vas deferens can be pulled through it. (The surgeon must rotate his wrist to pull the vas out -- called a supination maneuver -- which may be difficult to perform.)
The vas is then sealed off using the same methods (clips, sutures, cauterization using an electric needle, or some combination) as conventional vasectomy. As with standard vasectomy, the closures can be open- or closed-ended.
There is very little bleeding with the no-scalpel vasectomy. No stitches are needed to close the tiny opening, which heals quickly and leaves no scar.

When performed correctly, NSV works just as well as conventional vasectomy, takes less time, and (according to a 2007 review) causes less bleeding, infection, and pain. Current research indicates that NSV is the safest type of vasectomy procedure. NSV is difficult to perform, however, and most surgeons must do about 15 - 20 procedures in order to be proficient. NSV is becoming a popular alternative to standard vasectomy, but it is important to select a doctor who is experienced with this procedure.

A simpler method of NSV, called percutaneous vasectomy, is now being used. Recent research suggests that it works as well as standard NSV and is easier to perform. Percutaneous vasectomy uses the same instruments as no-scalpel vasectomy, but with a different surgical technique. The hemostat is used to first puncture the skin (instead of spearing the vas and lifting it out). The ringed clamp is then passed through the incision and used to enclose the section of the vas that is then pulled out for closure. This avoids the need for the difficult wrist maneuver in NSV.

Vasclip. The Vasclip is a recent alternative to standard vasectomy. This very small rice-sized plastic clip locks around the vas deferens and stops the flow of sperm. Some studies have reported fewer post-surgical complications than with standard vasectomy, including infection and swelling. It may be more easily reversible than a standard vasectomy.

Complications

Vasectomy is a low-risk procedure, and the complications, which occur in about 10% of patients, are usually easy to control. One study of no-scalpel vasectomy, for example, reported only 7 complications out of 4,255 procedures and they were mostly minor. Pain or soreness typically lingers for a few days after the procedure, but this is normal and usually does not require a return visit to the doctor. No deaths resulting from vasectomy have been reported in the United States.

Nearly all men recover completely in a few days. The following are some guidelines after the operation to help recovery:

The local anesthetic wears off about 1 - 2 hours after the procedure, and most patients then experience a dull ache in the testicles and groin. The doctor may prescribe a painkiller for the first few days, continuing with mild over-the-counter pain relievers if discomfort persists. Acetaminophen (Tylenol) with or without codeine is the primary choice for postoperative pain. Aspirin, ibuprofen (Advil, Medipren, Motrin, Nuprin), naproxen (Aleve), or other non-steroidal anti-inflammatory drugs (NSAIDs) can cause bleeding and should be avoided.
The patient should stay in bed on his back for at least one day and apply ice packs for 8 hours. The doctor may suggest that the patient wear an athletic supporter.
Some oozing of blood onto the gauze pads is normal during the first 2 days after the operation.
The patient should not perform any heavy physical labor for at least 2 days. Sports and heavy lifting may be resumed 2 - 3 weeks after surgery.
A semen analysis is done about 6 - 12 weeks after surgery to ensure that no live sperm remain in the semen. Many urologists recommend delaying a semen analysis until 2 months after a vasectomy or 12 ejaculations (whichever comes first). The semen is usually collected at home in a small jar and delivered to the doctor's office, where it is examined under a microscope. A second semen analysis is sometimes performed again about 4 months after the vasectomy, although many experts now believe that a second sample is unnecessary unless sperm found the first time were motile (still able to move). According to a 2006 study, 25% of men never bother to return for follow-up sperm testing. Without a follow-up test, men do not know whether the vasectomy was successful. Until test results verify that there are no sperm in the semen, men are at risk of fathering unwanted pregnancies.

All men experience some pain in the scrotum (the sac that contains the testes) after the operation. This pain generally disappears within two days, although the patient may feel sore for a few more days. In rare cases, pain can be persistent, which is known as post-vasectomy pain syndrome. The cause of this is unclear.

A few men may have an allergic reaction to the local anesthesia and develop itching and hives.

Frequently, blood may seep under the skin, so that the scrotum and penis appear to be bruised. If there is no dangerous swelling, this painless problem usually disappears without treatment within 1 - 2 weeks. If the patient bleeds excessively in the days after the operation and requires more than two or three gauze changes per day, he should call his doctor.

In 2 - 5% of cases, bleeding inside the scrotum can cause a painful swelling known as a hematoma. In these cases, the scrotum swells up shortly after vasectomy. The doctor should be called immediately.

Infections occur in 4 - 9% of men after vasectomy. The incision site may become infected, causing redness and swelling around the incision. Antibiotics, antimicrobial creams or ointments, or both, along with hot baths several times a day will usually clear the infection in a few days. There have been a few cases of infections in the lining of the heart (endocarditis) and severe gangrene of the scrotum, but they are extremely rare.

Unexpected Pregnancy

Pregnancy rates after a vasectomy are estimated to be very low, about 1 in 1,000. There are two main reasons for an unexpected pregnancy:

Residual sperm were still alive when the partners had unprotected sex. This is the most common reason for an unexpected pregnancy after a vasectomy. Men should make sure they have follow-up sperm analysis testing. They should also continue to use birth control until their doctor notifies them that the test results confirm sterility.
Failure of the procedure and recanalization. Failure in some cases is due to a technical error, but most often it is due to recanalization -- when the cut ends of the vas spontaneously reconnect. Success rates are best when an experienced surgeon performs the vasectomy.

Once the patient feels comfortable, he can resume sexual activity, usually in about a week. During ejaculation, the patient may experience some discomfort in the groin and testicles at first due to the contraction of the vas deferens. This almost always diminishes as the tissues heal.

However, after the operation there are always some active sperm left in the semen for several months so the risk for pregnancy persists. It is essential that the patient and his partner continue to use other methods of birth control until his sperm count is zero. The patient is considered sterile only when there are no live or moving (motile) sperm in his semen. It takes, on average, around 3 months or 20 ejaculations to clear the viable sperm from the reproductive system, but it may take some men as long as 6 months to become sterile.

About a third of men experience a recurrence or persistence of sperm that have no ability to move (immotile) 12 weeks after surgery and, in one study, about 7% had persistently immotile sperm. Immotile sperm, however, cannot swim up the vaginal canal and pose no danger for fertility. In rare cases, vasectomies have to be repeated because live sperm persisted in the semen. The risk for sperm surviving indefinitely is, however, very low.

The primary reason for vasectomy failure itself is recanalization-- when the cut ends of the vas deferens spontaneously reconnect. Recanalization in some cases may be due to sperm granulomas. These are tiny balls of debris that form from sperm, scar tissue, and white blood cells at the incision site. Cells lining the inside of the vas deferens grow through the scar tissue and form a new channel through which the sperm can now move. In general, surgeons can reduce the risk for recanalization by leaving a gap between the two cut ends.

This natural vasectomy reversal can occur after any vasectomy surgical procedure, but it is uncommon, with most studies reporting it occurring in less than 1% of cases. When recanalization does occur, sperm counts are almost always very low and pregnancies are still rare. Most cases of recanalization develop within several months after the operation. In very rare cases (about 0.6%), sperm have reappeared a year or even longer after vasectomy.

Long-Term Complications

Sperm Granulomas. After vasectomy, sperm often leak from the vasectomy site or from a rupture in the epididymis, the tightly coiled, thin tube that connects the testicle to the vas deferens. Sperm elicit a very strong response from the immune system, which views them as foreign substances and attacks them. Sperm leakage therefore provokes an inflammatory reaction. The body forms pockets to trap the sperm in scar tissue and inflammatory cells. Firm balls of tissue about 1/2 inch in diameter then form; these are known as sperm granulomas. They occur in about 60% of vasectomy patients.

Although they rarely cause serious problems, one study reported that sperm granulomas were troublesome in 15% of patients. In about 3 - 5% of cases, sperm granulomas obstruct the already blocked ends of the vas deferens and generate pressure build-up in the epididymis. This can cause a rupture from the pressure of the fluid. In such cases, the testicles may become enlarged and painful. A damaged epididymis can be repaired, but if the patient later wishes a reversal of the vasectomy, disruption of this tiny tube makes success much less likely.

Epididymitis. Epididymitis occurs when an inflammation at the site of the vasectomy causes swelling of the epididymis. This condition may occur within the first year and can be treated with heat and anti-inflammatory medications. It usually clears up within a week.

The male reproductive structures include the penis, the scrotum, the seminal vesicles and the prostate.

Positive Effects. Surveys indicate that about 90% of men are satisfied with vasectomy and that the feeling persists. One study reported even higher satisfaction in the partners, with more than 95% of wives reporting satisfaction with the procedure. Younger and older couples, with or without children, were all equally likely to have favorable reactions to vasectomies. Most men who have vasectomies feel relieved that the worry about pregnancy is over, and most couples respond well to their new-found contraceptive freedom.

Negative Effects. Some men go through a brief period of self-consciousness, wondering whether others notice some difference in their masculinity. About half of vasectomy patients keep their operations a secret. They may believe that vasectomy is tainted by the stigma of emasculation and that knowledge of it would degrade them in the eyes of their friends and family. For most men, this tentativeness passes quickly.

In a few men, however, problems of poor self-image persist and require counseling. Some may experience depressed and angry emotions. They may actually require a mourning period over the loss of their reproductive ability (similar to what some women go through during menopause). These negative feelings usually resolve over time as the patient moves on to the next stage of his life.

A small percentage of couples experience serious difficulties with the adjustment. Their emotional distress most often manifests itself in sexual dysfunction, such as impotence, premature ejaculation, or painful intercourse. In such cases, however, the vasectomy is probably the catalyst but not the cause of such extreme reactions. Studies have indicated that men who experience erectile dysfunction after vasectomy are more likely to have female partners who are unable to accept the operation.

Research indicates that up to a third of men have some pain in or around the testes that lasts longer than 3 months. In a study of 700,000 patients with vasectomies, up to 10% reported long-term chronic pain around the testicles. In one survey, 19% of subjects reported chronic pain that was simply a nuisance, and 12% reported more severe pain. Another study that followed men for an average of 19 months reported that 27% had some pain in the testicles, although, in the great majority, the pain was brief.

Causes of Chronic Pain. In many cases the source of the pain after vasectomy is not known, although some of the following conditions may be a source of pain:

Scarring from the surgery
Obstruction of part of the epididymis that causes swelling in another section
Pinched nerves
In about 1% of all vasectomies, the epididymis becomes so congested with dead sperm and fluid that the patient feels a dull ache in his testicles. This condition, called chronic orchialgia, usually disappears within 6 months.
Some doctors believe that granulomas may cause more chronic pain than generally believed. Others point out, however, that open-ended procedures, which increase the risk for granuloma production, result in less pain than closed-ended techniques that produce fewer granulomas.

Treatments for Chronic Pain. Surgery may be required if time or more conservative measures fail to relieve pain. Procedures may include:

Removal of the epididymis and surrounding tissue tends to be effective if the pain is in the scrotum (the sac that contains the testes) and if abnormalities in the epididymis can be observed using ultrasound.
A surgical procedure that blocks nerves in the sperm cord can bring relief in severe cases.
Surgery to reverse vasectomy (vasovasostomy) may relieve chronic pain. In one study, nearly 70% of men became pain free, although researchers were unable to discover any biologic differences after the procedure that might explain such relief.

Prostate Cancer. Prostate cancer is the second most common cause of cancer death among American men. About 30% of all American men will develop at least localized prostate cancer at some time in their lives. Long-term high-normal levels of testosterone may be associated with an increased risk for prostate cancer. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have been concerned that such men have a greater chance for developing the cancer.

Click the icon to see an image of prostate cancer.

A 2002 review indicated a 10% increase in risk for every 10 years after the procedure. The authors of the study reported, however, that such increased risk may not be caused by vasectomy since the association was small and could be due to bias. Most recent studies report no higher danger. A rigorous 2002 study from New Zealand, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation. Another 2002 study, in fact, reported a lower risk for prostate cancer in men who had had vasectomies.

It is possible that the higher rates reported in the early studies may simply be due to earlier prostate screening in men who have had vasectomies. One study reported that about 25% of doctors screened men with vasectomies earlier for prostate cancer than those without the operation.

An expert panel has recommended that vasectomy reversal is not warranted to prevent prostate cancer and that screening criteria for prostate cancer should be the same for men with and without vasectomies. Men with a family history of prostate cancer can discuss the risks and benefits of vasectomy with their doctors, although the weight of evidence to date indicates there is no link between vasectomy and prostate cancer.

Testicular Cancer. There have also been some concerns that vasectomy could increase the risk of testicular cancer. However, studies show there is no association between the two.

Vasectomy is known to provoke immune system changes.

Anti-sperm Antibodies. Sperm continue to be produced after vasectomy but are disposed of in the body. In some men the immune system mistakes these sperm as foreign proteins (antigens) and produces anti-sperm antibodies that are designed to target and interfere with sperm's motility (ability to move). Up to two thirds of vasectomized men develop such anti-sperm antibodies. Infections in the genital tract, such as orchitis or sexually transmitted diseases, increase the risk for anti-sperm antibodies. The anti-sperm response itself appears to be a problem only if a man wishes to reverse the vasectomy.

Heart Disease and Other Changes. Some researchers are concerned that changes in the immune system might cause damage in other parts of the body, including contributing to heart disease. However, a large 2002 follow-up study of men who had vasectomies found no increase in risk for heart disease, stroke, or peripheral artery disease, even after more than 20 years. Nor did researchers find any evidence of greater risk for hardening of the arteries (atherosclerosis) or inflammation, which play a role in cardiovascular disease.

Click the icon to see an image of atherosclerosis.

Some experts have voiced concern that vasectomy may increase the risk for the bone-thinning condition known as osteoporosis. However, evidence to date does not support an association.

Studies suggest that men younger than their mid-40s who have vasectomies have twice the risk for kidney stones as their peers who have not had vasectomies. The increased risk persists for up to 14 years after the operation. Kidney stones are not life threatening, but they can be extremely painful. Drinking plenty of fluids is the best way to prevent kidney stones.

Click the icon to see an image of kidney stones.

Reversal Surgery

Although men should consider vasectomy a permanent decision, vasovasostomy is a reversal procedure that may restore fertility in men who change their minds. Vasovasostomies are also effective in relieving chronic pain from vasectomies in the rare case that this occurs.

One Australian study suggested that although the rate of vasectomies has not changed over the past few decades, the desire for reversal surgery increased by over 70% in the late 1990s compared to the early 1980s. Men who had vasectomies in their 20s are more likely to seek reversal later on than older men. The main reasons for requesting a reversal are remarriage, the death of a child, or an improvement in finances. Reversal may also be performed to relieve post-vasectomy pain, which occurs in a small percentage of men. However, fewer than 10% of patients who request reversals do so because of physical or psychological problems following vasectomy.

Standard Procedure. Vasovasostomy reconnects the severed ends of the vas deferens to reestablish the flow of sperm. The procedure is difficult:

It involves sewing together the two tiny ends of both tubes, each with pinhead-sized openings.
If the vas deferens is blocked, the surgeon may try to connect the epididymis to an area in the vas deferens that bypasses the blockage.

Vasovasostomy can usually be done on an outpatient basis, and patients can usually return to work within 1 - 2 weeks. It is far more difficult and expensive than vasectomy itself, however, and is even costlier if the procedure involves connecting the vas to the epididymis, which takes about 3 hours. It should be noted that reversal surgery is usually not reimbursed by insurance companies, and that the results may not be known for some time.

Microscopic versus Magnification Techniques. The surgeon may view the surgical site using either magnification instruments (called macroscopic vasovasostomy) or microscopic techniques. Advanced microscopic techniques are proving to increase the chances of a reversal's success. Although macroscopic vasovasostomy has a slightly lower success rate, pregnancy rates can still be over 50%, and it is less expensive and has a shorter operating time than microscopic procedures. Still, a 2003 study suggested the microscopic approach is preferable for repeat vasovasostomies when the initial procedure failed.

Laser Techniques. Laser surgery is being investigated and may prove to require less surgical expertise, reduce operating time, and result in fewer complications. At this time, however, results vary widely.

An Australian study reported that the pregnancy rates in the late 1990s after reversal surgery were nearly four times higher than they were in the early 1980s. Pregnancy rates of over 50% are now being reported after vasovasostomy. One study indicated that when successful conception occurs, it does so at an average of 1 year after the surgery.

A successful reversal is more likely if the following conditions are present:

The section removed during vasectomy was not long.
The original procedure was performed on straight sections of the vas deferens.
The pieces joined during the vasovasostomy are of equal size.

The closer in time the vasovasostomy is to the original vasectomy, the better. In one large study, the pregnancy rates were 76% for those who had vasectomy less than 3 years before reversal surgery, but decreased to 30% for those men who had a vasectomy more than 15 years earlier. The decrease in rates as time goes by is probably due to an increase in the chance for obstruction of the epididymis and the development of anti-sperm antibodies. Success rates, according to some studies, are slightly better if the male partner does not change female partners after the procedure. Other studies suggest that it makes no difference if the man has a new female partner. The age of the woman is an important factor, and the chances of achieving pregnancy are best for women younger than age 35. Some research suggests that men who have a vasectomy reversal may have a greater rate of sperm chromosomal abnormalities than normal fertile men.

Even though tubes are re-opened and sperm is restored in as many as 85% of men who undergo vasovasostomy, pregnancy is not guaranteed. Several factors may play a role in the failure of reversal surgery.

Epididymis Obstruction. If the sperm count does not recover within a reasonable period after vasovasostomy, it is often due to blockage from scarring that has occurred in the epididymis. This sometimes can be corrected with a second procedure. The doctor may be able to detect obstruction before the vasovasostomy by pressing and manipulating (palpating) the epididymis. If any part seems swollen or larger than other parts, an obstruction is very likely to be present and the patient is likely to need a vasoepididymostomy, which creates a bypass around the obstruction.

Antisperm Antibodies. In many cases in which vasovasostomy fails, the reversal procedure reopens the tubes but fertility is impaired because of a process called autoimmunity. With this condition, important immune factors called antibodies attack the body's own cells, mistaking them for antigens (any foreign microinvader that the immune system perceives as a threat).

In the case of vasectomy, the autoantibodies attack the sperm, and so are called antisperm antibodies. Such antibodies develop when sperm continue to be produced after vasectomy, but, instead of being confined to the reproductive passages, they leak out into the body. Once out of their natural habitat, the immune system perceives them as foreign invaders and develops antibodies to attack them.

Antigens are large molecules (usually proteins) on the surface of cells, viruses, fungi, bacteria, and some non-living substances such as toxins, chemicals, drugs, and foreign particles. The immune system recognizes antigens and produces antibodies that destroy substances containing antigens.

The antisperm antibodies bind to specific parts of the sperm (the head or tail) and cause problems depending on the site of attachment. Sperm may stick together (agglutinate), fail to interact with the woman's cervix, or fail to penetrate the egg. Even after vasovasostomy, such antibodies often persist.

Oxidation. The immune factors that trigger the autoimmune process may have other harmful effects as well. In a process called oxidation, they can trigger the release of particles called free radicals, highly reactive oxygen molecules that, in excess, can do considerable damage to cells and genetic material. When high levels of free radicals persist after a vasectomy, they may, in theory at least, injure sperm DNA, contributing to infertility.

Repeat Vasovasostomy. If pregnancy fails, in some cases a repeat vasovasostomy may be effective. Success rates depend on several factors:

The doctor's skill
Complications from the original operation
Effects of anti-sperm antibodies
Time elapsed since vasectomy (the shorter the better)
History of previous children. In one study, conception rates after reoperations were highest (80%) in couples who had had previous children. The pregnancy rate was only 17% when men had remarried.

A 2003 study indicated that the microscopic approach may be preferable for many repeat vasovasostomies.

Vasoepididymostomy. Vasoepididymostomy is a microsurgical technique that is useful when a vasovasostomy has failed because of damage to the epididymis. This procedure creates a bypass around the obstruction. It may be done on one or both sides of the testes.

To appreciate the difficulty of this operation, one should realize that the epididymis is 1/300th of an inch wide with a wall thickness of 1/1000th of an inch. Microscopic techniques are critical for the success of this procedure and require a surgeon who specializes in them. Refinements in vasoepididymostomy techniques are showing promising results, opening tubes in 77 - 85% of cases.

Success rates are higher for repairing obstructions closer to the testicles, because the epididymis is wider in this area. In general, pregnancy rates are around 25%, but higher rates have been reported. In one study of men who had vasectomy reversal more than 15 years after the original procedure, 62% required vasoepididymostomy, and the overall pregnancy rate was 43%. Pregnancy rates ranged from 49% in those who had had their vasectomy 15 - 19 years earlier to 25% in those who had the surgery 25 or more years before, with the highest rates occurring, not surprisingly, in those with the youngest wives.

Damage in other ducts and small tubes are a major reason for vasoepididymostomy failure. Ultrasound before the operation may be valuable to determine if these abnormalities exist, which would make it unlikely that the procedure would be successful.

If an initial vasoepididymostomy fails but conditions are favorable, a repeat procedure may still succeed.

If the patient did not contribute sperm for freezing and banking before vasectomy, some doctors suggest freezing sperm obtained during vasovasostomy as insurance against failure. Such sperm can be used in assisted reproductive methods later on if natural intercourse fails to achieve pregnancy.

There is some controversy, however, surrounding routine use of frozen sperm before a vasovasostomy. One study reported that so many sperm were non-motile at the time of the reversal surgery that freezing sperm obtained during the procedure provided little benefit. Nevertheless, new fertilization techniques are using even non-motile sperm with some success. Studies report successful pregnancies with frozen sperm. Some experts recommend routine sperm retrieval only for men undergoing bilateral vasovasostomy (those performed on both sides) and possibly for men who are having vasovasostomy with vasoepididymostomy. Men should discuss these options with their doctor.

Even though newer techniques such as intracytoplasmic sperm injection (ICSI) are improving pregnancy rates after vasectomy, vasovasostomy is still a better choice than assisted reproductive technologies (ART) for most men who want children.

Success rates with reversal surgeries are improving, and the costs are lower than with ART. In addition, a vasovasostomy does not pose a risk for multiple births. In one study, the pregnancy rate for vasovasostomy was 52%, whereas success after intracytoplasmic sperm injection (ICSI) was between 25 - 30%. (ICSI is the ART treatment of choice for men who have had vasectomy.) Even for men who have failed vasovasostomy, a repeat procedure appears to be less expensive than embarking on fertility treatments at that time.

ART may, however, be a better approach than reversal for men with evidence of anti-sperm autoantibodies due to vasectomy. ICSI may also be more effective than reversal surgeries in men whose vasectomy was conducted at least 15 years earlier.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) are available for men who want to conceive children after a vasectomy. The shorter the period since the vasectomy the better the chances of success. In one study, success rates after ART were highest (34%) when it was performed within 10 years of the vasectomy and lowest (8%) when ART occurred more than 20 years after vasectomy. Of course, the couples would be older as the duration between procedures increased, so pregnancy rates would be lower in any case. However, time elapsed after vasectomy appears to have an effect independent of a couple's age. Debate is ongoing about its advantages versus reversal surgeries for men who have had vasectomies and want children. Research presented at the 2007 American Urological Association annual meeting suggested that vasectomy reversal may work better than sperm retrieval or other ART.

The best assisted reproductive technology procedure for men who have had vasectomies or failed reversal surgery is intracytoplasmic sperm injection (ICSI). In this procedure, sperm are taken from the epididymis or testes using needles or microsurgical techniques.

The procedure itself injects a single sperm into an egg with the aid of powerful microscopic and robotic instruments. The fertilized egg is then implanted in the woman. [See In-Depth Report #67: Infertility in men.]

If a reversal surgery is not successful, a doctor may be able to retrieve sperm from the testes or the epididymis for use in assisted reproductive technologies (ART). Various techniques are now available for retrieval. The procedure may be done under local or general anesthesia, using a spring-loaded biopsy device, a thin needle, incisions, or microsurgical techniques. Rigorous trials on the best technique are lacking, although all can be successful. The choice will depend on the experience of the clinic and any underlying problems.

Testicular Fine Needle Aspiration. Testicular fine needle aspiration (TFNA) employs a fine needle to remove sperm. This can be performed with local anesthetic and by surgeons who do not have to be experienced in microsurgeries.

Microsurgical Epididymal Sperm Aspiration. Microsurgical epididymal sperm aspiration (MESA) uses microsurgical techniques to collect sperm that are close to blocked portions of the epididymis. It involves an open incision and may be done under general or spinal anesthesia in a hospital setting, although the patient can often go home the same day. The doctor accesses the epididymis and retrieves sperm with an extremely fine needle-like device. It has the advantage that it can retrieve the largest number of sperm compared to other procedures. However, as with any invasive procedure, it carries some risk of complications, such as bleeding or infection.

Percutaneous Epididymal Sperm Aspiration. Percutaneous epididymal sperm aspiration (PESA( uses a needle to obtain mature sperm from areas in the upper parts of the epididymis (the coiled tube where sperm are stored before ejaculation). It is done under local anesthesia, sometimes in the doctor's office, is less expensive than other techniques, and recovery is fairly painless. However, it has less of a chance of achieving sufficient sperm than MESA, and there is also a chance of hitting a blood vessel, causing bleeding.

Testicular Sperm Extraction. Testicular sperm extraction (TESE) is a microsurgery that removes a small amount of tissue from one or more areas of the testes using incisions and microsurgery techniques. The tissue is placed in a culture and chopped into tiny pieces. Sperm are liberated from the tiny tubes and extracted. It is a complex process, however. This is the second best method for men with vasectomies, according to some experts. It is more painful than PESA, however. In addition, if the procedure is repeated too often it can cause permanent alterations in testicular function that may reduce male hormone levels.

Testicular Sperm Aspiration. Testicular sperm aspiration (TESA) uses a needle-like biopsy device to draw a small sample of testicular tissue. Multiple attempts are sometimes required to retrieve sperm, and it is not as effective or as safe as TESE, although imaging techniques using ultrasound may improve results.

Resources

www.engenderhealth.org -- EngenderHealth
www.nichd.nih.gov -- National Institute of Child Health and Human Development
www.plannedparenthood.org -- Planned Parenthood
www.fhi.org -- Family Health International
www.auanet.org -- American Urological Association
www.urologyhealth.org -- Urology Health
www.newmalecontraception.org -- Male Contraception Information Center
www.imccoalition.org -- International Male Contraception Information Coalition
www.vasectomy.com -- Information on vasectomy

References

Amory JK, Muller CH, Page ST, Leifke E, Pagel ER, Bhandari A, et al. Miglustat has no apparent effect on spermatogenesis in normal men. Hum Reprod. 2007 Mar;22(3):702-7. Epub 2006 Oct 25.

Cook LA, Pun A, van Vliet H, Gallo MF, Lopez LM. Scalpel versus no-scalpel incision for vasectomy. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004112.

Mruk DD, Wong CH, Silvestrini B, Cheng CY. A male contraceptive targeting germ cell adhesion. Nat Med. 2006 Nov;12(11):1323-8. Epub 2006 Oct 29.

Review Date:
10/17/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Viral encephalitis

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Prognosis
Diagnosis
Treatment
Vaccinations
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

West Nile Virus

In 2007, 3,510 cases of West Nile virus were reported to the U.S. Centers for Disease Control. States with the highest number of reported cases included Colorado, California, and North Dakota. Of the reported cases, two-thirds were in the form of West Nile fever, and one-third were diagnosed as West Nile neuroinvasive disease (encephalitis and meningitis). However, the high proportion of neuroinvasive disease cases is due to the fact that serious cases of West Nile virus are more likely to be reported to health authorities than mild cases. In general, less than 1% of people who become infected with West Nile virus develop encephalitis.

West Nile Virus Symptoms and Diagnosis

Most people (80%) who are infected with West Nile virus do not have any symptoms. About 20% of people develop mild symptoms that include fever, headache, body aches, and nausea and vomiting. These symptoms can last from a few days to a few weeks. For the minority of people who develop neuroinvasive disease, symptoms can include high fever, headache, neck stiffness, muscle weakness, and convulsions. While West Nile neuroinvasive disease is rare, its neurological complications such as paralysis can be permanent.

Prevention

West Nile virus is carried by mosquitoes and is most common during the summer and early fall. The best way to prevent becoming infected with West Nile virus is to avoid being bitten by a mosquito. Use insect repellant when you go outside, especially during the peak mosquito hours of dusk and dawn. Remove mosquito-breeding environments (such as standing water in flower pots) from your property. Scientists are testing several different vaccines to protect against West Nile virus, but it will be many years before they are commercially available.

Introduction

Encephalitis is a rare but potentially life-threatening inflammation of the brain that can occur in people of all ages. The most common cause of encephalitis is infection by a virus. In very rare cases, encephalitis can also be caused by bacterial infection, parasites, or complications from other infectious diseases. This report focuses on viral encephalitis.

Many viruses can cause encephalitis. The West Nile virus, for example, has been responsible for high-profile outbreaks in the U.S. Most people exposed to encephalitis-causing viruses have no symptoms. Others may experience a mild flu-like illness, but do not develop full-blown encephalitis.

In severe cases, the infection can have devastating effects, including:

Swelling of the brain (cerebral edema)
Bleeding within the brain (intercerebral hemorrhage)
Nerve damage

The damage may cause long-term cognitive or physical problems, depending on the specific areas of the brain affected.

Other Viral Infections of the Central Nervous System. Viral infection and inflammation can affect multiple areas of the central nervous system, and is categorized by its location:

Meningitis: infection of the meninges (the membranes that surround the brain and spinal cord)
Meningoencephalitis: infection of both the brain and meninges
Encephalomyelitis: infection of the brain and spinal cord

Encephalitis caused by viruses in the United States generally fall into the following groups:

Arboviruses are the primary cause of acute encephalitis (sudden-onset encephalitis caused by direct infection). Arboviruses, short for "arthropod-borne viruses," are spread by mosquitoes and ticks.
Enteroviruses, such as coxsackievirus.
Herpes viruses are the other major cause of encephalitis in the U.S. This virus family includes herpes simplex, Epstein-Barr, cytomegalovirus, and varicella-zoster.
In rare cases, secondary encephalitis can develop following childhood viral diseases such as measles, mumps, and rubella.

[For more information, see the Causes section in this report.]

Encephalitis can develop shortly after an initial viral infection, or it can develop when a virus that was lying dormant in the body suddenly reactivates. Viruses are simple, but powerful infectious organisms.

The virus infects a person (host) by penetrating a cell membrane and ejecting its genetic material (its DNA or RNA) into the cell.
The viral DNA or RNA takes control of important cell processes, telling the cell to make more viruses.
The cell ruptures, releasing new viral particles that infect other cells.

There are two ways that viruses can infect brain cells:

The virus silently invades the body. There are no initial symptoms. The virus is carried by the bloodstream to the nerve cells of the brain, where they gather and multiply. Viruses that enter the brain in this manner are often widely scattered throughout the brain. This is called diffuse encephalitis.
A virus first infects other tissue and then invades brain cells. Viruses that are transmitted from other tissues usually cause focal infection, meaning they produce extensive damage in only a small area of the brain.

The brain and spinal cord comprise the central nervous system. The adult human brain weighs about 3 pounds (1.4 kilograms). There are two major parts of the brain:

The higher and larger forebrain (the cerebrum)
The lower and smaller brain stem

The cerebrum is the uppermost and largest part of the brain. It is the most highly developed section of the brain. There cerebrum has several components:

The Cerebral Cortex. The cortex is the outermost layer of the cerebrum. It is made of gray and white matter:

Gray matter is a thin sheet of nerve cells that cover the surface of the brain.
White matter is a bundle of insulated nerve fibers that underlies the cortex and makes up the core of the cerebral hemispheres.

The Hemispheres. The two hemispheres control higher brain functions, such as memory, learning, decision making, and processing input from the senses. They are each divided into four lobes, which regulate different brain functions:

Frontal lobe: This is the brain's "gatekeeper." It controls higher motor functions, including speech, and governs concentration, attention, inhibition, judgment, and personality traits.
Parietal lobe: Processes information from the senses and controls walking, posture, and head and eye movements.
Occipital lobe: Responsible for interpreting visual input from the eyes.
Temporal lobe: Responsible for interpreting auditory input from the ears. Also regulates how language is interpreted and retrieves information for memory storage.

The Basal Ganglia. The basal ganglia are clusters of gray matter within each of the lobes. They are important for coordinating voluntary muscle movement, balance, and posture.

The Limbic System. The limbic system is located deep in the cerebrum and controls interpretation of smell, instinctive behavior, emotions, and drives.

The brain stem is responsible for all vital functions. It is divided into the following areas, which are responsible for specific functions:

Medulla: sleep, breathing, heartbeat, digestion, activation of higher forebrain functions
Pons: sleep, breathing, motor control, activation of higher forebrain functions
Cerebellum: movement coordination
Midbrain: walking, posture, head, eye movement
Hypothalamus: body temperature, appetite, sexual behavior, reproductive hormones
Thalamus: communication with higher forebrain

The spinal cord extends out of the base of the skull through the vertebrae of the spinal column. It is continuous with the brain. Thirty-one pairs of nerves extend from the sides of the spinal cord to other parts of the body (the peripheral nervous system).

The meninges are three membranes that enclose the brain and spinal cord. They contain cerebrospinal fluid, which protects the central nervous system from pressure and injury.

Causes

Arboviruses

Arboviruses, including the West Nile virus, are transmitted by blood-sucking insects such as mosquitoes and ticks. Most of the time, the viral infections initially develop in birds. Insects that feed on the infected blood from a diseased bird (or reservoir ) carry the virus, and transmit it when they bite a susceptible host (such as an animal or a human). Because these insects play a role in the disease-transmission process, they are referred to as vectors.

Arboviruses multiply in blood-sucking vectors, nearly always mosquitoes. There is no evidence that these infections can be transmitted casually from one infected person or animal directly to another uninfected person without passing through a mosquito (or tick) first. (Although, a small number of West Nile virus cases have occurred through blood transfusions, organ transplantation, and possibly breast-feeding.) It should be stressed that only about 10% of people who are infected by an arbovirus develop encephalitis and that only about 1% of those infected show symptoms.

Arboviruses that cause encephalitis are primarily found in three virus families: Togaviridae, Bunyaviridae, and Flaviviridae. In the United States, the main mosquito-borne encephalitis strains are: Eastern equine, Western equine, St. Louis, La Crosse, and West Nile. Equine encephalitis causes disease in both humans and, as its name implies, horses. Powassan encephalitis is a less common tick-borne flavivirus that occurs primarily in the northern United States. Japanese encephalitis is the most common form of viral encephalitis to occur outside of the United States. It is endemic in rural areas in east, south, and southwest Asia, especially China and Korea. Venezuelan equine encephalitis is found in South and Central America.

Different arboviruses cause different forms of encephalitis. Although the overall disease is the same, there are subtle differences in symptoms and the type of brain damage they produce.


Eastern Equine Encephalitis
Virus Family	Togaviridae (genus Alphavirus)
U.S. Geographic Areas	Atlantic and Gulf coasts, in New England, and around the Great Lakes. States most affected are Florida, Georgia, Massachusetts, and New Jersey.
Symptom Onset	Symptoms appear 4 - 10 days following infection and can range from mild flu-like symptoms to full-blown encephalitis.
Incidence and Mortality Rates	The most serious of the U.S. arboviruses are fortunately rare. About 220 cases have been confirmed since 1964 with an average rate of 5 cases per year. About a third of people who contract EEE die from it. Children are more likely to survive but also to suffer complications afterward.
Age Risk Groups	Adults over age 50 and children under age 15.
Western Equine Encephalitis
Virus Family	Togaviridae (genus Alphavirus)
U.S. Geographic Areas	Farming areas in western and central Plains and Rocky Mountain states west of the Mississippi.
Symptom Onset	5 - 10 days following infection.
Incidence and Mortality Rates	Very rare. There was only one case reported between 1995 and 2000. Mortality rate is 3 - 4%; 30% of survivors have complications afterward. Most severe in children, especially those younger than 1 year. Infants may suffer permanent neurological damage.
Age Risk Groups	Infants younger than 12 months.
St. Louis Encephalitis
Virus Family	Flaviviridae (genus Flavivirus)
U.S. Geographic Areas	Takes its name from an epidemic in St. Louis, but outbreaks have occurred in wider geographic areas, especially in midwestern and southeastern states, and can occur in rural or urban areas. As of 2000, the highest numbers of total cases have been reported in Texas (970), Illinois (695), Ohio (440), Indiana (368), and Florida (379).
Symptom Onset	7 - 10 days following infection.
Incidence and Mortality Rates	Although over 4,500 cases have been reported since 1964, the average number of cases has been declining with a yearly average of only 11 cases between 1995 and 2000. Mortality rate of between 3 - 30%, with about 5% of survivors suffering complications afterward.
Age Risk Groups	Elderly adults (over age 60) are at highest risk, and the disease is most severe in this age group. Younger people usually experience mild, flu-like symptoms.
La Crosse Encephalitis
Virus Family	Bunyaviridae (genus Bunyavirus)
U.S. Geographic Areas	Occurs most frequently in upper Midwestern, southeastern (Appalachia), and mid-Atlantic states. Most cases have occurred in Ohio and Wisconsin. Unlike other encephalitis viruses which originate in birds, La Crosse encephalitis is transmitted to mosquitoes from infected chipmunks and squirrels.
Symptom Onset	5 - 10 days following infection.
Incidence and Mortality Rates	An average of 70 - 100 cases reported per year. Mortality rates are less than 1%. More common and severe in children under age 16.
Age Risk Groups	Children younger than 16 years.
West Nile Encephalitis
Virus Family	Flaviviridae (genus Flavivirus).
U.S. Geographic Areas	Cases have been reported throughout the mainland United States. In 2007, the majority of West Nile encephalitis cases occurred in Colorado, California, and North Dakota.
Symptom Onset	3 - 14 days following infection.
Incidence and Mortality Rates	In 2007, 3,510 cases of WNV were reported to the CDC, with 109 deaths. Of all the reported cases, 65% were due to West Nile fever. A third of those who contracted WNV had more severe conditions, such as meningitis and encephalitis. However, most cases of West Nile virus do not produce symptoms, and are not reported, so these numbers imply a more worrisome picture than actually exists. In fact, fewer than 1% of people who are infected with WNV go on to develop neurological disease.
Age Risk Groups	Adults over age 50.

West Nile Virus (WNV). Until 1999, the West Nile virus was generally restricted to Africa, the Middle East, southwestern Asia, eastern Europe, and Australia. It emerged in the United States with the first outbreak in New York City in 1999. WNV is now found in birds and mosquitoes in every state except Alaska and Hawaii. Human cases of West Nile encephalitis have been reported throughout the continental United States.

How WNV Is Transmitted. WNV, discovered in Uganda in 1937, circulates primarily between birds and mosquitoes and can be carried long distances by migrating birds. In a given geographic area, the appearance of the virus among birds and mosquitoes generally precedes infection in humans. WNV has infected over 110 species of birds. In addition to mosquito-to-human transmission, other causes of human infection have included blood transfusions and organ transplantation. The U.S. now uses screening tests to detect West Nile virus in donated blood and organs. There have also been cases of mother-to-child transmission during pregnancy. However, a 2006 study reported that most pregnant women who are infected with WNV deliver healthy babies. It is still not clear if WNV can be transmitted through breast milk.

Severity of WNV. About 80% of people infected with WNV will not have any symptoms. Twenty percent will develop West Nile fever (which includes fever, headache, and occasional skin rash). Less than 1% of infected people will develop neuroinvasive disease, the most severe form of WNV.

Neuroinvasive disease affects the nervous system and includes encephalitis, meningitis, and poliomyelitis. People over age 50 and those with weakened immune systems are at the greatest risk for neuroinvasive disease. The fatality rate for those afflicted ranges from 3 - 15%. Neuroinvasive disease symptoms include high fever, headache, stiff neck, stupor, disorientation, coma, tremors, convulsions, muscle weakness, and paralysis. Preliminary research is currently being conducted on vaccines to prevent WNV and antiviral drugs to treat it.

Although West Nile fever is considered to be less serious than West Nile neuroinvasive disease, an important 2006 study found that both conditions can cause long-term health complications. Researchers found that more than a year after being diagnosed with WNV, half of patients complained of neurological and psychological symptoms, including fatigue, memory problems, headaches, depression, and tremors. Patients who had West Nile fever were as likely to experience these problems as those who had WNV-associated encephalitis or meningitis.

Tick-borne encephalitis (TBE) is commonly found in many countries throughout Europe, Asia, and the former Soviet Union, but it is reported only rarely in the U.S. Powassan encephalitis is the main tick-borne encephalitis found in the United States and Canada. Cases of tick-borne encephalitis have also been reported from Rocky Mountain spotted fever, but this is a bacterial (not viral) infection.

Enteroviruses include various viruses that enter the body through the gastrointestinal tract. They account for between 10 - 20% of viral encephalitis cases. The group A coxsackievirus has been detected in infants and children with encephalitis and is among the important viruses in the class. (It should be noted that the enteroviruses are nearly as common as cold viruses and are rarely serious.) Enteroviruses can be spread through food or water contaminated by trace amounts of fecal material and through sneezing and coughing.

The herpes virus group includes a number of common infections, including herpes simplex, varicella-zoster (the cause of chickenpox and shingles), cytomegalovirus, herpes virus 6, and Epstein-Barr (EB) virus (the cause of mononucleosis). About 2,100 people are hospitalized each year from herpes-associated encephalitis. These viruses share certain features, including the capacity to cause an infection and then to go into hiding. They can lie dormant for periods of time as short as months or as long as a lifetime. In a few cases, when the viruses reactivate, they cause encephalitis. In fact, some evidence suggests that varicella-zoster, cytomegalovirus, and Epstein-Barr (EB) virus may be more common causes of encephalitis than previously thought. In most cases, however, encephalitis from these viruses occurs in people with impaired immune systems, such as people with HIV or organ transplant patients.

Herpes Simplex Virus. Herpes simplex virus (HSV) is the most common cause of encephalitis in developed countries and is responsible for about 10 - 20% of all adult cases of viral encephalitis. There are two distinct types of the herpes simplex virus: HSV-1 (commonly associated with oral herpes) and HSV-2 (which usually causes genital herpes, although HSV-1 can also cause this form). HSV-2 causes 70 - 90% of encephalitis cases in neonatal infants; the virus is transmitted through the mother's genital secretions. Although HSV-1 is the primary culprit in most adult cases of herpes encephalitis, HSV-2 may also cause a small number of these cases.

Herpes simplex encephalitis is the only effectively treatable form of encephalitis, but treatment (typically intravenous acyclovir) must be administered within the first few days of symptom onset. If left untreated, the mortality rate for patients with HSV-1 is about 70%; if treated, the mortality rate declines to 30%. The mortality rate for neonatal HSV-2 encephalitis ranges from 15 - 57%. [For more information, see In-Depth Report #52: Herpes simplex.]

Varicella-Zoster Virus. The varicella-zoster virus is responsible for both chickenpox (when the virus is called varicella) and shingles (when it is referred to as herpes zoster ). Chickenpox is the initial infection, after which the virus remains dormant, often for a lifetime. If it erupts, usually years later, is does so in the form of shingles. Encephalitis caused by varicella can occur in both children and adults and be very serious. If it occurs as a result of herpes zoster in adults, the brain inflammation tends to be mild, except in immunocompromised patients. In such cases, symptoms can appear weeks to months after an attack of shingles and resemble those of a stroke. Fortunately, encephalitis is rare with both varicella and zoster. [For more information, see In-Depth Report #82: Shingles and chickenpox (varicella-zoster virus).]

Epstein-Barr Virus. Epstein-Barr virus is the cause of infectious mononucleosis, which is most common in children and young adults. Symptoms of the disease are severe fatigue, headache, sore throat, and fever. In 1% of cases, neurological complications occur about 1 - 3 weeks after the onset of the infection. If encephalitis develops, it is almost always mild with full recovery.

Cytomegalovirus Encephalitis. Cytomegalovirus is also very common and usually mild. In immunocompromised patients, such those with AIDS, it can be dangerous, with severe complications including encephalitis.

Rabies. The rabies virus is transmitted from the saliva of an infected animal. The encephalitis it causes is virtually always fatal but is very rare in the U.S. Only one or two cases are typically reported each year, often from contact with bats.

Encephalitis Associated with Childhood Diseases. Encephalitis occurs rarely after common childhood infections, such as rubella, measles, and mumps. Immunizations have almost completely eliminated these infections in developed countries. Measles encephalitis still sometimes occurs in immunocompromised children. Rarely, influenza has caused acute encephalitis, usually in children. (Flu vaccinations are important in preventing these events.) Although there used to be concern that diphtheria-pertussis-tetanus and measles-mumps-rubella vaccines could cause encephalitis, recent research indicates that these childhood vaccines are very safe and do not increase encephalitis risk.

Adenoviruses. Adenoviruses were first identified in 1953 from infected tonsils and adenoids. The viruses can cause respiratory or gastrointestinal infections that are usually mild. In rare cases, adenoviruses can cause encephalitis or meningoencephalitis, which can be fatal in 30% of patients. Symptoms include lethargy, confusion, coma, and symptoms of meningitis (stiff neck, headache, and vomiting).

Toxoplasmosis. Encephalitis from toxoplasmosis, which is transmitted in a cat's fecal matter, results in 2,100 hospitalizations a year, which rivals herpes as the most common infectious cause of encephalitis. However, this condition causes very mild symptoms in most people. People with HIV and impaired immune systems are at risk for more severe forms. In addition, the effects on the fetus in a pregnant women infected with toxoplasmosis can be devastating. It can be treated with antibiotics, particularly those that treat parasites.

Raccoon Roundworm. Raccoon roundworm (Baylisascaris procyonis) is a large parasitic worm that lives in the intestines of raccoons. In one Wisconsin study, half the raccoons tested were infected. Humans usually become infected by ingesting the worm's eggs through accidental contact with soil, wood chips, or tree bark contaminated with raccoon feces. The worm is harmless in raccoons but can produce severe central nervous system disease, including encephalitis, in people. At least 12 severe cases have been reported in the U.S. since 1981, most in children younger than 6 years of age (who are at higher risk because of their tendency to put their fingers or other objects into their mouths). Prompt treatment with larvae-killing drugs, such as albendazole, or anti-inflammatory drugs is not consistently effective, so it is extremely important to avoid infection. Raccoons should not be kept as pets. Eliminate access to food sources, like garbage cans and bird feeders, which will attract raccoons. Raccoon nests should be sealed off while raccoons are absent. Burning any contaminated materials is the most effective method of disposal. If burning is not feasible, contaminated substances should be buried deeply in a location remote from human activity. Wearing disposable gloves, boots, and a dust mask is important. Decks, woodpiles, and other surfaces can be decontaminated with boiling water.

Other Parasitic Infections. Encephalitis may be caused by other parasitic infections, such as toxocariasis (from roundworms found in dogs and cats) or cysticercosi (from food or water contaminated with pork tapeworm eggs). These infections usually cause only chills, fever, and swelling of lymph nodes, though seizures and headaches can occur.

In very rare circumstances, encephalitis may be caused by bacterial or fungal organisms.

Acute disseminated encephalomyelitis (ADEM), also called noninfectious encephalitis, constitutes one-third of all known cases of encephalitis. It is not caused by a virus, although it most often develops in patients 2 - 3 weeks after recovery from a viral illness. (It does not affect children under 2 years old.) Damage to nerve cells in such cases is caused not by the viral infection, however, but most likely by an autoimmune reaction, in which the body's immune system attacks its own brain tissue.

Acute disseminated encephalomyelitis has been reported as a rare complication of childhood illness, including chickenpox, mumps, or measles. Vaccination reduces these risks to nearly insignificant levels. It is a complication of the rabies vaccine in one out of 30,000 cases. Nonspecific respiratory infections are now the most common causes of ADEM, but such cases are also extremely rare.

The inflammation occurs predominantly in the white matter of the brain rather than the gray matter (the usual target of infectious encephalitis). The nerve cells do not die as they do in a viral infection. Rather, the nerve cell coating (called a myelin sheath) is partially destroyed in much the same way as it is in multiple sclerosis. Indeed, the two conditions may at first be difficult to distinguish. Recurrences may occur several months to years after the initial episode.

Symptoms

Symptoms of encephalitis usually appear within 2 days to 2 weeks of exposure to the virus. In milder cases, symptoms may resemble the flu. In severe cases of full-blown encephalitis, symptoms may include:

Behavioral and personality changes
Sensitivity to light
Fever
Headache
Vomiting
Lethargy and reduced consciousness
Seizures -- uncommon with West Nile virus
Memory loss
Stiff neck and back -- accompanied by fever and headache would indicate meningitis
Confusion
Speech, hearing, and vision problems
Muscle weakness
Seizures
Partial paralysis
Loss of consciousness
Coma

Patients experiencing these types of symptoms (especially if they may have recently been bitten by a mosquito or tick of if they have lesions on the lips or genitals) should immediately seek medical treatment.

Symptoms in Infants. Infants with herpes virus encephalitis may develop lesions in the mouth, in the eye, or on the skin 1 - 45 days after birth. Other symptoms include lethargy, seizures, and changes in temperature. Their fontanels, the soft spots on their head where the skull has not yet closed, may bulge outward.

Risk Factors

Encephalitis is a rare disease, extremely uncommon in the U.S. even for people in the risk groups discussed below. Many people fall into the following categories; very few of them will ever contract encephalitis.

Encephalitis can occur at any age; increased age-associated risks depend on the type of encephalitis virus. Newborn infants are particularly at risk for herpes virus. For arboviruses, infants are most vulnerable to Western equine encephalitis. Older children and teenagers are more susceptible to Eastern equine and La Crosse encephalitis. Older and elderly adults are at higher risk for Eastern equine, St. Louis, and West Nile encephalitis.

Immunocompromised Patients

Patients whose immune systems are compromised by conditions such as HIV-AIDS, cancer therapies, or organ transplantation are more susceptible than other individuals to any form of encephalitis. Of particular concern are varicella and cytomegalovirus encephalitis which tend to be more common and deadly in these patients than in the normal population.

U.S. Geographic Regions. The primary risk factor for arbovirus encephalitis is living in areas of possible exposure to virus-carrying mosquitoes. Most viral outbreaks occur in rural or farming areas, but they can also occur in cities. While some forms of arbovirus encephalitis are limited to specific geographical regions, the West Nile virus has become endemic throughout the mainland United States. [See Common Forms of Mosquito-Borne Encephalitis table for more detailed regional information.]

Seasonal Risks. Transmission of arboviruses correlates with the mosquito season and is highest during the months of July through September (late summer through early fall). The ideal conditions for mosquito breeding are a wet spring followed by a hot, dry summer.

Few people in the world have not been infected with at least one of the herpes viruses. Most of these viruses are easily transmitted in body fluids, including from saliva or droplets after people exhale or sneeze. Infants can contract herpes simplex virus from an infected mother during delivery, which can have very serious consequences. [For more information, see In-Depth Report #52: Herpes simplex.]

Prognosis

In most cases of arbovirus infection, symptoms are mild, last 3 - 5 days, and resolve without becoming serious. In fact, the infection is generally unrecognized as anything other than a mild flu.

Prognosis for severe encephalitis depends on many factors, including the following:

Age of the patient -- worse outcomes for infants under age 12 months and adults over age 55
Immune status
Preexisting neurological conditions
Virulence of the virus

In severe cases of encephalitis, the swelling of the brain inside the skull places downward pressure on the brain stem. The brain stem controls vital functions, such as respiration and heartbeat, and if the pressure becomes too severe, these vital functions can cease and cause death.

Coma is a common symptom in patients with severe encephalitis, but does not necessarily predict a fatal or severe outcome. In one study of Eastern equine encephalitis, some survivors averaged 5 days in a coma and had no or only mild-to-moderate complications afterward. One patient was in a coma for 9 days and had only mild complications afterward.

Survivors of encephalitis commonly experience neurologic consequences, which can be long-term and even permanent. The degree and type of brain damage can vary from mild-to-severe and from focal (in one part of the brain) to multifocal (several parts of the brain) to diffuse (throughout the brain).

The location and severity of the infection largely determines the pattern of brain damage and therefore its effects, which can be:

Physical (muscle control)
Behavioral and emotional (personality changes)
Cognitive (memory, speech)
Sensory (vision, hearing)
Some patients who have memory problems and personality changes afterward describe their condition as being an "invisible disease." They appear to be normal to others, but they are plagued with forgetfulness and lapses in attention that have a considerable effect on the quality of their daily lives. Helpful support groups are now available on the Internet.

Diagnosis

In many cases, the symptoms of encephalitis are too similar to aid the doctor in differentiating among the many causes of brain inflammation. The primary objective in diagnosing viral encephalitis is to determine if it is caused by:

Arboviruses or other viruses that can be managed only by relieving symptoms
Herpes simplex or other conditions that are potentially treatable

If the doctor suspects encephalitis, a scanning technique is often the first diagnostic step. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans may show the extent of the inflammation in the brain and help differentiate encephalitis from other conditions. MRI can detect injuries in parts of the brain that suggest infection with herpes virus at the onset of the disease, while CT scans cannot.

Electroencephalogram (EEG), which records brain waves, may reveal abnormalities in the temporal lobe that are indicative of herpes simplex encephalitis.

When encephalitis is suspected, a sample of cerebrospinal fluid is taken using a lumbar puncture, which involves inserting a needle between two vertebrae in the patient's lower back. The sample is taken to count white blood cells and identify specific blood cell types, to measure proteins and blood sugar levels, and to determine spinal fluid pressure. Doctors use cerebrospinal fluid to test for herpes simplex encephalitis and to look for the presence of antibodies to the West Nile virus. While cerebrospinal fluid tests may help diagnose encephalitis, they cannot provide information on how severe the disease will be.

Blood tests are used to test for West Nile virus and other arbovirus infections.

If necessary, tiny samples of brain tissue are surgically removed for examination and testing for the presence of the virus. Tissue is prepared using staining techniques and then viewed under an electron microscope. In a few cases, the viruses in brain cells are able to be cultured; that is, the viruses can actually be made to replicate in samples. A brain biopsy is the gold standard for diagnosing rabies.

Treatment

With the exception of herpes simplex and varicella-zoster encephalitis, the viral forms of encephalitis are not treatable. The primary objective is to diagnose the patient as soon as possible so they receive the right medicines to treat the symptoms. It is very important to lower fever and ease the pressure caused by swelling of the brain.

Patients with very severe encephalitis are at risk for body-wide (systemic) complications including shock, low oxygen, low blood pressure, and low sodium levels. Any potentially life-threatening complication should be addressed immediately with the appropriate treatments.

Since it is difficult to determine the cause of encephalitis, and rapid treatment is essential, it is common to give the patient medication for the symptoms that respond to therapy without waiting to determine the cause of the illness.

Some experts advise immediately administering intravenous acyclovir, the standard treatment for herpes simplex encephalitis, to all patients whose symptoms indicate encephalitis.
Corticosteroids, which reduce inflammation, may also be administered immediately.
Antibiotics, which attack bacteria but not viruses, are used in case the cause of the symptoms is bacterial meningitis.

All encephalitis treatments are aimed at reducing symptoms.

Seizures may be prevented by using fosphenytoin (Cerebyx).
Seizures may be treated with intravenous lorazepam (Ativan).
Sedatives may be prescribed for irritability or restlessness.
Simple pain relievers may be used for fever and headache.
In patients who are otherwise stable, the only other treatment measures are to keep the head elevated and monitor the patient's status.

Intravenous acyclovir is the treatment of choice for encephalitis caused by herpes simplex virus (HSV) or varicella-zoster virus. Treatment must be initiated within 2 days of symptoms for the best outcome. In nearly all cases, the virus clears within 2 weeks of treatment. If it does not, medications are continued for another 2 weeks. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.

Acyclovir is usually administered in the hospital. However, some patients may be safely treated with intravenous medications at home after the first few days with close monitoring by a health professional. Valacyclovir and famciclovir may be used for the treatment of non-life-threatening HSV infection.

About 25% of patients who have been successfully treated for herpes encephalitis have a relapse. Early diagnosis and treatment may help reduce this risk. Doctors are investigating if a 3-month course of oral valacyclovir will improve remission rates after a patient completes treatment with intravenous acyclovir. Foscarnet (Foscavir), another powerful antiviral drug known as a pyrophosphate analogue, may be useful for herpes simplex viral strains that have become resistant to acyclovir.

No other drugs have been effective for treating arboviruses, including West Nile virus. A number of drugs used to treat other virus infections are being investigated. They include ribavirin (an antiviral drug used to treat influenza), interferon alfa 2a (Roferon-A) and other interferons, immunoglobulin G, and glycyrrhizin (a compound in licorice root with anti-viral activity). Researchers with the U.S. National Institutes of Health are investigating Omr-IgG-am, a blood-derived product that contains WNV antibodies, which can be given intravenously.

ADEM is usually treated with high-dose intravenous methylprednisolone, a powerful anti-inflammatory drug known as a corticosteroid. Intravenous immunoglobulin (IVIG), alone or in combination with methylprednisolone, is also showing promise in certain patients, including children with severe ADEM.

Vaccinations

Certain vaccinations can help prevent the diseases that can lead to encephalitis.

Measles used to be a very common childhood disease. In about 1 in 1,000 patients it can lead to encephalitis or death. The risk for these severe complications is highest in the very young and very old. Aggressive vaccination programs have reduced the incidence of measles in the U.S. to fewer than 100 cases a year. Rarely, patients who receive the live-measles vaccine develop encephalopathy (brain damage), but the risk is far lower than brain problems occuring from the disease itself.

Herpes zoster, or shingles, is a reactivation of the varicella virus, which causes chickenpox. Children (and adults who do not have a history of infection and who lack evidence of immunity) should receive 2 doses of the chickenpox vaccine. In 2006, a vaccine for shingles became available for adults age 60 years and older. [For more information, see In-Depth Report #82: Shingles and Chickenpox.]

Researchers are investigating a number of vaccines against the flavivirus family of arboviruses.

A vaccine (JE-VAX) is currently available for Japanese encephalitis. In travelers, it is only recommended for those visiting rural areas in high-risk Asian countries for more than 30 days. These countries include China, Korea, India and neighboring areas, and Southeast Asia. The disease may occur with lower frequency in Japan, Taiwan, Singapore, Hong Kong, and eastern Russia. A new type of Japanese encephalitis virus vaccine is currently in clinical trials.

Another type of vaccine (FSME-IMMUN) is used to prevent tick-borne encephalitis (TBE) in travelers visiting regions where this type of encephalitis is prevalent. TBE is found mainly in Eastern Europe, China, North Africa, and Russia. This vaccine is available in many European countries, but it is not yet approved in the United States.

Two types of vaccines, chimeric and DNA, are under investigation for West Nile virus, but it will be several years before these vaccines could become commercially available.

Anyone exposed to bats, or the secretions of an animal suspected of having rabies, should be evaluated for post-exposure rabies vaccine. Exposed individuals may also receive immune globulin unless they were previously vaccinated. Local health authorities are generally consulted. When the saliva of a potentially infected animal is exposed to an open wound or mucous membrane, treatment is generally warranted. However, the need to administer rabies immunization or immune globulin after saliva exposure to intact skin is not as clear. Veterinarians and animal handlers should be vaccinated. This does not eliminate the need for treatment if they are exposed to rabies, but it reduces the intensity of the treatment. Side effects of these shots include:

Pain
Redness
Headache
Stomach pain
Nausea
Dizziness
Muscle aches
Swelling at the injection site

Allergic response can occur after the first shot and as many as 21 days after a booster shot. Rare cases of neurological disorders have been reported that cause pain and paralysis in the legs and arms, which clear up in about 12 weeks.

Prevention

The risk for mosquito-born infections is highest between dusk and dawn, when mosquitoes feed. A good insect repellent is very helpful in reducing the risk for vector-borne disease. The most complete personal protection program for adults and most children is to apply the insect repellant DEET to the skin, and also permethrin to clothing and other surfaces.

DEET. Most insect repellents contain the chemical DEET (N,N-diethyl-meta-toluamide), which remains the gold standard of currently available mosquito and tick repellents. DEET has been used for more than 40 years and is safe for most children when used as directed. Comparison studies suggest that DEET preparations are the most effective insect repellents now available.

Concentrations range from 4% to almost 100%. The concentration determines the duration of protection. Experts recommend that most adults and children over 12 years old use preparations containing a DEET concentration of 20 - 35% (such as Ultrathon), which provides complete protection for an average of 5 hours. (Higher DEET concentrations may be necessary for adults who are in high-risk regions for prolonged periods.)

Never use DEET products should on infants younger than 2 months. According to the Environmental Protection Agency (EPA), DEET products can safely be used on all children age 2 months and older. The EPA recommends that parents check insect repellant product labels for age restrictions. If there is no age restriction listed, the product is safe for any age. The American Academy of Pediatrics recommends that children use concentrations of 10% or less; 30% DEET is the maximum concentration that should be used for children. When deciding what concentration is most appropriate, parents should consider the amount of time that children will be spending outside, and the risk of mosquito bites and mosquito-borne disease.

When applying DEET, take the following precautions:

Do not use on the face, and apply only enough to cover exposed skin on other areas.
Do not over apply, and do not use under clothing.
Do not apply over any cuts, wounds, or irritated skin.
Only parents or an adult should apply repellent to a child. They should first put DEET on their own hands and then apply it to the child. They should avoid putting DEET not only near the child's eyes and mouth but also on the hands (since children frequently touch their faces).
Wash any treated skin after going back inside.
If using a spray, apply DEET outdoors -- never indoors. Spray repellents should not be applied directly on anyone's face.

Other Insect Repellent Products. In 2005, the U.S. Centers for Disease Control (CDC) added two new mosquito repellents to its list of recommended products: Picaridin and oil of lemon eucalyptus.

Picaridin, also known as KBR 3023 or Bayrepel, is an ingredient that has been used for many years in repellents sold in Europe, Latin America, and Asia. A product containing 7% picaridin is now available in the United States. Picaridin can safely be applied to young children and is also safe for women who are pregnant or breast-feeding. According to the CDC, insect repellents containing DEET or picaridin work better than other products.

In scientific tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years.

Permethrin is an insect repellent used as a spray for clothing and bed nets, which can repel insects for weeks when applied correctly. Electric vaporizing mats containing permethrin may be very helpful. A permethrin solution is also available for soaking items, but it should never be applied to the skin. Side effects from direct exposure may include mild burning, stinging, itching, and rash. In general, however, permethrin is very safe and its use may even reduce child mortality rates from malaria. People allergic to chrysanthemum flowers or who are allergic to head-lice scabicides should avoid using permethrin.

Eliminate Sources of Standing Water. Currently, the only proven method for reducing mosquito populations is to eliminate sources of standing water.

Look for any source of standing water, where mosquitoes can breed. For example, discard any rubbish with standing water, such as old tires, cans, and bottles. (Even bottle caps can breed mosquitoes.) Turn over wading pools and wheelbarrows when not in use. Change bird bath water every 3 - 4 days. A product called Mosquito Dunk can be used to prevent breeding in standing water.
Swimming pools and hot tubs should be clean and chlorinated or drained and covered if not in use.
Clean vegetation and debris from the edges of ponds.
Keep gutters clean and unclogged.

Mosquito Traps. Mosquito traps use various methods for repelling or attracting and trapping the insects. Effective traps are expensive, and they usually require electricity or propane, which adds to the cost. Use mosquito trap machines only outdoors. While many traps can draw in significant numbers of mosquitoes, they have limitations. Do not rely on them for sole protection.

All baits should aim to attract the female mosquito, which is the primary transmitter of the viruses. However, different baits may be more or less effective. Some may even attract one species and not others. For example, a comparative study of three traps that used similar attractants found that after 20 hours, the Magnet Liberty and Mosquito Trap MK01 attracted 75% of mosquitoes in a single area, while the Sonic Web had attracted only 25%. However, all three traps tended to attract twice as many Aedes mosquitoes (which carry La Cross and Eastern Equine encephalitis) as the Culex (which transmits West Nile and St. Louis Encephalitis).

Bug Zappers. Insect light traps (commonly called bug zappers), which attract and electrocute insects, may actually spread viruses and bacteria that are on the insects. They are also not very effective for killing female mosquitoes.

Encouraging Natural Defenders. Some attempts have been made to control mosquito populations with natural defenders, including building bat and bird houses to attract natural predators or growing certain insect-repellent plants.

Citronella Candles. Burning citronella candles reduces the likelihood of bites. (Indeed, burning any candle helps to some extent, perhaps because the generation of carbon dioxide diverts mosquitoes toward the flame.)

Your home environment, personal hygiene, and what you wear can also help reduce your risk for mosquito bites:

Wear trousers and long-sleeved shirts, particularly at dusk. One survey suggested that this measure may significantly reduce the incidence of mosquito-born disease.
Sleep only in screened areas.
Air-conditioning may reduce mosquito infiltration. Where air-conditioning is not available, fans may be helpful. Mosquitoes appear to be reluctant to fly in windy air.
Don't wear perfumes.
Cover up bare skin after dusk.
Wash your hair at least twice a week.

Public health measures are the best methods for controlling mosquitoes.

Spraying. Local areas that experience outbreaks of encephalitis from mosquitoes usually have a spraying program.

Insecticides containing synthetic pyrethroids (permethrin, resmethrin, and sumithrin) are generally recommended by consumer groups as being the most effective and the least toxic to people (although they are toxic to fish and bees).
Malathion and naral -- another pesticide -- are organophosphates and approved for spraying mosquitoes. Malathion specifically has been widely used in a number of areas. Organophosphates, however, can have toxic effects on the nervous system. Some people, for example, have reported being sick after exposure to Malathion. In addition, there is a risk that mosquitoes will develop resistance to it.

Report Dead Birds. Dead birds may be indicators that the West Nile virus has reached a specific region. Report any dead birds to your local public health authorities. You should never touch a dead bird with your bare hands.

Resources

www.cdc.gov -- The U.S. Centers for Disease Control (CDC)
www.cdc.gov/ncidod/dvbid/arbor -- CDC website for arboviruses
www.cdc.gov/ncidod/dvbid/westnile -- CDC West Nile virus website
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.mosquito.org -- American Mosquito Control Association
www.npic.orst.edu/wnv -- National Pesticide Information Center's West Nile virus resource guide

References

Bleck TP. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Modlin JF. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Nath A, Berger JR. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Whitley RJ. In: Goldman L and Ausiello DA, eds. Cecil Medicine. 23rd edition. Saunders; 2007.

Review Date:
1/26/2008
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

Alcoholism

FitSugar — Wed, 08 Oct 2008 17:35:36 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment for Alcoholism...
Treatment for Alcohol Withd...
Therapy
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Research

Topiramate (Topamax), an anticonvulsant drug used to treat epilepsy, is showing promise as a treatment for alcohol dependence. In a 2007 study published in the Journal of the American Medical Association, patients who took topiramate had fewer heavy drinking days, fewer drinks per day, and more days of not drinking at all than patients who received placebo.

Alcohol and Heart Disease

Heart disease is one of the leading causes of death among people who are heavy drinkers. Alcohol abuse and dependence increase the risks for unhealthy cholesterol levels, high blood pressure, heart failure, and stroke. Although the heart benefits of moderate alcohol use are widely discussed in the popular media, to date there are no definitive scientific studies that prove that alcohol consumption is beneficial to overall health.

The American Heart Association recommends that people who drink alcohol do so in moderation (one to two drinks a day for men, one drink a day for women). If you don’t drink, the American Heart Association advises against starting to drink to reduce the risk of heart disease. The best methods for preventing heart disease are exercise, healthy diet, and avoiding all forms of tobacco exposure.

Alcohol and Cancer

Long-term heavy alcohol use may increase the risks for many types of cancer including stomach, colorectal, mouth, tongue, throat, liver, and breast cancers. To reduce breast cancer risk, the American Cancer Society recommends that women limit their amount of alcohol consumption. Women who are at high risk for breast cancer should consider not drinking at all.

Introduction

Alcoholism is a chronic, progressive, and often fatal disease. It is a primary disorder and not a symptom of other diseases or emotional problems. The chemistry of alcohol allows it to affect nearly every type of cell in the body, including those in the central nervous system. After prolonged exposure to alcohol, the brain becomes dependent on it. The severity of this disease is influenced by factors such as genetics, psychology, culture, and response to physical pain.

Alcoholism is a chronic illness marked by dependence on alcohol consumption. It interferes with physical or mental health, and social, family, or job responsibilities. This addiction can lead to liver, circulatory, and neurological problems. Pregnant women who drink alcohol in any amount may harm the fetus.

Alcoholism, alcohol dependence, and alcohol abuse are associated with the following:

The only indication of early alcoholism may be the unpleasant physical responses to withdrawal that occur during even brief periods of abstinence.
Alcoholics have little or no control over the quantity they drink or the duration or frequency of their drinking.
Alcoholics are preoccupied with drinking, deny their own addiction, and continue to drink even though they are aware of the dangers.
Over time, some alcoholics become tolerant to the effects of drinking and require more alcohol to become intoxicated, creating the illusion that they can "hold their liquor."
Alcoholics may have blackouts after drinking and have frequent hangovers that cause them to miss work and other normal activities.
Alcoholics might drink alone and start their drinking early in the day.
Alcoholics periodically quit drinking or switch from hard liquor to beer or wine, but these periods rarely last.
Severe alcoholics often have a history of accidents, marital and work instability, and alcohol-related health problems.
Episodic violent and abusive incidents involving spouses and children and a history of unexplained or frequent accidents are often signs of drug or alcohol abuse.

Alcoholism can develop insidiously, and often there is no clear line between problem drinking and alcoholism. Eventually alcohol dominates thinking, emotions, and actions and becomes the primary means through which a person can deal with people, work, and life.

In addition to alcohol dependence, experts are now defining alcohol use by levels of harm that it may be causing. This information is useful to determine possible interventions at earlier stages. The following categories of alcohol use and abuse use a definition of one drink as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces (a jigger) of 90-proof liquor.

Moderate Drinking. Moderate drinking, particularly red wine, appears to offer health benefits. Moderate drinking is defined as equal to or less than two drinks a day for men and one drink a day for women.

Hazardous (Heavy) Drinking. Hazardous drinking puts people at risk for adverse health events. People who are heavy drinkers consume:

More than 14 drinks per week, or four to five drinks at one sitting, for men
More than seven drinks per week, or three drinks at one sitting, for women
Frequent intoxication

Harmful Drinking. Drinking is considered harmful when alcohol consumption has actually caused physical or psychologic harm. This is determined by:

Clear evidence that alcohol is responsible for such harm.
The nature of that harm can be identified.
Alcohol consumption has persisted for at least a month or has occurred repeatedly for the past year.

Certain people are at much higher risk for harmful drinking, such as older individuals with high blood pressure or those taking medications for arthritis or pain.

Alcohol Abuse. People with alcohol abuse have one or more of the following alcohol-related problems over a period of 1 year:

Failure to fulfill work or personal obligations
Recurrent use in potentially dangerous situations
Problems with the law
Continued use in spite of harm being done to social or personal relationships

Alcohol Dependence. People who are alcohol dependent have three or more of the following alcohol-related problems over a year:

Increased amounts of alcohol are needed to produce an effect
Withdrawal symptoms or drinking alcohol is used to avoid these symptoms
Drinks more over a given period than intended
Unsuccessful attempts to quit or cut down
Gives up significant leisure or work activities
Continues to drink in spite of the knowledge of its physical or psychological harm to oneself or others

Two-thirds of those with alcohol dependence continued to be dependent on alcohol after 5 years.

Causes

People have been drinking alcohol for about 15,000 years. Drinking steadily and consistently over time can produce dependence and cause withdrawal symptoms during periods of abstinence. This physical dependence, however, is not the sole cause of alcoholism. To develop alcoholism, other factors usually come into play, including biology, genetics, culture, and psychology.

Genetic factors play a significant role in alcoholism and may account for about half of the total risk for alcoholism. The role that genetics plays in alcoholism is complex, however, and it is likely that many different genes are involved. Research suggests that alcohol dependence, and other substance addictions, may be associated with genetic variations in 51 different chromosomal regions.

Researchers are investigating a number of inherited traits that make particular individuals susceptible to this disorder:

The amygdala is an area of the brain thought to play a role in the emotional aspects of craving, which can lead to addiction. Some studies indicate that the amygdala is smaller in subjects with family histories of alcoholism, suggesting that inherited differences in brain structure may affect risk. Other studies suggest that certain brain chemicals (neurotransmitters) and proteins in the amygdala region may be involved in the link between anxiety and alcoholism.
Some studies indicate that people may inherit a lack of the warning signals that ordinarily make people stop drinking. Research suggests this factor may contribute to 40 - 60% of alcoholism cases related to genetic factors. (Even in the absence of genetic factors, repeated exposure to alcohol increases the ability to tolerate larger amounts before experiencing behavioral impairment.)
Some people with alcoholism may have an inherited dysfunction in the transmission of serotonin. Serotonin is a brain chemical messenger (neurotransmitter). It is important for well-being and associated behaviors (eating, relaxation, and sleep). Abnormal serotonin levels are associated with high levels of tolerance for alcohol. They are also linked to impulsivity and aggressiveness. These behaviors can predispose people to drink and can increase the risk for dangerous behaviors and suicide in people who are alcohol dependent.
Dopamine is another neurotransmitter associated with alcoholism and other addictions. Research indicates that high levels of the D2 dopamine receptor may help inhibit behavioral responses to alcohol, and protect against alcoholism, in people with a family history of alcohol dependence.

Even if genetic factors can be identified, however, they are unlikely to explain all cases of alcoholism. It is important to understand that whether they inherit the disorder or not, people with alcoholism are still legally responsible for their actions. Inheriting genetic traits does not doom a child to an alcoholic future. Environment, personality, and emotional factors also play a strong role.

Alcohol has widespread effects on the brain and can affect neurons (nerve cells), brain chemistry, and blood flow within the frontal lobes of the brain. Researchers are particularly interested in systems of neurotransmitters (chemical messengers) in the brain that are affected by alcohol. Some research is focusing on the way these neurotransmitters are employed in the brain after long-term alcohol use in order to adapt to the cravings and pain of withdrawal. Such chemical changes may lead to dependency or to relapse after quitting in two ways:

They increase the need to reduce agitation
They increase the desire to restore pleasurable feelings

When a person who is dependent on alcohol stops drinking, chemical responses create an overexcited nervous system and agitation by changing the level of chemicals that inhibit impulsivity or stress and excitation. High norepinephrine levels, a chemical the brain produces more of when drinking is stopped, in fact, may be the primary factor in withdrawal symptoms, such as an increase in blood pressure and heart rate. This hyperactivity in the brain produces an intense need to calm down and to use more alcohol. One study suggested that the need to relieve agitation may be the more important factor in causing a relapse than restoring mood.

Drinking alcohol stimulates the release of neurotransmitters (serotonin, dopamine, and opioid peptides) that produce pleasurable feelings such as euphoria, a sensation of being rewarded, and a sense of well-being.

Over time, however, heavy alcohol use appears to deplete the stores of dopamine and serotonin. Persistent drinking, therefore, eventually fails to restore mood, but by then the drinker has been conditioned to believe that alcohol will improve spirits (even though it does not).

Between 80 - 90% of people treated for alcoholism relapse, even after years of abstinence. Patients and their caregivers should understand that relapses of alcoholism are analogous to recurrent flare-ups of chronic physical diseases. Factors that place a person at high risk for relapse include:

Frustration and anger
Social pressure
Internal temptation

Mental and Emotional Stress. Alcohol blocks out emotional pain and is often perceived as a loyal friend when human relationships fail. It is also associated with freedom and with a loss of inhibition that offsets the tedium of daily routines. When the alcoholic tries to quit drinking, the brain seeks to restore what it perceives to be its equilibrium. The brain's best weapons to achieve this are depression, anxiety, and stress (the emotional equivalents of physical pain), which are produced by brain chemical imbalances. These negative moods continue to tempt alcoholics to return to drinking long after physical withdrawal symptoms have abated.

It is important to realize that any life change, even changes for the better, may cause temporary grief and anxiety. With time and the substitution of healthier pleasures, this emotional turmoil weakens and can be overcome.

Co-dependency. Many aspects of the ex-drinker's relationships change when drinking stops, making it difficult to remain abstinent:

One of the most difficult problems that occur is being around other people who are able to drink socially without danger of addiction. A sense of isolation, a loss of enjoyment, and the ex-drinker's belief that pity, not respect, is guiding a friend's attitude can lead to loneliness, low self-esteem, and a strong desire to drink again.
Friends may not easily accept the sober, perhaps more subdued, ex-drinker. Close friends and even intimate partners may have difficulty in changing their responses to this newly sober person and, even worse, may encourage a return to drinking.
To preserve marriages, spouses of alcoholics often build their own self-images on surviving or handling their mates' difficult behavior and then discover that they find it difficult to adjust to new roles and behaviors.

In such cases, separation from these "enablers" may be necessary for survival. It is no wonder that, when faced with such losses, even if they are temporary, a person returns to drinking. The best course in these cases is to encourage close friends and family members to seek help as well. Fortunately, groups such as Al-Anon exist for this purpose.

Social and Cultural Pressures. The media portrays the pleasures of drinking in advertising and programming. The medical benefits of light-to-moderate drinking are frequently publicized, giving ex-drinkers the spurious excuse of returning to alcohol for their health. These messages must be categorically ignored and acknowledged for what they are: An industry's attempt to profit from potentially great harm to individuals.

Risk Factors

About 90% of adults in the U.S. drink alcohol. Every day, more than 700,000 Americans are being treated for alcoholism. In addition, up to half of American men have problems that are caused by alcohol.

Some researchers have categorized people with alcoholism as Type 1 or Type 2.

Type 1 individuals are more often women. They typically become alcoholic at a later age, have less severe symptoms or fewer psychiatric problems, and have a better outlook on life than those classified as type 2.
Type 2 people are more likely to be male. They tend to become alcoholic at an early age and have a high family risk for alcoholism, more severe symptoms, and a negative outlook on life.

Not only do these two groups tend to respond differently to psychotherapeutic approaches, but they may also respond differently to medications.

Drinking in Adolescence. About half of under-age Americans have used alcohol. About 2 million people ages 12 - 20 are considered heavy drinkers, and 4.4 million are binge drinkers. Anyone who begins drinking in adolescence is at risk for developing alcoholism. The earlier a person begins drinking, the greater the risk. A 2006 survey of over 40,000 adults indicated that among those who began drinking before age 14, nearly half had become alcoholic dependent by the age of 21. In contrast, only 9% of people who began drinking after the age of 21 developed alcoholism.

Young people at highest risk for early drinking are those with a history of abuse, family violence, depression, and stressful life events. People with a family history of alcoholism are also more likely to begin drinking before the age of 20 and to become alcoholic. Such adolescent drinkers are also more apt to underestimate the effects of drinking and to make judgment errors, such as going on binges or driving after drinking, than young drinkers without a family history of alcoholism.

Drinking in the Elderly Population. Although alcoholism usually develops in early adulthood, the elderly are not exempt. In fact, doctors may overlook alcoholism when evaluating elderly patients, mistakenly attributing the signs of alcohol abuse to the normal effects of the aging process. A survey of adults over 60 reported that 15% of men and 12% of women were hazardous drinkers, and 9% of men and 3% of women were alcohol dependent.

Alcohol also affects the older body differently. People who maintain the same drinking patterns as they age can easily develop alcohol dependency without realizing it. It takes fewer drinks to become intoxicated, and older organs can be damaged by smaller amounts of alcohol than those of younger people. Also, up to one-half of the 100 most prescribed drugs for older people react adversely with alcohol. Medications used for arthritis or pain pose a particular danger for interaction with alcohol.

Most alcoholics are men, but the incidence of alcoholism in women has been increasing over the past 30 years. Studies indicate that about 7% of men and 2.5% of women abuse alcohol. However, studies suggest that women are more vulnerable than men to many of the long-term consequences of alcoholism. For example, women are more likely than men to develop alcoholic hepatitis and to die from cirrhosis, and women are more vulnerable to the brain cell damage caused by alcohol.

Individuals who were abused as children have a higher risk for substance abuse later on. In one study, 72% of women and 27% of men with substance abuse disorders reported physical or sexual abuse or both. They also had worse response to treatment than those without such a history.

Overall, there is no difference in alcoholic prevalence among African-Americans, Caucasians, and Hispanic-Americans. Some population groups, however, such as Native Americans, have an increased incidence of alcoholism while others, such as Jewish and Asian Americans, have a lower risk. Although the biological or cultural causes of such different risks are not known, certain people in these population groups may have a genetic susceptibility or invulnerability to alcoholism because of the way they metabolize alcohol.

Psychiatric Disorders. Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Likewise, a large proportion of alcohol-dependent people suffer from an accompanying psychiatric or substance abuse disorder. Either anxiety or depression may increase the risk for self-medication with alcohol. Depression is the most common psychiatric problem in people with alcoholism or substance abuse.

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.

Specific anxiety disorders, such as panic disorders and social phobia, may pose particular risks for alcohol and substance abuse. Social phobia causes an intense fear of being publicly scrutinized and humiliated. Panic disorders cause intense anxiety and panic attacks. People with these disorders may use alcohol as a way to become less inhibited in public situations or to calm feelings of panic. While anxiety disorders are found in about 15% of adults overall, over 50% of people with alcohol abuse problems suffer from these conditions. People who have anxiety disorders are more likely to resume drinking after treatment for alcohol dependence. [For more information, see In-Depth Report #28: Anxiety.]

Long-term alcoholism itself may cause chemical changes that produce anxiety and depression. In fact, a study on elderly people with depression reported that when even moderate drinkers reduced consumption, their mood improved. Studies also indicate that alcohol use may promote panic attacks. It is not always clear, then, whether people with emotional disorders are self-medicating with alcohol, or whether alcohol itself is producing mood swings.

Behavioral Disorders and Lack of Impulse Control. Studies are also finding that alcoholism is strongly related to impulsive, excitable, and novelty-seeking behavior, and such patterns are established early on. Children who later become alcoholics or who abuse drugs are more likely to have less fear of new situations than others, even if there is a greater risk for harm than in nonalcoholics. Specifically, children with attention deficit hyperactivity disorder (ADHD), a condition that shares these behaviors, have a higher risk for alcoholism in adulthood. The risk is especially high in children with ADHD and conduct disorder.

Alcoholism is not restricted to any social or economic levels. For example, a thorough 1996 study reported no higher prevalence of alcoholism among adult welfare recipients than in the general population (about 7%). There was also no difference in prevalence between African-Americans and Caucasians in low-income groups. On the other hand, people in low-income groups who drank did display some tendencies that differed from the general population of drinkers. For instance, in one study as many women as men were heavy drinkers in lower income groups. Excessive drinking may also be more dangerous in lower income groups. One study found that alcohol was a major factor in the higher death rate of people, particularly men, in lower socioeconomic groups compared with those in higher groups.

Complications

Alcoholism reduces life expectancy by 10 - 12 years. Next to smoking, it is the most common preventable cause of death in America. Although studies indicate that adults who drink moderately (about one drink a day for women and two drinks a day for men) have a lower mortality rate than their nondrinking peers, their risk for untimely death increases with heavier drinking. The earlier a person begins drinking heavily, the greater their chance of developing serious illnesses later on. Once one becomes dependent on alcohol, it is very difficult to quit.

Alcohol can affect the body in so many ways that researchers have a hard time determining exactly what the consequences are from drinking. Interestingly, although heavy drinking is associated with earlier death, studies suggest it is not from a higher risk of the more common serious health problems, such as heart attack, heart failure, diabetes, lung disease, or stroke. It is well known, however, that chronic consumption leads to many problems that can increase the risk for death:

In general, people who drink regularly have a higher rate of death from injury or violence.
Alcohol overdose can lead to death. This is a particular danger for adolescents who may want to impress their friends with their ability to drink alcohol but cannot yet gauge its effects. However, alcohol overdose doesn't only occur from any one heavy drinking incident, but may also occur from a constant infusion of alcohol in the bloodstream.
Severe withdrawal and delirium tremens. Delirium tremens occurs in about 5% of alcoholics. It includes progressively severe withdrawal symptoms and altered mental states. In some cases, it can be fatal.
Frequent, heavy alcohol use directly harms many areas in the body and produce dangerous health conditions (liver damage, pancreatitis, anemia, upper gastrointestinal bleeding, nerve damage, and impotence).
Alcohol abusers who need surgery have an increased risk of postoperative complications, including infections, bleeding, insufficient heart and lung functions, and problems with wound healing. Alcohol withdrawal symptoms after surgery may impose further stress on the patient and hinder recuperation.

Although not traditionally thought of as a medical problem, a review of studies found that hangovers have significant consequences that include changes in liver function, hormonal balance, and mental functioning and an increased risk for depression and cardiac events. Hangovers can impair job performance, increasing the risk for mistakes and accidents. Interestingly, hangovers are generally more common in light-to-moderate drinkers than heavy and chronic drinkers, suggesting that binge drinking can be as threatening as chronic drinking. Any man who drinks more than five drinks or any woman who has more than three drinks is at risk for a hangover.

Alcohol plays a large role in accidents, suicide, and crime:

Alcohol plays a major role in more than half of all automobile fatalities.
Alcohol-related automobile accidents are the leading causes of death in young people.
Fewer than two drinks can impair the ability to drive. Even one drink may double the risk of injury, and more than four drinks increases the risk by 11 times.
Alcoholism is the primary diagnosis in one-quarter of all people who commit suicide.
Alcohol is implicated in 67% of all murders.

Alcoholic households are less cohesive and have more conflicts, and their members are less independent and expressive than households with nonalcoholic or recovering alcoholic parents. Domestic violence is a common consequence of alcohol abuse.

Effect on Women. Research suggests that for women, the most serious risk factor for injury from domestic violence may be a history of alcohol abuse in her male partner.

Effect on Children. Alcoholism in parents also increases the risk for violent behavior and abuse toward their children. Children of alcoholics tend to do worse academically than others, have a higher incidence of depression, anxiety, and stress and lower self-esteem than their peers. In addition to their own inherited risk for later alcoholism, many children of alcoholics have serious coping problems that may last their entire life.

Adult children of alcoholic parents are at higher risk for divorce and for psychiatric symptoms. One study concluded that the only events with greater psychological impact on children are sexual and physical abuse.

Researchers are finding common genetic factors in alcohol and nicotine addiction, which may explain, in part, why alcoholics are often smokers. Alcoholics who smoke compound their health problems. More alcoholics die from tobacco-related illnesses, such as heart disease or cancer, than from chronic liver disease, cirrhosis, or other conditions that are more directly tied to excessive drinking. Abuse of other substance is also common among alcoholics.

Alcoholic Hepatitis and Cirrhosis. Alcohol is absorbed in the small intestine and passes directly into the liver, where it becomes the preferred energy source. The liver, then, is particularly endangered by alcoholism. In the liver, alcohol converts to toxic chemicals, notably acetaldehyde, which trigger the production of immune factors called cytokines. In large amounts, these factors cause inflammation and tissue injury.

Cirrhosis is a chronic liver disease that causes damage to liver tissue, scarring of the liver (fibrosis; nodular regeneration), progressive decrease in liver function. Consequences of a failing liver include excessive fluid in the abdomen (ascites), bleeding disorders (coagulopathy), increased pressure in the blood vessels (portal hypertension), and brain function disorders (hepatic encephalopathy). Excessive alcohol use is the leading cause of cirrhosis.

Even moderate alcohol intake can produce pain in the upper right quarter of the abdomen -- a possible symptom of liver involvement. In many cases, such symptoms may be an indication of fatty liver or alcohol hepatitis, which are reversible liver conditions.

Between 10 - 20% of people who drink heavily (five or more drinks a day) develop cirrhosis, a progressive and irreversible scarring of the liver that can eventually be fatal. Alcoholic cirrhosis (also sometimes referred to as portal, Laennec’s, nutritional, or micronodular cirrhosis) is the primary cause of cirrhosis in the U.S. [For more information, see In-Depth Report #75: Cirrhosis.]

Not eating when drinking and consuming a variety of alcoholic beverages increase the risk for liver damage. Nevertheless, the amount of alcohol consumed and the patterns of drinking are only weak predictions of risk. Up to 90% of heavy drinkers do not develop advanced irreversible liver disease. Other risk factors have been identified that may increase the danger to the liver in heavy drinkers:

Obesity is a major factor for all stages of liver disease.
Women develop liver disease at lower quantities of alcohol intake than men.
Genetic factors that regulate the immune responses also play role.

Viral Hepatitis B and C. People with alcoholism tend to have lifestyles that put them at higher risk for hepatitis B and C, which are caused by viruses. Chronic forms of viral hepatitis pose risks for cirrhosis and liver cancer, and alcoholism significantly increases these risks. People with alcoholism should be immunized against hepatitis B. They may need a higher-than-normal dose of the vaccine for it to be effective. There is no vaccine for hepatitis C. [For more informaiton, see In-Depth Report #59: Hepatitis.]

Alcoholism can cause many problems in the gastrointestinal tract. Violent vomiting can produce tears in the junction between the stomach and esophagus. Alcoholism poses a high risk for diarrhea and hemorrhoids. It increases the risk for ulcers, particularly in people taking the painkillers known as nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen. It can also lead to swollen veins in the esophagus (esophagitis), called varices, which can lead to bleeding.

Click the icon to see an image of ulcer emergencies.

Alcohol can contribute to serious and chronic inflammation of the pancreas (pancreatitis) in people who are susceptible to this condition. There is some evidence of a higher risk for pancreatic cancer in people with alcoholism, although this higher risk may occur only in people who are also smokers.

Click the icon to see an image of the pancreas.

Moderate amounts (one to two drinks a day) of alcohol can improve some heart disease risk factors, such as increasing HDL (“good cholesterol”) levels. However, at this time there is no definitive proof that moderate drinking improves overall health, and the American Heart Association does not recommend drinking alcoholic beverages solely to reduce cardiovascular risk.

Excessive drinking clearly has negative effects on heart health. In fact, heart disease is one of the leading causes of death for alcoholics. Alcohol abuse increases levels of triglycerides (unhealthy fats) and increases the risks for high blood pressure, heart failure, and stroke. In addition, the extra calories in alcohol can contribute to obesity, a major risk factor for many heart problems.

Click the icon to see an image of the heart.

Alcohol abuse and dependence may increase the risk for certain type of cancers. In particular, heavy alcohol use appears to increase the risks for mouth, throat, esophageal, gastrointestinal, liver, colorectal, and breast cancers. Women who are at high risk for breast cancer should consider not drinking at all.

Pneumonia. Over time, chronic alcoholism can cause severe reductions in white blood cells, which increase the risk for community-acquired pneumonia (pneumonia acquired outside of hospitals or nursing homes). Patients who abuse alcoholism have a greater risk for developing severe pneumonia. Doctors recommend that patients with alcohol dependence should receive an annual pneumococcal pneumonia vaccination. The initial signs of pneumococcal pneumonia are high fever, cough, and stabbing chest pains. Immediately contact your doctor if you experience these symptoms.

Click the icon to see an image of pneumonia.

Severe alcoholism is associated with osteoporosis (loss of bone density), muscular deterioration, skin sores, and itching. Alcohol-dependent women seem to face a higher risk than men for damage to muscles, including muscles of the heart, from the toxic effects of alcohol.

Click the icon to see an image of osteoporosis.

Effects Sexual Function and Fertility. Alcoholism increases levels of the female hormone estrogen and reduces levels of the male hormone testosterone, factors that possibly contribute to impotence in men and infertility in women. Such changes may also be responsible for the higher risks for absent periods and abnormal uterine bleeding in women with alcoholism.

Drinking During Pregnancy and Effects on the Infant. Even moderate amounts of alcohol can have damaging effects on the developing fetus, including low birth weight and an increased risk for miscarriage. High amounts can cause fetal alcohol syndrome, a condition that can cause mental and growth retardation. Although there is no specific amount of alcohol intake, the risk of developing the syndrome is increased depending on the time of alcohol exposure during pregnancy, a patter of drinking (four or more drinks per occasion), and how often alcohol consumption occurs.

Moderate alcohol consumption may help protect the hearts of adults with type 2 diabetes. Heavy drinking however is associated with obesity, which is a risk factor for this form of diabetes. In addition, alcohol can cause hypoglycemia, a drop in blood sugar, which is especially dangerous for people with diabetes who are taking insulin. Intoxicated diabetics may not be able to recognize symptoms of hypoglycemia, a potentially hazardous condition.

Drinking too much alcohol can cause immediate mild neurologic problems in anyone, including insomnia and headache. Long-term alcohol use may even physically affect the brain. Depending on length and severity of alcohol abuse, neurologic damage may not be permanent, and abstinence nearly always leads to eventual recovery of normal mental function.

Effect on Mental Functioning. Studies have reported less blood flow in the frontal lobes of the brain, which may reflect links to deeper levels. In one study, even recent high alcohol use (within the last 3 months) was associated with some loss of verbal memory and slower reaction times. Over time, chronic alcohol abuse can impair so-called "executive functions," which include problem solving, mental flexibility, short-term memory, and attention. These problems are usually mild to moderate and can last for weeks or even years after a person quits drinking. In fact, such persistent problems in judgment are possibly one reason for the difficulty in quitting. Alcoholic patients who have co-existing psychiatric or neurologic problems are at particular risk for mental confusion and depression.

Wernicke-Korsakoff Syndrome. Wernicke-Korsakoff syndrome is a serious consequence of severe thiamin (vitamin B1) deficiency in alcoholism. Symptoms of this syndrome include severe loss of balance, confusion, and memory loss. Eventually, it can result in permanent brain damage and death. Once the syndrome develops, oral supplements have no effect, and only adequate and rapid intravenous vitamin B1 can treat this serious condition.

Peripheral Neuropathy. Vitamin B1 deficiencies can also lead to peripheral neuropathy, a condition that causes pain, tingling, and other abnormal sensations in the arms and legs.

Click the icon to see an image of the nervous system.

People with alcoholism should be sure to take vitamin and mineral supplements. Even apparently well-nourished people with alcoholism may be deficient in important nutrients. Deficiencies in vitamin B are particularly health risks in people with alcoholism. Other vitamin and mineral deficiencies, however, can also cause widespread health problems.

Folate Deficiencies. Alcohol interferes with the metabolism of folate, a very important B vitamin, called folic acid when used as a supplement. Folate deficiencies can cause severe anemia. Deficiencies during pregnancy can lead to birth defects in the infant.

Vitamin B1 Deficiencies. Many of the B vitamins are essential for nerve protection. Severe deficiencies are common in alcoholism and can have serious consequences on the central nervous system, notably peripheral neuropathy and, in very severe cases, Wernicke-Korsakoff syndrome.

The effects of many medications are strengthened by alcohol, while others are inhibited. Of particular importance is alcohol's reinforcing effect on anti-anxiety drugs, sedatives, antidepressants, and antipsychotic medications. Alcohol also interacts with many drugs used by people with diabetes. It interferes with drugs that prevent seizures or blood clotting. It increases the risk for gastrointestinal bleeding in people taking aspirin or other nonsteroidal inflammatory drugs (NSAIDs) including ibuprofen and naproxen. Chronic alcohol abusers have a particularly high risk for adverse side effects from consuming alcohol while taking certain antibiotics. These side effects include flushing, headache, nausea, and vomiting. In other words, taking almost any medication should preclude drinking alcohol.

Diagnosis

Even when people with alcoholism experience withdrawal symptoms, they nearly always deny the problem, leaving it up to co-workers, friends, or relatives to recognize the symptoms and to take the first steps toward encouraging treatment. Denial, in fact, may be an important warning signal for alcoholism.

Family members cannot always rely on a doctor to make an initial diagnosis. Although 15 - 30% of people who are hospitalized have alcoholism or alcohol dependence, doctors often fail to screen for the problem. In addition, doctors themselves often do not recognize the symptoms. Even when doctors identify an alcohol problem, however, they are frequently reluctant to confront the patient with a diagnosis that might lead to treatment for addiction.

A doctor who suspects alcohol abuse should ask the patient questions about current and past drinking habits to distinguish moderate from heavy, or hazardous, drinking. Screening tests for alcohol problems in older people should account for possible medical problems or medications that might place them at higher risk for hazardous drinking than younger individuals.

A number of short screening tests are available, which a person can even take on their own. Because people with alcoholism often deny their problem or otherwise attempt to hide it, the tests are designed to elicit answers related to problems associated with drinking rather than the amount of liquor consumed or other specific drinking habits.

CAGE Test. The CAGE test is an acronym for the following questions and is the quickest test:

Attempts to CUT (C) down on drinking
ANNOYANCE (A) with criticisms about drinking
GUILT (G) about drinking
Use of alcohol as an EYE-OPENER (E) in the morning

This test and another called the Self-Administered Alcoholism Screening Test (SAAST) appear to be most useful in detecting possible alcoholism in white, middle-aged males. They are not very accurate for identifying alcohol abuse in older people, white women, and African-Americans and Mexican Americans.

T-ACE Test. The T-ACE test is a four-question test that appears to be quite accurate in identifying alcoholism in both men and women. It asks the following questions:

Does it TAKE (T) more than three drinks to make you feel high?
Have you ever been ANNOYED (A) by people's criticism of your drinking?
Are you trying to CUT DOWN (C) on drinking?
Have you ever used alcohol as an EYE OPENER (E) in the morning?

A positive response to two of these four questions is considered to indicate possible alcohol abuse or dependence.

AUDIT Test. A more effective and important test for most people may be the Alcohol Use Disorders Identification Test (AUDIT), which is the only test specifically designed to identify hazardous or harmful drinking. It asks three questions about amount and frequency of drinking, three questions about alcohol dependence, and four questions about problems related to alcohol consumption.

A Single-Question. One simple question may be as sensitive as the CAGE or AUDIT: "When was the last time you had more than five drinks (for men) or four drinks (for women) in one day?" An answer of "within 3 months" accurately identified about half of people who were problem drinkers. Problem drinking is defined as hazardous drinking within the last month or some alcohol-use disorder during the past year.

Other Screening Tests. Other short screening tests are the Michigan Alcoholism Screening Test (MAST) and the Alcohol Dependence Scale (ADS).

Some symptoms of alcoholism may be attributed to other disorders, particularly in the elderly, where symptoms of confusion, memory loss, or falling may be attributed to the aging process alone. Heavy drinkers may be more likely to complain to their doctors about so-called somatization symptoms, which are vague ailments, such as joint pain, intestinal problems, or general weakness, that have no identifiable physical cause. Such complaints should signal the doctor to follow-up with screening tests for alcoholism.

Alcoholism is particularly less likely to be recognized in elderly women. In fact, only 1% of older women who need treatment for alcoholism are diagnosed accurately and treated appropriately. Instead, they are often diagnosed with depression and may even be prescribed anti-anxiety drugs or antidepressants that can have dangerous interactions with alcohol.

Physical Examination. A physical examination and other tests should be performed to uncover any related medical problems.

Laboratory Tests. Tests for alcohol levels in the blood are not useful for diagnosing alcoholism because they reflect consumption at only one point in time and not long-term usage. Certain blood tests, however, may provide biologic markers that suggest medical problems associated with alcoholism or indications of alcohol abuse:

Carbohydrate-deficient transferrin (CDT). This compound is a marker for heavy drinking and can be helpful in monitoring patients for progress towards abstinence.
Gamma-glutamyltransferase (GGT). This liver enzyme is very sensitive to alcohol and can be elevated after moderate alcohol intake and in chronic alcoholism.
Aspartate (AST) and alanine aminotransaminases (ALT). These are liver enzymes and are markers for liver damage.
Testosterone. Male hormone levels in men with alcoholism may be low. (Such results sometimes persuade men with alcoholism to seek help.)
Mean corpuscular volume (MCV). This blood test measures the size of red blood cells, which increase with alcohol use over time.

Treatment for Alcoholism

Once a diagnosis of alcoholism is made, the next major step is getting the patient to seek treatment. The main reasons alcoholics do not seek treatment are:

Lack of confidence in successful therapies
Denial of their own alcoholism
Social stigma attached to the condition and its treatment

The alcoholic patient and everyone involved should fully understand that alcoholism is a disease. Furthermore, the responses to this disease (need, craving, fear of withdrawal) are not character flaws but symptoms, just as pain or discomfort are symptoms of other illnesses. They should also realize that treatment is difficult and sometimes painful, just as are treatments for other life-threatening diseases, such as cancer, but that treatment is the only hope for a cure.

Interventions by family members, employers, and therapists can be very effective in motivating a person to quit and in reducing drinking over the short term. Even brief interventions from a primary care doctor and self-help information can be helpful in reducing harmful drinking. Studies report, however, that only regular follow-up and reinforcement will sustain quit rates and possibly even improve survival rates.

Personal Intervention Meetings. The best approaches for motivating a patient to seek treatment are interventional group meetings between people with alcoholism and their friends and family members who have been affected by the alcoholic behavior. Using this approach, each person affected offers a compassionate but direct and honest report describing specifically how they have been hurt by their loved one's alcoholism. The family and friends should express their affection for the patient and their intentions for supporting the patient through recovery, but they must strongly and consistently demand that the patient seek treatment. Children may even be involved in this process, depending on their level of maturity and ability to handle the situation.

Employer Intervention. Employers can be particularly effective. Their approach should also be compassionate but strong, threatening the employee with loss of employment if they do not seek help. Some large companies provide access to inexpensive or free treatment programs for their workers. Studies suggest that such interventions are effective at helping the worker at least to cut back on drinking.

The ideal goals of long-term treatment by many doctors and organizations such as Alcoholics Anonymous (AA) are total abstinence. Patients who secure total abstinence have better survival rates, mental health, and marriages, and they are more responsible parents and employees than those who continue to drink or relapse. To achieve this, the patient aims to avoid high-risk situations and replace the addictive patterns with satisfying, time-filling behaviors.

Because abstinence is so difficult to attain, however, many professionals choose to treat alcoholism as a chronic disease. In other words, patients should expect and accept relapse but should aim for as long a remission period as possible. Even merely reducing alcohol intake can lower the risk for alcohol-related medical problems.

AA and other alcoholic treatment groups are greatly worried by treatment approaches that do not aim for strict abstinence, however. Many people with alcoholism are eager for any excuse to start drinking again. There is also no way to determine which people can stop after one drink and which ones cannot.

Evidence strongly suggests that seeking total abstinence and avoiding high-risk situations are the optimal goal for people with alcoholism.

A number of treatment options now exist for alcoholism. It is first important to determine whether inpatient or outpatient care would best benefit the individual. A variety of treatment options exist that do not require overnight stay in a hospital. Structured programs exist that involve anywhere from a couple of hours a day for several days a week to 20 or more hours per week (sometimes called partial hospitalization) of monitoring. Withdrawal and subsequent abstinence monitoring using outpatient visits to a doctor is occasionally tried for select, low-risk patients.

Inpatient care may also be performed in a general or psychiatric hospital or in a center dedicated to treatment of alcohol and other substance abuse. Factors that indicate a need for this type of treatment include:

Coexisting medical or psychiatric disorder
Delirium tremens
Potential harm to selves or others
Failure to respond to conservative treatments
Disruptive home environment

A typical inpatient regimen may include the following stages:

A physical and psychiatric work-up for any physical or mental disorders
Detoxification -- this phase involves initiating abstinence, managing withdrawal symptoms and complications, and ensuring that the patient remains in treatment
On-going treatment with medications in some cases
Psychotherapy, usually cognitive behavioral therapy
An introduction to Alcoholics Anonymous

Some -- but not all -- studies have reported better success rates with inpatient treatment of patients with alcoholism. However, newer studies strongly suggest that alcoholism can be effectively treated in a doctor’s office.

The new approach to outpatient treatment uses “medical management” -- a disease management approach that is used for chronic illnesses such as diabetes. With medical management, patients receive regular 20-minute sessions with a health care provider. The provider monitors the patient’s medical condition, medication, and alcohol consumption.

A medical management approach generally involves one or both of the following:

Drug treatment with naltrexone (ReVia, Vivitrol)
Behavioral counseling with a therapy technique called combined behavioral intervention (CBI)

Outpatient Treatment Options. People with mild-to-moderate withdrawal symptoms are usually treated as outpatients. Treatments are similar to those in inpatient situations and include:

Psychotherapy or counseling
Medications that target brain chemicals involved in addiction
Social support groups such as Alcoholics Anonymous
Cognitive therapies
Quitting smoking (smoking interferes with the brain’s recovery from alcoholism)
Involvement of family and other significant people in patient's life

After-Care and Work Therapy. After-care employs services that help alcoholics maintain sobriety. For example, in some cities, sober-living houses provide residences for people who are trying to stay sober. They do not offer formal treatment services, but the people living there offer each other support and maintain an abstinent environment. One study reported that work therapy improved the outcome for homeless veterans who were being treated for substance abuse.

About 25% of people are continuously abstinent following treatment, and another 10% use alcohol moderately and without problems. Most studies strongly suggest that intensive and prolonged treatment is important for successful recovery, whether the patient is treated within or outside a treatment center.

Certain factors play a role in success or failure. Patients from low-income groups tend to have worse results in general. Their difficulties are often intensified by lack of insurance, low self-esteem, and minimal social support.

Severe alcoholism is often complicated by the presence of serious medical illnesses. People with alcoholism should try at least to maintain a healthy diet and take vitamin supplements. Such deficiencies are a major cause of health problems in people with alcoholism. Women are particularly endangered.

A program called integrated outpatient treatment (IOT) may be specifically helpful for medically ill alcoholics. The patient visits a clinic once a month and receives both intensive alcohol treatment and a physical check-up, which includes tracking factors, such as liver function, that are affected by drinking.

Treatment for patients with both alcoholism and mental illness is particularly difficult. The greater the psychiatric distress a person is experiencing, the more the person is tempted to drink, particularly in negative situations.

There has been some concern that self-help programs, such as Alcoholics Anonymous (AA), are not effective for patients with dual diagnoses of mental illness and alcoholism, because the focus of the organization is on addiction, not psychiatric problems. Studies, however, have reported that they are also effective in many of these patients. (AA may not be as helpful for people with schizophrenia and schizoaffective disorder.) In one study, individuals with a dual diagnosis achieved better abstinence rates after being treated only for alcoholism compared to patients treated for the mental disorder as well. (Cognitive-behavioral therapy was used for both groups.)

Newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are proving to be very useful complements to AA or counseling sessions. Anti-anxiety medications are also available for people with anxiety. People with alcoholism and more severe problems such as schizophrenia or severe bipolar disorder may require other types of medications.

Treatment for Alcohol Withdrawal

When a person with alcoholism stops drinking, withdrawal symptoms begin within 6 - 48 hours and peak about 24 - 35 hours after the last drink. During this period, the inhibition of brain activity caused by alcohol is abruptly reversed. Stress hormones are overproduced, and the central nervous system becomes overexcited. Common symptoms include:

Anxiety
Irritability
Agitation
Insomnia

Additional symptoms may include:

Extremely aggressive behavior
Fever
Rapid heartbeat
Changes in blood pressure (either higher or lower)
Mental disturbances
Seizures occur in about 10% of adults during withdrawal. In about 60% of these patients, the seizures are multiple. The time between the first and last seizure is usually 6 hours or less.
Delirium tremens (DTs) are withdrawal symptoms that become progressively severe and include altered mental states (hallucinations, confusion, severe agitation) or generalized seizures. DTs are potentially fatal. They develop in up to 5% of alcoholic patients, usually 2 - 4 days after the last drink, although it may take 2 or more days to peak.

It is not clear if older people with alcoholism are at higher risk for more severe symptoms than younger patients. However, several studies have indicated that they may suffer more complications during withdrawal, including delirium, falls, and a decreased ability to perform normal activities.

Upon entering a hospital due to alcohol withdrawal, patients should be given a physical examination for any injuries or medical conditions. They should be treated, if possible, for any potentially serious problems, such as high blood pressure, anemia, liver damage, or irregular heartbeat.

The immediate goal of treatment is to calm the patient as quickly as possible. Patients should be observed for at least 2 hours to determine the severity of withdrawal symptoms. Doctors may use assessment tests, such as the Clinical Institute Withdrawal Assessment (CIWA) scale, to help determine treatment and whether the symptoms will progress in severity.

About 95% of people have mild-to-moderate withdrawal symptoms, including agitation, trembling, disturbed sleep, and lack of appetite. In 15 - 20% of people with moderate symptoms, brief seizures and hallucinations may occur, but they do not progress to full-blown delirium tremens. Such patients often can be treated as outpatients. After being examined and observed, the patient is usually sent home with a 4-day supply of anti-anxiety medication, scheduled for follow-up and rehabilitation, and advised to return to the emergency room if withdrawal symptoms increase in severity. If possible, a family member or friend should support the patient through the next few days of withdrawal.

Benzodiazepines. Anti-anxiety drugs known as benzodiazepines inhibit nerve-cell excitability in the brain and are considered to be the treatment of choice. They relieve withdrawal symptoms, help prevent progression to delirium tremens, and reduce the risk for seizures. Long-acting drugs, such as chlordiazepoxide (Libritabs, Librium), oxazepam (Serax), and halazepam (Paxipam) are preferred. They pose less risk for abuse than the shorter-acting drugs, which include diazepam (Valium), alprazolam (Xanax), and lorazepam (Ativan).

Assessing symptoms frequently and administering benzodiazepine doses as needed (instead of giving to a fixed dose at regular intervals) may reduce the incidence of withdrawal symptoms and other adverse events, including delirium, seizures, and transfer to the intensive care unit.

Some doctors question the use of any anti-anxiety medication for mild withdrawal symptoms, since these drugs are subject to abuse. Others believe that repeated withdrawal episodes, even mild forms, that are inadequately treated may result in increasingly severe and frequent seizures with possible brain damage. In any case, benzodiazepines are usually not prescribed for more than 2 weeks or administered for more than 3 nights per week. Problems with benzodiazepines include:

Side Effects. Common side effects of benzodiazepines are daytime drowsiness and a hung-over feeling. In rare cases, they actually cause agitation. Respiratory problems may be worsened. The drugs stimulate eating and can cause weight gain. Benzodiazepines can interact with certain drugs, including cimetidine (Tagamet), antihistamines, and oral contraceptives. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses are serious, although rarely fatal. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people. Benzodiazepines are associated with birth defects and should not be used by pregnant women or nursing mothers.
Loss of Effectiveness and Dependence. The primary problem with these drugs is their loss of effectiveness over time with continued use at the same dosage. As a result, patients may increase their dosage level to prevent anxiety. Patients then can become dependent. In fact, some evidence suggests that people with alcoholism, or even a family history of alcoholism, may be more susceptible to benzodiazepine abuse than nonalcoholics. This is a common danger and can occur after as short a time as 3 months. (These drugs do not cause euphoria, a so-called "high," so such drugs are not addictive in the same way narcotics are.)
Withdrawal Symptoms. People who discontinue benzodiazepines after taking them for even 4 weeks can experience mild rebound symptoms. The longer the drugs are taken and the higher the dose, the more severe the symptoms. They include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience withdrawal symptoms, including stomach distress, sweating, and insomnia, that can last from 1 - 3 weeks. Sleep changes, in fact, can persist or months or years after quitting and may be a major factor in relapse.

Antiseizure Medications. Antiseizure drugs, such as carbamazepine (Tegretol) or divalproex sodium (Depakote), may be useful for reducing the requirements of a benzodiazepine. When used by themselves, however, they do not appear to reduce seizures or delirium associated with withdrawal.

Other Supportive Drugs. Beta-blockers, such as propranolol (Inderal) and atenolol (Tenormin), are sometimes used in combination with benzodiazepines. They slow heart rate and reduce tremors. They may also reduce cravings.

Note on Treating Alcohol Withdrawal with Alcohol. Some medical centers give patients alcohol to help with withdrawal. Experts do not recommend this approach. There is no evidence that this approach is safe or effective, while there is substantial evidence on the safety and effectiveness of benzodiazepines.

Treating Delirium Tremens. People with symptoms of delirium tremens must be treated immediately. Untreated delirium tremens has a fatality rate that can be as high as 20%. Treatment usually involves intravenous anti-anxiety medications. It is extremely important that fluids be administered. Restraints may be necessary to prevent injury to the patient or to others.

Treating Seizures. Seizures are usually self-limited and treated with a benzodiazepine. Intravenous phenytoin (Dilantin) along with a benzodiazepine may be used in patients who have a history of seizures, who have epilepsy, or in those with ongoing seizures. Because phenytoin may lower blood pressure, the patient's heart should be monitored during treatment. Chlormethiazole, a derivative of vitamin B1, is used in Europe for reducing agitation and seizures.

Psychosis. For hallucinations or extremely aggressive behavior, antipsychotic drugs, particularly haloperidol (Haldol), may be administered. Korsakoff's psychosis (Wernicke-Korsakoff syndrome) is caused by severe vitamin B1 (thiamine) deficiencies, which cannot be replaced orally. Rapid and immediate injection of the B vitamin thiamin is necessary.

Therapy

Standard forms of therapy for alcoholism include:

Cognitive-behavioral therapy
Combined behavioral intervention
Interactional group psychotherapy based on the Alcoholics Anonymous (AA) 12-step program

Comparison studies have reported that these approaches are equally effective when the program is competently administered. Specific people may do better with one program than another. One study, for example, examined the differences in success rates on type 1 or type 2 alcoholics:

People in the type 1 group did well with the 12-step approach. They did not do as well with cognitive-behavioral therapy. (Type 1 individuals become alcoholic at a later age, have less severe symptoms or fewer psychiatric problems, and have a better outlook on life than those classified as type 2. They are more likely to be women.)
The people in the type 2 group tended to do better with cognitive-behavioral therapy. (Type 2 people are more likely to be male, become alcoholic at an early age, have a high family risk for alcoholism, have more severe symptoms, and have a negative outlook on life.)

This difference in response to the two forms of treatment held up after 2 years. Other studies have also reported that people with fewer psychiatric problems do best with the AA approach.

AA, founded in 1935, is an excellent example of interactional group psychotherapy and remains the most well-known program for helping people with alcoholism. It offers a very strong support network using group meetings open 7 days a week in locations all over the world. A buddy system, group understanding of alcoholism, and forgiveness for relapses are AA's standard methods for building self-worth and alleviating feelings of isolation.

AA's 12-step approach to recovery includes a spiritual component that might deter people who lack religious convictions. Prayer and meditation, however, have been known to be of great value in the healing process of many diseases, even in people with no particular religious assignation. AA emphasizes that the "higher power" component of its program need not refer to any specific belief system. Associated membership programs, Al-Anon and Alateen, offer help for family members and friends.

We admit we were powerless over alcohol -- that our lives have become unmanageable.
We have come to believe that a Power greater than ourselves could restore us to sanity.
We have made a decision to turn our will and our lives over to the care of God, as we understand what this Power is.
We have made a searching and fearless moral inventory of ourselves.
We have admitted to God, to ourselves and to another human being the exact nature of our wrongs.
We are entirely ready to have God remove all these defects of character.
We have humbly asked God to remove our shortcomings.
We have made a list of all persons we had harmed and have become willing to make amends to them all.
We have made direct amends to such people wherever possible, except when to do so would injure them or others.
We have continued to take personal inventory and when we were wrong promptly admitted it.
We have sought through prayer and meditation to improve our conscious contact with God as we understand what this higher Power is, praying only for knowledge of God's will for us and the power to carry that out.
Having had a spiritual awakening as the result of these steps, we have tried to carry this message to alcoholics and to practice these principles in all our affairs.

Cognitive-behavioral therapy (CBT) uses a structured teaching approach and may be better than AA for people with severe alcoholism. Patients are given instruction and homework assignments intended to improve their ability to cope with basic living situations, control their behavior, and change the way they think about drinking. The following are examples of approaches:

Patients might write a history of their drinking experiences and describe what they consider to be risky situations.
They are then assigned activities to help them cope when exposed to "cues" (places or circumstances that trigger their desire to drink).
Patients may also be given tasks that are designed to replace drinking. An interesting and successful example of such a program was one that enlisted patients in a softball team. This gave them the opportunity to practice coping skills, develop supportive relationships, and engage in healthy alternative activities.

CBT may be especially effective when used in combination with opioid antagonists, such as naltrexone. CBT that addresses alcoholism and depression also may be an important treatment for patients with both conditions.

Combined behavioral intervention (CBI) is a new form of therapy that uses special counseling techniques to help motivate people with alcoholism to change their drinking behavior. CBI combines elements from other psychotherapy treatments such as cognitive behavioral therapy, motivational enhancement therapy, and 12-step programs. Patients are taught how to cope with drinking triggers. Patients also learn strategies for refusing alcohol so that they can achieve and maintain abstinence. In a 2006 study in the Journal of the American Medical Association, CBI -- combined with regular doctor’s office visits (medical management) -- worked as well as naltrexone in successfully treating alcoholism.

Partners of people with alcoholism can also benefit greatly from behavioral approaches that help them cope with their mate. Children of an alcoholic mother or father may do better if both parents participate in couples-based therapy, rather than just treating the parent with alcoholism.

Nearly all patients who are alcohol dependent suffer from insomnia and sleep problems, which can last months to years after abstinence. Sleep disturbances may even be important factors in relapse. Available therapies include sleep hygiene, bright light therapy, meditation, relaxation methods, and other nondrug approaches. Many medications for inducing sleep are not recommended in people with alcoholism. [For more information, see In-Depth Report #27: Insomnia.]

Some people try alternative methods, such as acupuncture or hypnosis. Such approaches are not harmful. In one study, acupuncture reduced the desire for alcohol in nearly half of people, although it was not significantly more helpful than conventional treatments.

Medications

In the U.S., three drugs are specifically approved to treat alcohol dependence:

Naltrexone (ReVia, Vivitrol)
Acamprosate (Campral)
Disulfiram (Antabuse)

Naltrexone and acamprosate are categorized as anticraving drugs. Disulfiram is an aversion drug. Other types of medications, such as antidepressants, may also be used to treat patients with alcoholism.

Anticraving drugs are opioid antagonists. These drugs reduce the intoxicating effects of alcohol and the urge to drink

Naltrexone. Naltrexone (ReVia, Vivitrol) is approved for the treatment of alcoholism and helps reduce alcohol dependence in the short term for people with low-to-moderate alcohol dependency. ReVia is a pill that is taken daily by mouth. In 2006, the FDA approved Vivitrol, a once-a-month injectable form of naltrexone.

Naltrexone is usually prescribed along with psychotherapy. The most common side effect is nausea, which is usually mild and temporary. High doses can cause liver damage. The drug should not be given to anyone who has used narcotics within 7 - 10 days. For ReVia, it is important that patients take the pill on a daily basis. Because many patients have difficulty sticking to this daily regimen, a monthly injection of Vivitrol may be an easier option.

Naltrexone does not work in all patients. Some studies suggest that people with a specific genetic variant may respond better to the drug than those without the gene. The gene regulates receptors that affect the response to opioids. A 2005 study indicated that naltrexone works best for patients who have a family history of alcoholism, began drinking at an early age, and abuse other drugs.

Research is being conducted on the effects of combining naltrexone with acamprosate (Campral), particularly for individuals who have not responded to single drug treatment. In a 2006 study in the Journal of the American Medical Association that examined various outpatient drug and behavioral treatments, naltrexone worked as well as psychotherapy in preventing relapse to heavy drinking for patients who had recently abstained from alcohol. However, the study showed no benefit for acamprosate either when combined with naltrexone or used alone.

Acamprosate. Acamprosate (Campral) is the newest drug to be approved for treatment of alcoholism. Acamprosate calms the brain and reduces cravings by inhibiting the transmission of the neurotransmitter gamma aminobutyric acid (GABA). Studies indicate that it reduces the frequency of drinking and, in concert with psychotherapy, improves quality of life even in patients with severe alcohol dependence. One study reported that 60% of patients remained abstinent for 12 weeks, and in another 43% were still abstinent after nearly a year. The drug may cause occasional diarrhea and headache. It also can impair certain memory functions but does not alter short-term working memory or mood. People with kidney problems should use acamprosate cautiously. For some patients, combination therapy with naltrexone or disulfiram may provide greater benefit than acamprosate alone.

Disulfiram. Some drugs have properties that interact with alcohol to produce distressing side effects. Disulfiram (Antabuse) causes flushing, headache, nausea, and vomiting if a person drinks alcohol while taking the drug. The symptoms can be triggered after drinking half a glass of wine or half a shot of liquor and may last from half an hour to 2 hours, depending on dosage of the drug and the amount of alcohol consumed. One dose of disulfiram is usually effective for 1 - 2 weeks. Overdose can be dangerous, causing low blood pressure, chest pain, shortness of breath, and even death. The drug is more effective if patients have family or social support, including AA "buddies," who are close by and vigilant to ensure that they take it.

Topiramate. Topiramate (Topamax) is an anti-seizure drug used to treat epilepsy. It also helps control impulsivity. Studies indicate it may be a promising treatment for alcohol dependence. In one well-designed study, patients who took topirimate had fewer heavy drinking days, fewer drinks per day, and more continuous days of abstinence than patients who received placebo. Side effects included burning and itching skin sensations, change in taste sensation, loss of appetite, and difficulty concentrating.

Resources

www.niaaa.nih.gov -- National Institute on Alcohol Abuse and Alcoholism
www.samhsa.gov -- Substance Abuse and Mental Health Services Administration
www.ncadi.samhsa.gov -- National Clearinghouse for Alcohol and Drug Information
www.aca-usa.org -- American Council on Alcoholism
www.ncadd.org -- National Council on Alcoholism
www.alcoholics-anonymous.org -- Alcoholics Anonymous
www.al-anon-alateen.org -- Al-Anon Family Group Headquarters
www.nofas.org -- National Organization on Fetal Alcohol Syndrome

References

Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17.

Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. CMAJ. 2005 Mar 1;172(5 Suppl):S1-S21.

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Review Date:
12/28/2007
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.

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