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Partner Yoga Book: Contact - The Yoga of Relationship

FitSugar — Sat, 30 Aug 2008 03:00:00 -0700

I find practicing yoga regularly helps keep me feeling centered, both physically and mentally. But that doesn't mean you need to do yoga solo. Partner yoga can be often be twice as fun and more enriching. The book Contact: The Yoga of Relationship ($26) is a great way to learn how to make many poses work for two people.

This book is filled with gorgeous full size black and white photos of really creative partner poses, for both the beginner and the experienced yogi alike. The book is organized around seven points of contact yoga: trust, passion, commitment, love, communication, vision, and union. As you peruse through the pages, you'll see that there are several unique postures to try that are associated with each point. Trying these poses out with a partner is sure to strengthen your connection with that person, and leave you both smiling.

To see inside this book, read more.

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Fit's Tips: If you're interested in checking out other Partner Yoga books, these are a few of my faves: The Joy of Partnered Yoga, Yoga For Partners, and the DVD Together - The Art of Partnered Yoga.

Contact: The Yoga of Relationship

FitSugar — Sun, 27 Jul 2008 06:02:18 -0700

Interested in a unique Partner Yoga book? This one is both gorgeous and informative. Here are some examples of pages.

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Chronic fatigue syndrome

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Causes

Four out of five people with chronic fatigue syndrome (CFS) are infected with an enterovirus -- one of the viruses that cause respiratory and gastrointestinal infections -- compared with only one out of five healthy people. The virus might be a trigger for CFS, although research has not yet confirmed a cause-and-effect relationship.

Diagnosis

According to new guidelines, symptoms that suggest a diagnosis of CFS include disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition. Other symptoms may include difficulty concentrating or sleeping, dizziness, headaches, muscle or joint pain, sore throat, and palpitations. Doctors should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children.
Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation.

Treatment

According to one study, people with CFS who used cognitive behavioral therapy (CBT) had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use the therapy.
A 2007 study found that taking two 10 milligram doses of methylphenidate (Ritalin) each day works much better than placebo at relieving fatigue and concentration problems in people with CFS.

Introduction

Chronic fatigue syndrome (CFS), sometimes called immune dysfunction syndrome or myalgic encephalomyelitis (in Europe), is not a new disorder. In the 19th century the term neurasthenia, or nervous exhaustion, was applied to symptoms resembling CFS. In the 1930s through the 1950s, outbreaks of disease marked by prolonged fatigue were reported in the United States and many other countries. Beginning in the early- to mid-1980s, interest in chronic fatigue syndrome was revived by reports in America and other countries of various outbreaks of long-term debilitating fatigue.

Unexplained chronic fatigue describes fatigue that lasts for more than 6 months, impairs normal activities, and has no identifiable medical or psychological problems to account for it. In addition to fatigue, people may complain of other problems, such as difficulty with memory or concentration, headaches, or sore muscles or joints.

The symptoms of CFS may be categorized as follows:

Chronic fatigue syndrome (CFS). A number of criteria must be met in order for a patient's symptoms to be described as CFS. Six million patient visits are made each year because of fatigue, although only a very small percentage of these visits can be attributed to actual chronic fatigue syndrome.
Idiopathic chronic fatigue. If the symptoms do not meet the criteria for CFS, the condition is referred to as idiopathic chronic fatigue, meaning the cause is unknown.

Although the exact causes of CFS are not known, researchers think infection, genetics, hormonal imbalances, and chemical toxins play roles in different patients.

Risk Factors

In studies of large patient groups, 15 - 27% of people complain of long-term fatigue, but the majority of this fatigue can be explained by other medical or psychological problems. According to surveys, chronic fatigue syndrome (CFS) itself affects more than four out of every 1,000 Americans.

CFS occurs in both sexes, at all ages, and in all racial and ethnic groups. The Centers for Disease Control and Prevention estimates 1 million people in the U.S. have the disease, but only 20% of people with CFS may be properly diagnosed. Nevertheless, the true prevalence of CFS is very difficult to determine, since an accurate diagnosis is hard to obtain.

People ages 40 - 50 most often experience chronic fatigue. Studies have found that four out of five people with CFS are women, although a woman's symptoms do not appear to be more severe symptoms than those of men with the disorder.

Children and adolescents are not immune to CFS. Most studies indicate that girls are more likely than boys to develop CFS, although one study found the incidence of the syndrome to be equal in children among the genders.

The link between psychological disorders and chronic fatigue syndrome is problematic because so many of the symptoms overlap. The rates of depression are very high in CFS patients, possibly higher than in patients with other conditions (notably fibromyalgia and multiple chemical sensitivity).

Studies report that most children and adolescents with CFS have psychiatric disorders. Psychological factors during childhood may increase susceptibility for later CFS, although these factors are not consistent. Studies have not found any consistent association between emotional or personality disorders and CFS to explain any causal role. Some psychological factors may, however, serve as a risk factor for CFS.

Depression, in any case, is very common in the general population. It affects up to one-fifth of all Americans at some point in their lives, and most depressed people feel fatigued.

There is some evidence that stress may be a trigger for CFS in people genetically at risk for the disease.

A number of conditions overlap or coexist with chronic fatigue syndrome and have similar symptoms. Patients with CFS may also have a diagnosis of fibromyalgia, multiple chemical sensitivity, or both. It is not clear whether these conditions or others are risk factors for CFS, are direct causes, have common causes, or have no relationship at all with CFS.

Fibromyalgia. Fibromyalgia causes prolonged fatigue and widespread muscle aches. It is the disease most often confused with CFS. The two conditions also commonly appear together. In fact, many experts believe fibromyalgia is simply another variant of chronic fatigue syndrome or different manifestations of the same disease. CFS patients experience severe fatigue, whereas fibromyalgia patients experience more pain. One hypothesis proposes that the connection between the two conditions may be found in central sensitization, which is thought to cause fibromyalgia and may also cause CFS.

A characteristic feature of fibromyalgia is the existence of at least 11 distinct sites of deep muscle tenderness that hurt when touched firmly. The sites often include the following:

The side of the neck
The top of the shoulder blade
The outside of the upper buttock and hip joint
The inside of the knee

Some patients with CFS exhibit similar tender pressure points. Recurrent sore throat, headache, low fever, and depression are also common symptoms of fibromyalgia. Like CFS, fibromyalgia is chronic and not curable.

Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a term now used to describe a condition in which certain chemicals are believed to cause symptoms similar to CFS in some people. It has also been observed in people with CFS. The following proposed criteria can help recognize people with MCS:

The symptoms are reproducible with repeated exposure to a chemical. (These are often common chemicals found in popular products, such as perfumes, fabric softeners, and air fresheners.)
The condition is chronic.
Symptoms can be produced by exposure to the chemical at levels lower than previously or commonly tolerated.
The symptoms improve when the chemical is removed.
Symptoms can be triggered by multiple substances that are chemically unrelated.
Symptoms involve multiple organ systems.

Still, as with CFS and fibromyalgia, there is uncertainty as to whether MCS is an actual medical condition or is psychologically based. In one study, for example, CFS patients who believed their problem was chemically triggered were exposed to either an active chemical or a placebo (an inactive substance). Both groups reported symptoms, including those exposed only to the placebo. It should be noted that everyone is exposed to many chemicals on a daily basis, and it is very difficult to determine whether chemicals are responsible for specific symptoms.

Post-ADD. Young adults who had attention deficit disorder as children can flip from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping at any time or anywhere). These patients respond well to psychostimulant medications.

Eating Disorders. Eating disorders, notably bulimia and anorexia, have been observed in patients with CFS. The conditions often have overlapping risk factors, although it is unclear whether there is a causal relationship.

Other Conditions that Commonly Coexist With CFS. A number of other conditions also often coexist with CFS and, in fact, occur at higher-than-average rates among CFS patients:

Chronic headaches
Cognitive problems such as difficulty concentrating, impaired memory, and symptoms of attention deficit disorder
Interstitial cystitis
Irritable bowel syndrome
Sleep problems
Temporomandibular disorder (TMD)

Causes

Theories abound about the causes of chronic fatigue syndrome. Indeed, no primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition.

Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:

Genetic factors
Brain abnormalities
A hyper-reactive immune system
Viral or other infectious agents
Psychiatric or emotional conditions

For example, the majority of patients report some preceding moderate-to-serious physical illness (such as a chronic viral infection) or emotional event (like an episode of depression). Some experts theorize that such events, alone or in combination, may interact with certain neurologic and genetic abnormalities to trigger the event.

Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific brain or nervous system problem that experts can point to with assurance. Research indicates that CFS is more common among identical twins (who share the same genes) than fraternal twins (who share only some genes). Inheritance, then, may play a role in roughly 30 - 50% of cases, similar to the influence thought to occur in depression or alcoholism, although specific genes have not yet been identified.

New evidence suggests genes involved in the body's response to stress may play key roles in CFS. A series of 14 articles published in 2006 linked CFS with genes involved in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. The researchers were able to locate a common variation of DNA sequences that predicted CFS with 76% accuracy. The genes control response to trauma, injury, and other stressful events. Nevertheless, the researchers were unable to find genetic markers of CFS or to determine how the genetic variations influenced symptoms.

In 2005, English researchers found that people with CFS are more likely than people without CFS to have human leukocyte antigen (HLA) class II alleles, variations that produce antibodies to certain immune factors. Another British study of people with CFS found alterations in 16 specific genes involved with immune function, communication between cells, and transfer of energy to cells.

Abnormal levels of certain chemicals regulated in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, response to stress, and depression. Of particular interest to researchers are the following chemicals and other factors controlled by the HPA axis:

Changes in Important Neurotransmitters. Research has reported that some patients with CFS have abnormally high levels of serotonin, a neurotransmitter (chemical messenger in the brain). Such elevated levels in the brain are associated with fatigue. Studies also suggest that deficiencies of dopamine, an important neurotransmitter associated with feelings of reward, may play a role in CFS. Imbalances between norepinephrine and dopamine have been identified in certain CFS patients in several studies. Unfortunately, routine clinical testing for such chemical imbalances is cost-prohibitive.
Stress Hormone Deficiencies. A number of studies on CFS patients have observed lower levels of cortisol, a stress hormone produced in the adrenal glands. Cortisol is a precursor of dehydroepiandrosterone (DHEA), a weak male hormone that may also be important in CFS. Deficiencies may be the reason why CFS patients have an impaired and weaker response to psychological or physical stresses, such as infection or exercise. (Administering replacement cortisol improves symptoms only in some patients, indicating other factors are involved.)
Disturbed Circadian Rhythms. Evidence suggests that, in certain patients, CFS is a disorder of the sleep-wake cycle, which is regulated by the so-called circadian clock, a nerve cluster in the hypothalamus-pituitary-adrenal (HPA) axis. Some mentally or physically stressful event, such as a viral infection, may disrupt natural circadian rhythms, and an inability to reset these rhythms results in a perpetual cycle of sleep disturbances. Medications that improve sleep can be very helpful for certain patients with CFS.

However, it is still not clear whether any of these changes are causes of chronic fatigue syndrome, or merely findings in some patients.

Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases.

Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, subtypes of viral-related and non-viral CFS may both exist.

Viruses. The theory that CFS has a viral cause is not based on hard evidence, but on various observations that suggest an association, such as the following:

CFS patients typically have elevated levels of antibodies to many organisms that cause fatigue and other CFS symptoms. Such organisms include those that cause Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLV), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus. Many of these infectious agents are very common, however, and none has emerged as a significant cause of CFS.
In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition.
In the U.S., there have been reports of cluster outbreaks of CFS occurring within the same household, workplace, and community (but most have not been confirmed by the Centers for Disease Control and Prevention).
One study found that four out of five people with CFS are infected with an enterovirus -- one of the viruses that causes respiratory and gastrointestinal infections -- compared to only one out of five healthy people. The virus could be a trigger for CFS, although research has not confirmed a cause-and-effect relationship.

Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS.

Evidence suggesting that some CFS cases may not be due to a virus includes the following:

Most cases of CFS occur sporadically. They occur in individuals and do not appear to be contagious.
There is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact.
No single virus has been implicated in chronic fatigue syndrome. Well-designed studies of patients who met strict criteria for chronic fatigue syndrome and of patients with chronic fatigue without any known cause have not found an increased incidence of any specific infections.

CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system. Some components appear to be over-reactive, while others appear to be under-reactive, but no consistent picture has emerged to explain CFS as a disease of the immune system.

Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities leading to CFS. (Most allergic people do not have CFS.)

Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases. Studies are inconsistent, however, in reporting the presence of autoantibodies (antibodies that attack the body's own tissues) in CFS, and the disease is unlikely to be due to autoimmunity.

Studies have observed that some patients who fit the strict criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as short a time as 10 minutes. Its immediate effects can be lightheadedness, nausea, and fainting.

However, not all CFS patients experience NMH, and studies have reported no higher incidence of NMH in chronic fatigue patients.

Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS to explain a causal role. Psychological factors, then, are unlikely to be a primary cause of CFS. They may play a role in increasing susceptibility to the disorder. Certainly, in many cases, CFS promotes psychological and social dysfunction.

Overall, doctors are increasingly adopting the view that CFS is probably a disease category that includes a range of subtypes, in the same way that cancer is a broad term within which numerous specific forms occur. Mounting evidence suggests that different subtypes of CFS have different causes and manifestations, and that these various types require different treatment approaches.

Research on subgroups of CFS is underway, but it is still in the very early stages. To date, however, clinical experience and limited data suggest that subgroups of CFS may include the following:

Post-ADD CFS: Young adults who had attention deficit disorder as children, who have flipped from hyperactivity to fatigue. Such patients have severe hypersomnolence (sleeping too much, sleeping any time or anywhere). Such patients respond well to psychostimulant medications.
Neurological CFS: These patients have more severe cognitive symptoms than do patients in the other groups. They may have trouble thinking, remembering, and paying attention. Although cognitive difficulties affect the vast majority of patients with CFS, this group experiences significantly more severe symptoms. Visual-spatial problems are common, as are sensitivities to light and noise. Other symptoms in this group include seizure-like episodes and other abnormalities that suggest temporal lobe seizures. Patients in this group tend to have severe sleep problems in which they never achieve stages 3 or 4 of the sleep cycle, awaken unrefreshed, and respond well to sleep-improving drugs.
Post-viral CFS versus gradual-onset CFS: According to some experts, an estimated 70% of patients are healthy until a particular illness strikes. In gradual-onset patients, however, symptoms develop gradually, and patients are unable to recall any specific viral or infectious illness that initiated the process.
Patients with immune abnormalities versus those without such abnormalities: Immune dysfunction (such as CD4, CD8, RNase, and TH1-TH2 imbalances) can leave some CFS patients unable to fight viruses effectively and cause their bodies to launch wrongful attacks against healthy tissues. Other CFS patients, however, do not have these immune abnormalities, or have only borderline shifts in immune factors.
CFS with Orthostatic Intolerance or Neurally Mediated Hypotension (NMH). These conditions cause dizziness (or unconsciousness) when a person stands up, due to a drop in blood pressure.
CFS with neuroendocrine abnormalities: Such problems may include dysregulation of cortisol or ACTH levels.
Activity level: There may be a difference between low-active versus high-active patients.
Patients with CFS alone: This subgroup may be different than CFS in patients with other conditions, such as fibromyalgia or multiple chemical sensitivity.

Observations that different treatments work for select patients appear to support the idea that subtypes of CFS require distinct approaches. The existence of subgroups may also explain why CFS researchers are frequently unable to replicate their results in subsequent studies; patient selection in studies to date has not reflected such careful discrimination. Researchers are now, however, working to define the subgroups of CFS and identify which treatments are most effective for each.

It should be noted that while the subgroup theory is interesting, in some cases the differences among patient populations may also reflect stages of disease. For instance, in the initial stages of the disease, many patients are symptomatic and have particular psychological symptoms, including alarm, denial, and anger. In contrast, patients in later phases of the disease typically have learned to cope better with their symptoms and have a degree of acceptance. Patients' mental and emotional status may have biological consequences that bear on their physical symptoms. Such a relationship is not yet documented in CFS patients, however, and remains subject to research.

Sudden- and Gradual-Onset CFS. One interesting theory is that CFS can be categorized as either sudden- or gradual onset, with each subgroup having different causes. In over half of patients, the onset is sudden, while the remaining patients have a slow onset. Some experts believe that sudden-onset CFS may be triggered by a virus or neurologic abnormality, while gradual-onset CFS might have a psychological or other cause. Supporting this theory was a study that looked at MRI scans of the brains of CFS patients who didn't have an accompanying psychiatric problem, and showed small injuries suggesting either a viral infection or neurologic problem. Still other experts believe that in some cases, gradual-onset CFS may be traced to cognitive disorders that were present during childhood, but went unrecognized until symptoms advanced into adulthood.

Diagnosis

It is very difficult to diagnose chronic fatigue syndrome. Even experts do not have a clear definition of what chronic fatigue actually is or what mechanisms in the brain or nervous system are responsible for it. The best diagnostic approach is to determine if the patient matches the criteria for CFS and to rule out other possible causes of symptoms.

In May 2006, the Centers for Disease Control and Prevention (CDC) released a revised definition for Chronic Fatigue Syndrome based on a consensus of many of the leading CFS researchers and doctors (including input from patient group representatives). In the revised definition, chronic fatigue syndrome is considered a subset of chronic fatigue, a broader category defined as unexplained fatigue that lasts for 6 months or longer. Chronic fatigue is considered a subset of prolonged fatigue, which is defined as fatigue that lasts for 1 month or more.

Unexplained chronic fatigue can be classified as CFS if the patient meets the following criteria:

Unexplained persistent or relapsing chronic fatigue that is either new or that started at a definite period of time; is not the result of ongoing exertion; is not substantially relieved by rest; and significantly reduces activities such as work, education, and social life.
Also, four or more of the following symptoms, which must have continued or recurred during 6 or more consecutive months of illness and must not have started before the fatigue:
- Significant impairment in short-term memory or concentration
- Sore throat
- Tender lymph nodes
- Muscle pain
- Joint pain without swelling or redness
- Headaches of a new type, pattern, or severity
- Unrefreshing sleep
- Malaise that lasts more than 24 hours after exertion

Any active medical condition that may explain the presence of chronic fatigue, such as:
- Untreated hypothyroidism
- Sleep apnea and narcolepsy
- Side effects of medication
An illness (such as cancer or hepatitis B or C virus infection) that relapsed or did not completely get better during treatment, that could explain the presence of chronic fatigue.
A past or current major depressive disorder, such as:
- Bipolar affective disorder
- Schizophrenia
- Delusional disorder
- Dementia
- Anorexia nervosa or bulimia nervosa
Alcohol or other substance abuse that occurs within 2 years of the onset of chronic fatigue and any time afterward.
Severe obesity as defined by a body mass index (BMI) equal to or greater than 45. (Note: Body mass index values vary considerably among different age groups and populations. No "normal" or "average" range of values can be suggested. The range of 45 BMI or higher was selected because it falls within the range of severe obesity.)

Any other abnormality found during an exam or other tests that could explain CFS symptoms must be resolved before further attempting to classify the condition.

In 2007, the National Institute for Health and Clinical Excellence (NICE) released new guidelines for the diagnosis and management of CFS in adults and children. According to these guidelines, CFS may be diagnosed if the person has disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition.

People with CFS also can have the following symptoms:

Difficulty thinking, concentrating, remembering, finding the right words, planning, and organizing
Difficulty sleeping
Dizziness or nausea
General malaise or flu-like symptoms
Headaches
Muscle or joint pain in many areas of the body without inflammation
Painful lymph nodes without disease
Fast heartbeat (palpitations) without heart problems
Sore throat
Worsening of symptoms with physical exertion

After ruling out other possible causes, the doctor should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children. Children should be diagnosed by a pediatrician.

A doctor should first take a careful personal and family medical history, which may include a psychological profile, as well as perform a thorough physical examination. Patients should be prepared to answer questions such as:

When did the fatigue first begin?
Does anything make it worse or better?
Is it better at certain times of the day?
Does physical activity make it worse?
Are there any other symptoms?
Has anyone else in the family ever complained of fatigue?
Is your personal and professional life stressful?

The doctor may also ask about any changes in weight or request a patient to monitor morning and afternoon body temperatures. Patients should report any drugs they are taking, including vitamins and over-the-counter or herbal medications.

Standard tests are typically recommended to rule out specific conditions that can cause persistent fatigue. These tests include:

Blood count
Blood tests for gluten sensitivity
C-reactive protein
Creatine kinase
Erythrocyte sedimentation rate or plasma viscosity
Liver function
Random blood sugar (glucose)
Serum calcium
Serum creatinine
Serum ferritin levels (only in children)
Thyroid function
Urea and electrolytes
Urine test for protein, blood, and glucose

No blood, urine, or other laboratory test can specifically diagnose CFS. If any test is abnormal, it is not useful for diagnosing CFS specifically, and the doctor should look for other causes of these abnormalities.

That being said, research published in 2005 found that certain components in urine were unique in people with CFS, and may someday be considered biomarkers of the disease. Additionally, antibodies to Epstein-Barr virus and increased levels of isoprostanes -- markers of oxidative stress -- have been found in the blood of people with CFS.

Among the many other common conditions that can lead to feelings of temporary exhaustion are the following:

Depression
Infections
Pregnancy
Extreme exercise
Excessive stress

In most of these cases, fatigue can be relieved with adequate rest. It is important to note that longstanding fatigue can be the harbinger of a serious medical or psychological problem. A number of more serious conditions may cause persistent fatigue and other symptoms of CFS and should be ruled out. Patients and doctors should not overlook these diseases, even if the conditions have been previously treated, because they may not have completely resolved or they may cause residual fatigue. Doctors can usually distinguish these diseases from CFS after a clinical evaluation and laboratory testing.

Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis is marked by fatigue and swollen glands. It primarily affects adolescents and young adults. Some patients may have lingering fatigue that lasts for many months and blood tests that indicate a persistence of the Epstein-Barr virus (EBV), which causes mononucleosis.

Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis, are caused by autoimmunity, a condition in which the person's immune system attacks the body's own tissues. The early symptoms of these conditions may mimic some of those that appear in CFS, such as muscle and joint pain and fatigue. These diseases, like CFS, also occur more often in women than in men. Most of these conditions can be confirmed with laboratory or x-ray/radiologic findings. However, some autoimmune diseases may evolve slowly, and even if a diagnosis of chronic fatigue syndrome is considered, doctors should keep track of any changes in symptoms over time in order to rule out these serious illnesses.

Post-Lyme Disease Syndrome. Rarely, patients treated for a diagnosis of Lyme disease continue to have nonspecific symptoms, which can last for years after antibiotic treatment and that resemble symptoms of chronic fatigue syndrome.

Psychosis and Severe Mental Disorders. The Centers for Disease Control (CDC), which set up the definitions in the U.S. for research in chronic fatigue syndrome, recognizes depression as one of the symptoms of CFS. However, according to the CDC, anyone with a history of major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia, does not meet the criteria for chronic fatigue syndrome.

Symptoms of major depression include the following:

A depressed mood every day
Significant weight gain or loss (10% or more of an individual's typical body weight)
Insomnia or excessive sleeping
Restlessness or a sense of being slowed down
Low energy every day
Worthless or inappropriately guilty feelings
An inability to concentrate or to make decisions
Suicidal thoughts

Major depression is likely to be responsible if a person has several of these symptoms and no physical symptoms (such as sore throat, aches and pains, or fever). The longer fatigue has continued without such physical symptoms, the more likely that the diagnosis is depression.

Of note, a persistent form of minor depression called dysthymia may be more difficult to differentiate from CFS and may actually account for a subset of CFS cases. Dysthymia is characterized by many of the same symptoms that occur in major depression, but they are less intense and last much longer, at least two years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities.

Patients with depression and those with CFS generally perceive their illnesses differently:

Patients with depression have significantly lower self-esteem, more thought distortions (for instance, focusing on the negative or personalizing their situations), and believe their conditions stemmed from psychological factors.
CFS patients, even those with concurrent depression or dysthymia, tend to identify medical causes as the source of their problems and to focus on physical symptoms.

Many previously healthy patients with CFS become depressed and anxious because they feel so exhausted all the time. CFS may also lead to highly stressful socioeconomic situations, such as social isolation and poverty, that can contribute to and even cause emotional disorders in susceptible individuals, which in turn can worsen CFS.

Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and can be confused with CFS:

Sleep apnea is a common disorder that can cause daytime fatigue without the patient being aware of the problem. Apnea is actually a breathing disorder often marked by loud snoring and thrashing in bed. A person may not realize the problem exists unless it is brought to his or her attention by a sleeping partner or observer.
Narcolepsy is a peculiar and rare disorder in which a person suddenly falls asleep without any previous signs of fatigue.
Other sleep disorders that cause daytime fatigue include insomnia and restless legs syndrome.

Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation. Non-restorative sleep and nighttime restlessness are the most common complaints of people with CFS.

Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause one or more of CFS symptoms, including arthritic symptoms, fever, and fatigue.

Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by the weight. People who are obese are also at particular risk for sleep apnea, which can confuse the diagnosis.

Other Medical Conditions that Usually Rule Out CFS. Many diseases, both benign and serious, can fully explain prolonged or chronic fatigue, including:

Hepatitis
Anemia
Hemochromatosis (a hereditary disease caused by iron overload) infections
Various forms of cancer
Neuromuscular diseases (such as myasthenia gravis)
Hypothyroidism
Diabetes

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependency on or abuse of alcohol or illicit drugs may manifest as chronic fatigue. Medications should be considered as a possible cause of fatigue if an individual has recently started, stopped, or changed medicines. Withdrawal from caffeine can produce depression, fatigue, and headache.

Prognosis

The physical severity of chronic fatigue syndrome varies. Most commonly, patients with CFS report that they have trouble fulfilling both home and work responsibilities.

CFS sufferers typically work part-time. In extreme cases, patients are severely disabled and even bedridden. Such patients can do virtually nothing, including even light housework.

Patients with CFS are more likely to lose their jobs, possessions, and support from friends and family than are people who have other conditions that cause fatigue.

Most patients say that while fatigue is the most incapacitating symptom, mental impairment, such as an inability to concentrate or remember, is the most distressing symptom. The effects of CFS on mental functioning are complex, however. Some experts believe that the impaired mental functioning is due to depression, which is common in CFS patients.

Some studies indicate that, although general intelligence is not impaired, CFS patients test lower in certain mental functions, particularly speed and efficiency in processing complex information, and that 40 - 60% have memory impairments. In such studies, this impaired mental function occurs regardless of the presence or absence of depression or other psychiatric disorders.

Because the illness remains elusive and poorly defined, and there are few objective measures for recovery, experts have found it difficult to determine the long-term course of the disease. Many patients are not covered by insurance or have difficulty finding good care, so available statistics may be incorrect. Bearing these factors in mind, some studies have reported that more than half of patients who complain of chronic fatigue are still fatigued at 2 years. Although a variety of studies have attempted to identify factors that predict a more chronic or severe course, no clear conclusions can be made. Even if patients get progressively worse, however, the disorder is not fatal.

Although children with symptoms of chronic fatigue have not been as rigorously studied as adults, limited evidence suggests that CFS can be significantly disabling in young people. Studies report that adolescents who meet the criteria for CFS also have greater anxiety, depression, and school absenteeism than their peers. Still, some studies indicate that children have a better prognosis than adults and that most will recover after 1 - 4 years. Several studies have indicated that cognitive-behavioral therapy is an effective treatment for adolescents with CFS.

Treatment

There is no proven or reliable cure for CFS, and no drug has been developed specifically for this disorder. Because CFS remains poorly understood, many patients have problems finding good care. Overall, the recommended strategy for treatment includes a combination of the following:

A healthy diet
Antidepressant drugs in some cases, usually low-dose tricyclics
Cognitive-behavioral therapy (CBT) and graded exercise for certain patients
Medication
Sleep management techniques

Patients with the best chance for improvement are those who remain as active as possible and who seek to have some control over the course of the disorder. Patients should choose physicians who are willing to consider the problem as a medical condition with psychiatric components. They should be very wary, however, if the physician recommends excessive and expensive treatments that may have serious adverse effects and that have no proven benefits. For patients with severe CFS that cannot be managed with lifestyle changes and standard medications, asking the physician about enrolling in any available clinical trials may be helpful.

Cognitive-Behavioral Therapy

CBT is designed to help CFS patients regain a sense of control, and is proving to have substantial benefits for some patients. Some experts believe that patients who are diagnosed with CFS should be referred to therapists trained in cognitive-behavioral therapy. (Psychoanalysis and other interpersonal psychological therapies, which are concerned with subconscious thoughts and early childhood memories, are not generally helpful for the CFS patient.)

The Goals of Cognitive-Behavioral Therapy. The primary goals of cognitive-behavioral therapy (referred to below as just cognitive therapy) are to change any distorted perceptions that individuals have of the world and of themselves, and to change their behavior accordingly. For CFS patients, this means learning to think differently about their fatigue and to improve their ability to deal with stressful situations and manage their disorder. It can also help manage their sleep problems and find the appropriate activity levels for them. Cognitive therapy is particularly helpful in defining and setting limits, behaviors that are extremely important for these patients.

The Procedure. CBT is usually performed over 6 - 20 sessions, each lasting about an hour. Patients are also given homework, which usually includes keeping a diary and attempting tasks that they have avoided because of negative attitudes.

A typical cognitive therapy program may involve the following measures:

Keep a Diary. The patient is almost always asked to keep an energy diary, which can be a key component of CFS cognitive therapy. The diary serves as a general guide for setting limits and planning activities. The patient uses the diary to track any factors, such as a job or a relationship that may be making the fatigue worse or better. It is also used to track the times of day when energy levels are at their highest and lowest peaks.
Adjust Schedule. The patient adjusts schedules to conform to energy peaks and valleys recorded in the diary. For instance, the patient may plan to take a nap during low-energy times and plan important activities during high-energy times. Developing fairly rigid daily routines around probable energy spurts or drops may help establish a more predictable pattern.
Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs (such as "I'm not good enough to control this disease, so I'm a total failure."), and to use coping statements ("Where is the evidence that I can control this disease?")
Be Flexible. Energy levels will most likely never be entirely predictable. Patients must be prepared to adapt to energy variations. Instead of taking a long nap, for instance, patients may need 5- to 10-minute rest periods every hour or more, possibly involving relaxation or meditation.
Set Limits. Limits are designed to keep both mental and physical stress within a manageable framework so that patients do not get discouraged by forcing themselves into situations in which they are likely to fail. For example, tasks are broken down into incremental steps and patients focus on one step at a time.
Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.
Manage Impaired Concentration. Patients seek out activities that are appealing, focus attention, and help increase alertness. They learn to request instructions given as concise, simple statements. External distractions, such as music or talking, are kept to a minimum.
Accept Relapses. Over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of treatment- or self-failure.

Using both self-observation and specific tasks, patients gradually shift their fixed ideas that they are helpless against the fatigue that dominates their lives. They move to the perception that fatigue is only one negative and, to a degree, a manageable experience among many positive ones.

Success Rates. One review of CFS trials reported that, of all therapies available to CFS patients, only cognitive behavioral therapy (CBT) and graded exercise showed conclusive benefits. Although CBT doesn't appear to bring patients completely back to normal, research has found that people who used the therapy had higher mental health scores, and were able to walk faster and with less fatigue than those who didn't use CBT. A 2005 study found that cognitive therapy is an effective treatment for adolescents with CFS. Patients who received CBT reported improvements in fatigue, functional status, and school attendance.

Not all studies support the benefits of cognitive therapy for CFS. It is important to note that different therapists may have different fundamental assumptions about CBT and may use different techniques. For instance, some therapists believe that CFS is purely a psychological problem and that patients must reject the notion of physical causes, abandon all reliance on assistive devices, and participate in challenging exercise programs. In contrast, other therapists do not attempt to change patients' underlying beliefs at all, but instead focus on helping patients conserve energy and better cope with the limitations of their illness. When considering CBT, patients and their families must be aware of such important differences.

Regardless of whether specific organic causes of CFS are identified, the power of the mind to improve or oppose health problems is significant, and treatments that promote a positive outlook are beneficial for any disease.

A number of studies have suggested that a graded exercise program, in which patients perform increasingly more intense levels of exercise tailored to their individual abilities, has benefits for many patients with CFS. Exercise is best performed in combination with cognitive behavioral therapy.

Reports have found that 75% of CFS patients who were able to engage in exercise, particularly aerobic exercise, reported less fatigue and better daily functioning and fitness after a year. A 2004 review of clinical trials found that exercise therapy is beneficial for CFS, particularly when combined with patient education.

Some patient groups and experts contend that such studies use only patients with less severe conditions and do not apply to many CFS patients. Many patients have severe conditions, and some are very incapacitated (such as being wheelchair bound). These patients are unlikely to undergo even graded exercise. All CFS patients, in fact, have a lower exercise capacity than healthy individuals, and over-exercising can intensify symptoms. Some patients experience profound fatigue following even modest exercise. It is the primary factor in perpetuating the low-activity levels observed in these patients.

The following tips may be helpful for CFS patients when embarking on an exercise program:

Work with your health care provider to determine a good starting level of activity for you. Start slowly and incrementally, beginning with as few as 3 - 5 minutes of moderate exercise a day. The goal is to increase activity by about 20% every 2 - 3 weeks, until you can handle about 30 minutes a day. Once you reach 30 minutes a day, start to increase the aerobic intensity of your workouts. (Capacity varies greatly among CFS sufferers, however, and some may not be able to achieve this.)
Establish limits and keep within them in order to avoid overexertion and relapse.
Experiment with different forms of physical activity that suit your available energy levels. Some patients report great benefits from yoga or Tai Chi, which combine exercise with meditation.
Setbacks will occur, but do not become discouraged.

Work with your health care provider to find a level of activity you can handle. Then gradually increase your activity level. Activity management should involve:

Balancing your time between activity, rest, and sleep
Spreading out more challenging tasks throughout the week
Breaking big tasks into smaller, more manageable ones
Avoiding doing too much on days when you feel tired

Although there is no evidence to support any specific dietary factors in CFS, patients should be sure to maintain a healthy diet that includes:

Plenty of fresh dark-colored fruits and vegetables, which are rich in antioxidants
Fiber-rich foods
Limited saturated fats (found in animal products)
Omega-3 essential fatty acids, found in certain fish and oils
Increased salt (only for those with demonstrated low blood pressure)
Starchy foods, particularly for nausea

Stress Reduction Techniques. One panel of experts concluded that relaxation and stress-reduction techniques were helpful in managing chronic pain. These techniques also can help relieve the stress associated with the disease. They are not useful, however, as the primary treatment for CFS. A number of relaxation techniques are available:

Biofeedback
Deep breathing exercises
Hypnosis
Massage therapy
Meditation
Muscle relaxation techniques
Yoga

Light Therapy. Patients with seasonal affective disorder (SAD) experience more depression during the winter, when the hours of sunlight decrease. With light therapy (phototherapy), the patient sits for about 30 minutes each day a few feet away from a box-like device that emits very bright fluorescent light (4,000 lux). Light therapy is best performed immediately after awakening in the morning.

Some CFS patients don't have much improvement from light therapy. However, the treatment may still help some patients with CFS whose symptoms are similar to those of patients with seasonal affective disorder (SAD).

Supportive Family and Groups. Having strong, supportive relationships with family and friends can help CFS patients get better. However, CFS patients should try not to impose unreasonable expectations on loved ones that cannot be met. Ongoing support groups with fellow patients may be very helpful. In one study, sharing experiences in a group therapy setting proved to be the most valuable component in treatment, and one that improved patients' coping abilities.

Medications

No medications are specifically approved for the treatment of CFS. However, some may be useful for pain or other specific symptoms, or in cases where CFS may have a specific cause. Doctors generally use combinations of drugs to accomplish specific goals, such as medication at night to improve sleep and medication in the morning to improve cognition and energy. Treatment is very individualized.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Patients with CFS may find relief using NSAIDs -- common pain relievers that reduce pain and swelling. Types of NSAIDs include aspirin, ibuprofen (Motrin, Advil, Nuprin), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox).

Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Due to its proven cardiovascular benefits, aspirin was excluded from these labeling revisions.

NSAIDs can also increase blood pressure, particularly among people already being treated for hypertension. (About 12 - 15% of elderly people take both an NSAID and an antihypertensive drug.) Piroxicam, naproxen, and indomethacin appear to pose the greatest risk of high blood pressure. Sulindac has the smallest effect.

Other side effects of NSAIDs include:

Dizziness
Ringing in the ears
Headaches
Skin rashes
Possibly depression

NSAIDs can cause kidney damage. (The damage gets better once the patient stops using the drug.) People with high blood pressure, severe circulation disorders, or kidney or liver problems, as well as people taking diuretics or oral hypoglycemics, must be closely monitored if they need to use NSAIDs on a long-term basis. Because NSAIDs reduce blood clotting, NSAID users scheduled for surgery should stop taking those drugs a week before the operation.

COX-2 Inhibitors (Coxibs). Coxibs block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of cardiovascular events, skin rashes, and other adverse effects prompted the FDA to re-evaluate the risks and benefits of the COX-2 drugs. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. Celecoxib (Celebrex) was still available at the time of this report, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Because of the association between depression and CFS, antidepressants are often tried, with varying degrees of success. Common side effects of many antidepressants include:

Dry mouth
Restlessness
Reduced sexual drive
Slightly increased heart rate
Constipation

Virtually all antidepressants have complicated interactions with other drugs, and some are very serious.

Tricyclic Antidepressants. Antidepressants known as tricyclics may be particularly helpful for CFS patients. For example, the tricyclic amitriptyline (Elavil) is known to relieve many of the symptoms of CFS, including sleeplessness and low energy levels. These drugs may provide benefits by promoting deep sleep and inhibiting pain pathways in the nervous system. Improvement in symptoms can take 3 - 4 weeks. Other tricyclics include doxepin (Sinequan), desipramine (Norpramin), nortriptyline (Pamelor), clomipramine (Anafranil), and imipramine (Tofranil, Janimine). Patients with CFS normally respond to much lower doses than those used to treat people with depression. In fact, many CFS patients cannot tolerate the higher doses commonly used to treat the psychiatric disorder. Like all medications, tricyclics must be taken as directed. Overdose can be life-threatening. Tricyclics should not be taken together with SSRIs, because of the possibility of dangerous side effects.

Other Antidepressants. Newer, so-called designer SSRIs, including bupropion (Wellbutrin), nefazodone (Serzone), or mirtazapine (Remeron), affect combinations of different neurotransmitters, and some may have moderate benefits for CFS patients. For example, in one study, nefazodone improved mood, fatigue, and sleep disturbances.

SSRIs. The popular antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) may be helpful for the subgroup of CFS patients who experience significant depression. They include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Cymbalta (duloxetine) is a new antidepressant that is classified as a selective serotonin and norepinephrine reuptake inhibitor (SSNRI).

In a 2006 UK study of 275 CFS patients, those treated with antidepressants recovered faster than those who did not receive the medication. SSRIs were found to be more effective than tricyclic antidepressants, producing improvements, including a reduction in fatigue, that were maintained at the 3-year follow-up.

Psychostimulants. Psychostimulants may be helpful for a subgroup of patients with CFS who have cognitive problems, such as difficulty concentrating, memory problems, and other attention deficit disorder (ADD)-like characteristics. Psychostimulants include Dexamphetamine, Adderal, methylphenidate (Ritalin) and Ritalin-like drugs such as Focalin, Concerta, Ritalin LA, and Metadate, as well as Strattera and Provigil. The NICE guidelines for CFS do not advise taking Dexamphetamine or Ritalin. However, a 2007 study found that taking two 10 mg doses of Ritalin each day works much better than placebo at relieving fatigue and concentration problems. More research is needed to study the long-term effects of Ritalin on CFS patients.

Because of the difficulties in treating chronic fatigue syndrome, many patients seek alternative therapies. Some, such as acupuncture, yoga, and relaxation techniques, may be helpful and are not dangerous. No scientific evidence exists that vitamin and mineral supplements will relieve CFS, but some people do report that they find supplements helpful.

Herbal and Supplements. Popular herbal and dietary supplement remedies for CFS include coenzyme Q10, vitamin B12, vitamin C, magnesium, multivitamins, DHEA, ginseng, and acetylcarnitine. None have been rigorously tested. Some herbs, such as St. John’s wort, ginkgo, and comfrey, may cause serious side effects and drug interactions.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that can affect the body's chemistry can, like any drug, 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.

Some so-called natural remedies have been found to contain standard prescription medication. Of specific concern are studies suggesting that up to 30% of herbal patent remedies imported from China have been laced with potent pharmaceuticals, such as phenacetin and steroids. Most reported problems occur in herbal remedies imported from Asia. One study reported that a significant percentage of such remedies contain toxic metals.

CFS patients should be wary of any company that promises a cure or urges the purchase of expensive but useless and sometimes potentially dangerous treatments, such as the following:

St. John's wort. This herbal remedy is being investigated for mild depression. In one study, St. John's wort lessened fatigue in CFS patients, even in those who did not consider themselves to be depressed. However, the substance may have some serious side effects; for example, it can interact with blood thinning medication. In a brand comparison, only three St. John's wort products out of eight contained within 10% of the active ingredient amounts claimed on the labels.
Melatonin. Some patients use melatonin, based on the association between CFS and possible sleep abnormalities. However, the small amount of research available has not shown melatonin to be helpful.
Gingko. Although the risks for gingko appear to be low, there is an increased risk of bleeding at high doses. In addition, gingko can interact with high doses of vitamin E and anti-clotting medications. Commercial gingko preparations have also been reported to contain colchicine, an agent that can be harmful in pregnant women and people with kidney or liver problems. Some brands of gingko have no effect at all.
Comfrey. Comfrey is an herbal remedy used for a number of inflammatory problems. Recently, evidence has emerged that comfrey can be toxic to the liver, and animal studies have reported a possible cancer risk. Comfrey is banned in Canada and other countries, but is widely available in the U.S.

Of particular note for CFS patients are products containing the ingredient Ma Huang, which contains the stimulants ephedrine and kola nut, a caffeine source. Serious adverse reactions, including seizures, psychosis, and several deaths, have been reported in people taking this supplement for increased energy or weight loss. Products that have only one of these ingredients do not appear to have the same effect, but people should take so-called energy boosting supplements only with the knowledge and recommendation of their doctor.

Other alternative remedies with no proven benefit and possible toxic and dangerous side effects include the following:

Hydrogen peroxide injection (can cause blood clots or strokes)
Megadoses of vitamins (can be toxic and have shown no benefits)
High colonic enemas
Bee pollen (can cause an allergic reaction)
Injections of liver extract
Superoxide dismutase (SOD)

Resources

www3.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/cfs - Centers for Disease Control and Prevention, Chronic Fatigue Syndrome information
www.cfids.org -- The Chronic Fatigue and Immune Dysfunction Syndrome Association of America
www.ncfsfa.org -- National Chronic Fatigue Syndrome and Fibromyalgia Association
www.aacfs.org -- American Association for Chronic Fatigue Syndrome
www.theacpa.org -- American Chronic Pain Association
www.ampainsoc.org -- American Pain Society
www.iasp-pain.org -- International Association for the Study of Pain
www.medicalacupuncture.org -- American Association of Medical Acupuncture
www.aabt.org -- Association for Advancement of Behavior Therapy

References

Armitage R, Landis C, Hoffmann R, Lentz M, Watson NF, Goldberg J, Buchwald D. The impact of a 4-hour sleep delay on slow wave activity in twins discordant for chronic fatigue syndrome. Sleep. 2007;30:657-662.

Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006;119:e23-30.

Chia J, Chia AY. Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. J Clin Pathol. 2008;61:43-48.

Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier, 2007.

Hampton T. Researchers find genetic clues to chronic fatigue syndrome. JAMA. 2006;295(21):2466-2467.

Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes preciptated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575. Epub Sept 1.

Jones JF. Orthostatic instability in a population-based study of chronic fatigue syndrome. Am J Med. 2005;118:1415.

Kato K, Sullvan PF, Evengard B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006;63(11):1267-1272.

Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2006. Nov 18 (Epub ahead of print).

National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management of CFS/ME in adults and children. August 2007.

O'Dowd H, Gladwell P, Rogers CA, Hollinghurst S, Gregory A. Cognitive behavioural therapy in chronic fatigue syndrome: a randomized controlled trial of an outpatient group programme. Health Technol Assess. 2006;10:iii-iv, ix-x, 1-121.

Thomas MA, Smith AP. An investigation of the long-term benefits of antidepressant medication in the recovery of patients with chronic fatigue syndrome. Hum Psychopharmacol. 2006;21(:503-509.

Vermeulen RC, Scholte HR. Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data. J Transl Med. 2006;4:34.

Review Date:
1/4/2008
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., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

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

adam.com

Depression

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

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

Antidepressants and Suicide Risk

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

Antidepressants During Pregnancy

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

Introduction

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

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

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

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

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

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

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

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

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

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

5. Feelings of agitation or a sense of intense slowness

6. Loss of energy and a daily sense of tiredness

7. Sense of guilt or worthlessness nearly all the time

8. Inability to concentrate occurring nearly every day

9. Recurrent thoughts of death or suicide

In addition, other criteria must be met:

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

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

Click the icon to see an image of childhood depression.

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

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

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

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

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

Causes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following are danger signs in young people:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Risk Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Complications of Depression

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

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

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

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

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

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

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

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

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

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

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

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

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

Diagnosis

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

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

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

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

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

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

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

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

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

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

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

Treatment

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

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

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

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

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

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

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

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

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

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

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

Health professionals who can prescribe antidepressants include:

Doctors, including psychiatrists
Some nurse clinicians

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

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

Tips for Selecting a Therapist:

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

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

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

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

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

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

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

The use of antidepressants in the elderly is problematic:

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

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

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

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

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

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

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

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

Antidepressants and Drug Treatment Guidelines

Major classes of antidepressants include:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Side Effects of SSRIs. Side effects may include:

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

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

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

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

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

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

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

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

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

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

Tricyclics are sometimes grouped into two categories:

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

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

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

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

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

Tricyclics can have serious, although rare, side effects:

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

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

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

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

Atypical depression
Eating disorders
Post-traumatic stress disorder
Borderline personality

Side Effects. MAOIs commonly cause the following side effects:

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

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

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

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

Psychotherapy

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

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

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

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

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

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

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

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

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

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

Other Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Lifestyle Changes

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.

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

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

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

The following guidelines are recommended:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Resources

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

References

Allen JJ, Schnyer RN, Chambers AS, Hitt SK, Moreno FA, Manber R. Acupuncture for depression: a randomized controlled trial. J Clin Psychiatry. 2006 Nov;67(11):1665-73.

Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM; National Birth Defects Prevention Study. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2684-92.

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.

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Eranti S, Mogg A, Pluck G, et al. A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. Am J Psychiatry. 2007 Jan;164(1):73-81.

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George MS, Nahas Z, Borckardt JJ, et al. Brain stimulation for the treatment of psychiatric disorders. Curr Opin Psychiatry. 2007 May;20(3):250-4; discussion 247-9.

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Hetrick S, Merry S, McKenzie J, Sindahl P, Proctor M. Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004851.

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Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial. BMC Med. 2006 Jun 23;4:14.

Kellner CH, Knapp RG, Petrides G, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry. 2006 Dec;63(12):1337-44.

Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry. 2007;68 Suppl 8:35-41.

Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61.

Louik C, Lin AE, Werler MM, Hernández-Díaz S, Mitchell AA. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2675-83.

Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):593-602.

Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007 Jun;68(6):826-31.

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

A.D.A.M. Copyright

adam.com

Smoking

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

In This Report

Highlights
Introduction
Nicotine Addiction
Health Risks
Secondhand Smoke
Smoking Bans
Quitting Smoking
Symptoms of Withdrawal
Failure to Quit
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Smoking and Your Health

Smoking may worsen knee osteoarthritis in men. A study published in the Annals of Rheumatic Disease found that male smokers have more pain and cartilage loss than men who do not smoke. Previous studies have not found such a link.
Smoking greatly increases the risk of age-related macular degeneration. An Australian study reports that smokers are four times more likely to develop the eye condition than those who have never smoked. Smokers also developed the condition at an earlier age.
Analysis of several studies suggests that smoking cigarettes and, in some cases, cigars or pipes, may reduce the risk of Parkinson's disease. However, smoking causes many other serious health conditions and should not be considered a means for preventing Parkinson's.
A small study suggests that infants who are breastfed just after their mother smokes sleep less than those whose mothers did not smoke.

Smoking Cessation

Certain genes may make it easier for you to quit smoking. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Smoke Free Zones

More and more households in the United States are banning smoking. The U.S. Centers for Disease Control and Prevention (CDC) reports that 75% of households now forbid smoking at any time or place in the home.

Smoking in the Movies

Teens who see actors smoke on screen are more likely to become established smokers, according to an updated study in the Archives of Pediatric Adolescent Medicine. Study authors say the likelihood of smoking increases with exposure to movies that depict such behavior.

Introduction

More than 20% of adults in the United States smoke, according to a 2006 report by the U.S. Centers for Disease Control and Prevention (CDC). More than 80% of them smoke every day. Although smoking had steadily declined among adults in recent years, the trend now appears to have stalled. Between 2004 and 2005, the CDC says there was no observable change in smoking rates among U.S. adults.

The addictive effects of tobacco have been well documented. Tobacco is considered to be a mood and behavior altering substance that is psychoactive and abusable. Tobacco is believed to be as potentially addictive as alcohol, cocaine, and morphine. Tobacco and its various components increase the risk of cancer (especially in the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, and cervix), heart attacks, strokes, and chronic lung disease.

The younger children start smoking, the more likely they will smoke as an adult. Smoking is often immediately addictive. According to the American Cancer Society, the earlier you start smoking, the more likely you are to develop long-term nicotine addiction.

In the past, advertising was responsible for encouraging some teens to smoke. New regulations have made it much more difficult for advertisers to promote smoking to young people. However, scenes that show people smoking are still common in movies and television shows, often in a positive light. This may be a major influence on the attitude toward smoking in children and adolescents. An updated study in the Archives of Pediatric Adolescent Medicine found that adolescents that watch movies that portray smoking are more likely to become established smokers.

To prevent children from smoking, parents should not smoke, and they should tell their child that they disapprove of smoking. Schoolchildren who believed that both their parents strongly disapproved of smoking were less than half as likely to smoke as those kids whose parents did not show as much disapproval towards smoking. Other research has supported these findings.

Children whose parents closely monitor their television and music-listening habits are less likely to drink, use drugs, and smoke cigarettes.

Neglected children, or children with absentee parents, were four times as likely to abuse drugs, drink, and smoke as children living with parents who were regularly present and who offered a structured lifestyle.

In a 2002 study, children who regularly attended religious services were also less likely to smoke.

Doctors can have a major effect on young people. However, in one survey, less than half of teenagers had ever been asked by their doctors if they smoked or were counseled not to smoke, even though most teen smokers said they would admit to it if asked.

More American men smoke than women. The following chart details the rate of current smoking in the United States among adults aged 18 years and over, grouped by age and sex:

Age	Total	Men	Women
18 - 44 years	24.1%	27.1%	21.2%
45 - 64 years	21.9%	25.2%	18.8%
65 years and older	8.6%	8.9%	8.3%

Source: CDC/National Health Interview Survey 2005

While the number of adults over 65 who smoke is lower than those in other age groups, older adults usually have smoked for a long time (about 40 years) and tend to be heavier smokers, according to the American Lung Association. Because of this, older smokers are more likely to have smoking-related illnesses.

Caucasian students (under age 18) are more likely to smoke than Hispanics and African-Americans. In 2005, the rate of smoking was highest among American Indians and Alaskan natives. Hispanics and Asians had the lowest rates.

In general, the rate of smoking is highest in the Midwest and South and lowest in the Northeast and West. Utah has the lowest rate of smoking in the United States.

A major U.S. government study reported that people who have not graduated from high school or received their General Education Development (GED) certificate tend to have higher smoking rates than those who attended college.

Higher rates of cigarette smoking have been reported among adults who have earned a GED and those with a 9 – 11 grade education. The lowest rates are seen among those with advanced college degrees.

People with low self-esteem and adolescents with behavioral problems have a higher risk for smoking. Men and women with mental disorders are 50% more likely to smoke than those without such illness.

For example, depression and schizophrenia are known risk factors for smoking. Both may actually have biologic effects that are responsible for this higher risk.

Smoking is much more common among persons with disabilities than those without emotional, mental, or physical limitations. A 2007 Centers for Disease Control study found that the rate of smoking is nearly 50% higher among persons with disabilities. The CDC survey included those with mental illness and drug and alcohol addictions in the disabled group.

Evidence now strongly supports the idea that genes play a role in a person's dependence on nicotine. Researchers are now targeting specific genes that may be responsible for nicotine dependence. So far, research has been shown that there is a common genetic vulnerability to both nicotine and alcohol dependence.

Some studies suggest that the cheaper it is to buy cigarettes and smoke, the more widespread smoking will be. For example, states that have low taxes on cigarettes have a high proportion of smokers. Making it more expensive to smoke may reduce the number of smokers.

Nicotine Addiction

Nicotine is the chemical in cigarettes that makes them addictive. Higher levels of nicotine in a cigarette can make it harder to quit smoking. A report by the Massachusetts Department of Health found that the amount of nicotine in cigarettes has steadily increased over the last 6 years. Higher nicotine levels were found in all cigarette categories, including “light" brands. Massachusetts is one of several states that require tobacco manufacturers to submit yearly reports regarding cigarettes.

Some researchers feel nicotine is as addictive as heroin. In fact, nicotine has actions similar to heroin and cocaine, and the chemical affects the same area of the brain.

Depending on the amount taken in, nicotine can act as either a stimulant or a sedative. Cigarette smoking has definite immediate positive effects. For example, it can:

Boost mood and relieve minor depression
Suppress little fits of anger
Enhance concentration and short-term memory
Produce a modest sense of well-being

Most smokers have a special fondness for the first cigarette of the day because of the way brain cells respond to the day's first nicotine rush. Nicotine, particularly taken in the first few cigarettes of the day, increases the activity of dopamine, a chemical in the brain that elicits pleasurable sensations, a feeling similar to achieving a reward.

Over the course of a day, however, the nerve cells become desensitized to nicotine. Smoking becomes less pleasurable, and smokers may be likely to increase their intake to get their "reward." A smoker develops tolerance to these effects very quickly and requires increasingly higher levels of nicotine.

A smoker may "forget" their craving for nicotine if a part of the brain called the insula becomes damaged. A 2007 study published in the journal Science found that smokers with brain damage to this area were 136 times more likely to forget their addiction to nicotine. The findings may one day lead to new drugs that better help a person quit.

Smokeless tobacco, also called spit tobacco, includes chewing tobacco (dip and chew), tobacco powder (snuff), as well as flavored tobacco lozenges. These products also contain nicotine. There are two forms of spit tobacco.

These products allow tobacco to be absorbed by the digestive system or through mucous membranes. Smokeless tobacco contains at least 28 cancer-causing substances. Smokeless tobacco is not a safe substitute for smoking cigarettes or cigars. According to the National Institutes of Health, chewing on an average-size piece of chewing tobacco for 30 minutes can deliver as much nicotine as smoking three cigarettes.

Although research is inconsistent, some evidence suggests that smokeless tobacco produces a 50-fold increase in the risk of oral cancer, gingivitis, and tooth loss.

Health Risks

Smoking -- even just a few cigarettes a day -- has been linked to many serious health risks. Some are listed below.

According to the American Lung Association, smoking is directly responsible for about 90% of the deaths due to lung cancer. Smoking is also responsible for the majority of deaths due to chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis.

A study in the July 2006 American Journal of Respiratory and Critical Care Medicine showed that smokers with asthma who give up smoking can improve their lung function in as little as 1 week. The small study involved 21 smokers with asthma. Ten of them quit smoking for 10 weeks, while the others continued to smoke. After just a week, lung function test scores in those who stopped smoking improved considerably. In less than 2 months, lung function scores among those who stopped smoking improved by more than 15%.

Study authors say their findings show that there is a “reversible component to the harmful effects of smoking on the airways in asthma.”

All forms of tobacco raise heart attack risk. Smoking, chewing tobacco, and being exposed to secondhand smoke greatly increase the risk of a heart attack. In some cases, the risk of heart problems in people who smoke or are exposed to smoke may be three times greater, according to a study published in the journal Lancet. However, the study also found that the risk of a heart attack among those who stopped smoking slowly decreased over time.

Smoking has a negative affect on a man's sexuality and fertility. Heavy smoking is frequently cited as a contributory factor in impotence because it decreases the amount of blood flowing into the penis. One study noted that among men with high blood pressure, smoking caused a 26-fold increase in impotence.

Smoking impairs sperm motility, reduces sperm lifespan, and may cause genetic changes that can affect a man's offspring. One 2002 trial found that men or women who smoke have lower success rates with fertility treatments. An earlier study reported that men who smoke also have lower sex drives and less frequent sex.

Studies have linked cigarette smoking to many reproductive problems. Continuing to smoke during pregnancy may also cause health problems in the baby.

Negative effects of smoking on female fertility include:

Greater risk for infertility. Women at greatest risk for fertility problems are those who smoke one or more packs a day and who started smoking before age 18.
Earlier menopause. Women who smoke tend to start menopause at an earlier age than nonsmokers, perhaps because toxins in cigarette smoke damage eggs.
Pregnancy complications. Women who smoke have a greater risk for ectopic pregnancy and miscarriage.

Click the icon to see an image of an ectopic pregnancy.

Effects on Unborn Child. Smoking during pregnancy increases the risk for stillbirth, prematurity, and low birth weight in their babies. Women who smoke during pregnancy have lower levels of folate, a B vitamin that is important for preventing birth defects.

Children of mothers who smoke during pregnancy may also be at increased risk for obesity and diabetes.

Some women have particular genes that may make them especially likely to deliver low birth weight infants if they smoke, although newborns of all female smokers have a greater risk for low weight. The good news is that women who quit before becoming pregnant or even during the first trimester reduce the risk for a low birth weight baby to that of women who never smoked.

Women who want to become pregnant should make every attempt to quit and should use smoking cessation aids before they try to conceive. After birth, if new mothers cannot quit, they should at least be sure not to smoke in the same room as their infant.

Smoking and Breastfeeding. Smoking right before breastfeeding may interrupt the child's sleep patterns. A small study found that such infants sleep less than other infants, and that their sleep time dropped significantly as levels of nicotine in breast milk increased.

Smoking has many harmful effects on bones and joints:

Smoking can keep new bone from forming. Women who smoke are at high risk for loss of bone density and osteoporosis.

Click the icon to see an image of osteoporosis.

Postmenopausal women who smoke have a significantly greater risk for hip fracture than those who do not.
Men who smoke may have more severe symptoms of knee arthritis, according to a study published in the Annals of Rheumatic Disease.
Smokers are more apt to develop degenerative disorders and injuries in the spine.
Smokers have more trouble recovering from surgeries, including knee or hip replacements. A 2006 study published in the Journal of Bone & Joint Surgery suggests that smoking delays tendon-bone healing, which may lead to a slower recovery after rotator cuff repair surgery.
Smokers whose jobs involve lifting heavy objects are more likely to develop low back pain than nonsmokers.
Smoking may increase the risk of rheumatoid arthritis in some older women. A 2006 study in Annals of the Rheumatic Diseases showed that smoking nearly doubled the risk of rheumatoid arthritis in postmenopausal women who did not have the most established genetic risk factor for the disease, a genotype called HLA-DRB1 SE.

Click the icon to see an image of rheumatoid arthritis.

Smoking may increase the risk of developing diabetes. Researchers involved in the Insulin Resistance Atherosclerosis Study (IRAS) looked at the relationship between smoking and diabetes and found that 25% of smokers who started the trial with normal blood sugar had diabetes 5 years later compared to 14% of nonsmokers. The results were published in Diabetes Care.

A study released in 2006 supports earlier beliefs that smokers have a higher risk of developing glucose intolerance, a condition that precedes diabetes. The study, published in the British Medical Journal, involved 4,572 people. The findings suggest that chemicals in smoke could affect the pancreas. The pancreas is the organ that produces insulin, which helps control blood sugar (glucose) levels.

Smoking increases acid production in the stomach. It also reduces blood flow and production of compounds that protect the stomach lining.

Diverticulitis. One study suggested that smoking was a major risk factor in diverticulitis, a condition in which small bumps develop in the wall of the colon. In addition, smokers were at risk for complications from diverticulitis, including bleeding and abscess. Diverticulitis mostly affects people over age 50.

Inflammatory Bowel Disease. Smoking has mixed effects on inflammatory bowel disease. Inflammatory bowel disease is the collective term for ulcerative colitis and Crohn's disease. Smokers have been shown to have lower than average rates of ulcerative colitis, but higher than average rates of Crohn's disease. Smokers with Crohn's disease who quit are said to have less severe symptoms.

Click the icon to see an image of inflammatory bowel disease.

Peptic Ulcers. Results of studies on the effect of smoking on ulcers are mixed. Some evidence suggests that smoking delays the healing of gastric and duodenal ulcers. One study reported that after ulcers healed, about half of smokers relapsed after a year, and that all heavy smokers relapsed after 3 months. Other studies, however, have found no increased risk for ulcers in smokers. Smoking does not appear to increase susceptibility to Helicobacter pylori (H. pylori), the bacteria that causes many peptic ulcers.

Click the icon to see an image of peptic ulcers.

Hepatitis and Cirrhosis. Smoking is linked to increased liver scarring (cirrhosis) caused by either excessive drinking or chronic hepatitis B or C viruses.

Cyanide, a chemical found in tobacco smoke, interferes with thyroid hormone production. Smoking triples the risk for developing thyroid disease, particularly hyperthyroidism and hypothyroidism. Women smokers with subclinical hypothyroidism (a symptom-free condition in which the thyroid gland is mildly underactive) have a higher risk for developing full-blown hypothyroidism than their nonsmoking peers. Smoking has also been linked to goiter, a swelling of the thyroid that occurs in people who do not get enough iodine.

Click the icon to see an image of the thyroid.

Smokers are at increased risk for heart and circulatory problems and delayed wound healing after surgery. In one study, patients who were able to cut down or quit smoking 6 - 8 weeks prior to knee or hip replacement surgery were much less likely to suffer complications.

The following age-related conditions occur at higher rates in smokers than nonsmokers:

Cataracts. Quitting smoking reduces your chances of needing cataract surgery in the future, although not to the level seen with nonsmokers.

Click the icon to see an image of a cataract.

Age-related macular degeneration (AMD). AMD is a leading cause of blindness in older people. An Australian study, published in 2007 found that the condition is four times more likely in persons who smoke than those who have never done so. Symptoms of macular degeneration include a loss of central vision, which makes it difficult to read.
Gum disease and tooth loss. A government study found that more than half of the cases of severe gum disease in adults in the United States may be due to cigarette smoking.
Wrinkles. Studies confirm that smokers are nearly five times more likely to develop more and deeper wrinkles as they age compared to nonsmokers.
Baldness and premature gray hair. Certain chemicals in smoke break down in hair cells, which leads to hair damage.
Hearing loss, particularly high-frequency hearing loss. Some experts believe that losing the ability to hear high pitched sound in smokers may be due to a decrease in blood flow to the cochlea, the part of the ear that carries sound to the brain.
Incontinence. One study of 600 women indicated that smokers and former smokers are twice as likely to develop incontinence as women who never smoked.

Secondhand Smoke

Secondhand smoke is produced by a burning cigarette or other tobacco product. An estimated 4 million children a year get sick from being around secondhand smoke. Parental smoking has been shown to affect the lungs of infants as early as the first 2 - 10 weeks of life, and such abnormal lung function could persist throughout life.

Exposure to secondhand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children who have existing asthma.

Parental smoking is believed to increase the risk for lower respiratory tract infections (such as bronchitis or pneumonia) by 50%. Environmental exposure to smoke is thought to be responsible for 150,000 - 300,000 such cases every year.

Smoking Bans

Smoking bans have spread across the country. By October 2007, at least 22 states and the District of Columbia have passed some type of law banning smoking in almost all public places and workplaces, including restaurants and bars. The date an individual state's ban takes effect varies greatly; some do not take effect until 2008 or 2009.

As of January 1, 2006, nine states were considered "smoke-free" -- California, Connecticut, Delaware, Massachusetts, Maine, New York, Rhode Island, Vermont, and Washington.

Quitting Smoking

It's never too late to quit smoking. According to the American Cancer Society, about half of all smokers who keep smoking will die from a smoking-related disease. Quitting has immediate health benefits.


Time after last cigarette	Physical Response
20 minutes	Blood pressure and pulse rates return to normal.
8 hours	Levels of carbon monoxide and oxygen in the blood return to normal.
24 hours	Chance of heart attack begins to decreases.
48 hours	Nerve endings start to regrow. Your ability to taste and smell increases.
72 hours	Bronchial tubes relax and the lungs can fill with more air.
2 weeks to 3 months	Improved circulation; lung function increases up to 30%.
1 to 9 months	Decreased rates of coughing, sinus infection, fatigue, and shortness of breath; regrowth of cilia in the airways, increasing the ability to clear mucus and clean the lungs and reducing the chance of infection; overall energy level increases.
Long-Term Effects	After a year, the risk of dying from heart attack and stroke is reduced by up to 50%.

According to the National Institutes of Health, about 40% of smokers who want to quit make a serious attempt to do so each year, but fewer than 5% actually succeed. A June 2006 report published by the NIH says that the available smoking cessation products and therapies are greatly underused. If more smokers asked for or were offered such help, the agency says quit rates could double or triple.

Some people have certain genes that make quitting easier. Researchers at Duke University have identified more than 200 genes that distinguish those who have successfully kicked the habit. It is the first time such genes have been identified. The findings could lead to new smoking cessation therapies that target a person's specific genetic makeup.

Methods of quitting smoking include counseling and support groups, nicotine patches, gums, lozenges, and sprays, smoking cessation pills, and slowly cutting back on the number of cigarettes smoked (incremental reduction).

About 4% of smokers who quit without any outside help succeed. Nevertheless, most people try to quit alone, and many have reported activities that can help the process of withdrawal. The primary obstacle in trying to quit alone is making the behavioral changes necessary to eliminate the habits associated with smoking. Excellent books, tapes, and manuals are available and are strongly recommended to help people who want to quit without other assistance.

Nicotine replacement therapy involves the use of products that provide low doses of nicotine that do not contain the contaminant found in smoke. The goal of therapy is to relieve cravings for nicotine and ease the symptoms of withdrawal.

In general, nicotine replacement therapy benefits moderate-to-heavy smokers the most. However, it does appear somewhat helpful for light smokers (people who smoke fewer than 15 cigarettes a day).

Nicotine Patches. Nicotine patches deliver nicotine through the skin. This is called transdermal nicotine delivery. It is effective in reducing symptoms during withdrawal. Nicotine patches are available over the counter.

Patches may work in different ways:

Step-Down Approach. Patches that use this method include NicoDerm CQ. The patches come in three strengths (21, 14, and 7 mg). You use the strongest dose first and reduce it gradually over a period of 8 - 10 weeks. A 21 mg patch is about equal to 15 cigarettes. A heavy smoker may need to wear two patches at first.
Single-Step Approach. The single-step patch (Nicotrol) can be taken off after 16 hours and replaced 8 hours later. It can be used for only 6 weeks.

Patches are applied and used in similar ways:

A single patch is worn each day and replaced after 24 hours.
To avoid skin irritation it is applied to different hairless locations above the waist and below the neck each day.
People can wear the patches for 24 hours, but some have reported odd dreams and have disliked the sensation of the patch during the night. People who wear the patch all the time, however, have fewer withdrawal symptoms and slightly better abstinence rates than those who take it off at night.
Patches should be stored and discarded safely, particularly in homes with small children. Small children have been poisoned and gotten sick from wearing, chewing, or sucking on nicotine patches. There have been no reports of death from children who have been poisoned.
The FDA recommends using the patches for 3 - 5 months, although some studies suggest that using them for 8 weeks achieves the maximum benefits.

Children should not come in contact with the patches, even while the smoker is wearing them. If the child has worn the patch, the affected skin should be washed right away. Urgent medical care may be required if the child has eaten nicotine or worn a patch for a prolonged time.

Nicotine Gum. Nicotine gum (Nicorette) is available over the counter and has helped many people quit. Some prefer it to the patch because they can control the nicotine dosage, and chewing satisfies the oral urge associated with smoking.

Tips for using the gum:

If you are just starting to quit, chew 1 - 2 pieces each hour. A smoker should not chew more than 20 pieces a day.
The goal is to stop using the gum by 6 months, but about 3% of people continue to use it long after they have quit smoking.
The gum must be chewed slowly until it develops a peppery taste. It is then tucked between the gum and cheek where it is stored so that the nicotine can be absorbed.
Coffee, tea, soft drinks, and acidic beverages may interfere with nicotine absorption, so people should wait at least 15 minutes after drinking before chewing a piece of gum.

Some people prefer other methods or cannot use the gum for the following reasons:

They find the gum unpleasant tasting.
Side effects specific to the gum may include upset stomach, mouth ulcers, hiccups, and throat irritation.
They are embarrassed by chewing gum.
They wear dentures.

Long-term dependence may be a problem with the gum. Although such dependence is probably safer than smoking, research is needed to confirm this, and experts recommend people chew gum for no more than 6 months.

The Nicotine Inhaler. The nicotine inhaler resembles a plastic cigarette holder. It comes with a number of nicotine cartridges, which are inserted into the inhaler and "puffed" for about 20 minutes, up to 16 times a day. The dose is gradually decreased. It requires a prescription in the United States. Several studies have reported that the inhaler triples abstinence rates (between 17 - 28%) compared with placebo (6 - 9%) after 6 months. It has some specific advantages over other nicotine replacement products:

The inhaler provides varying doses of nicotine on demand (as opposed to continuously with the patch or the gum) and is relatively fast-acting. Blood nicotine levels peak about 20 minutes after using the inhaler, comparable to the gum and faster than the 2 - 4 hours seen with the patch.
It satisfies oral urges.
Most of the nicotine vapor is delivered in the mouth, not into the lung airways (although some people experience mouth or throat irritation and cough).

Using a combination of the inhaler and the patch may be particularly effective. In one study, the combination led to an abstinence rate of over 60% after 6 weeks. While this percentage dropped off over time, it was still a large improvement over the use of the inhaler and a placebo patch.

The Nicotine Nasal Spray. The nasal spray satisfies immediate cravings by providing doses of nicotine rapidly and thus may play a useful role in conjunction with slower-acting nicotine replacement therapies. (Nicotine levels peak within 5 - 10 minutes after administering the spray). The spray can irritate the nose, eyes, and throat, so it may not be suitable for those with allergies or sinus infections. Most people, however, can tolerate the side effects, which usually go away within the first few days.

Nicotine Lozenge. A nicotine lozenge (Commit) is available over the counter. It is made from pressed tobacco and comes in two strengths for heavier or lighter smokers. In a large 2002 study, 15 - 18% of smokers who used it remained smoke free, compared to 6 - 10% who were given a dummy lozenge. Side effects included heartburn, hiccups, nausea, headaches, and cough. The Commit lozenge also contains phenylalanine, a chemical that certain people may need to avoid.

Facts about Nicotine Replacement Therapy:

Not cheating on the very first day of nicotine-replacement use increases the chance of quitting permanently by tenfold.
The more cigarettes a patient smokes, the higher the dose of nicotine replacement may be required at the start.
Adding a counseling program may boost the effect of any nicotine replacement program.
Do not smoke while using nicotine replacement. It can cause nicotine to build up to toxic levels.
Nicotine replacement helps prevent weight gain while it is being used, but people are still at higher risk for gaining weight when they stop all nicotine.

Side Effects. Side effects of any nicotine replacement product may include headaches, nausea, and other gastrointestinal problems. People often experience sleeplessness in the first few days, particularly with the patch, but the insomnia usually passes. Patients using very high doses are more likely to have symptoms. Reducing the dose can prevent them.

Special Concerns for Specific Individuals. There has been some concern that the patch might be harmful for people with heart or circulatory disease, but studies are finding that it poses no danger for these individuals. In fact, it may help reduce angina attacks brought on by exercise. However, unhealthy cholesterol levels (lower HDL levels) caused by smoking remain abnormal with use of the nicotine patch. HDL levels improve when all nicotine is stopped.

Nicotine replacement may not be completely safe in pregnant women, although it has been used successfully in this group without ill effect. There is an increase in heart rates in unborn children of women who use the patch as compared with those who smoke.

Keep all nicotine products away from children. Nicotine is a poison. All nicotine products should be kept safely away from small children. A parent should call a physician or a poison control center immediately if a child has been exposed to a nicotine replacement product, even for a short duration. Parents should also call the doctor if a small child has been exposed to a nicotine product and has any symptoms, including stomach upset, irritability, headaches, a rash, or fatigue.

Warnings Against Long-Term Use. No one should use nicotine replacement therapies as a long-term substitute for smoking. Any nicotine replacement therapy should be temporary. In one study, use of nicotine gum for more than a year was associated with insulin resistance, an abnormality that occurs in diabetes. Some studies have now suggested that nicotine itself may have properties that increase the risk for cancer, independent of carcinogenic chemicals in smoke. More studies are needed.

Bupropion (Zyban, Wellbutrin) is a type of antidepressant that is also an FDA-approved product for smoking cessation. It differs from most other antidepressants because it increases the effects of dopamine, the brain chemical that appears to play a strong role in nicotine addiction. Using Zyban along with nicotine replacement therapy may help you better control cigarette smoking cravings. Zyban does not contain nicotine. In most cases, Zyban is taken a week or two before quitting, and must be taken for 7 - 12 weeks. The usual maintenance dose is 150 mg tablet twice a day. No single dose should be higher than 150 mg.

Side effects of bupropion include gastrointestinal problems, headaches, insomnia, dry mouth, and irritation. In very rare cases, seizures have occurred, although usually in people who exceeded the recommended dose or who already had risk factors for seizures.

A newer drug called varenicline (Chantrix) may significantly reduce cigarette cravings and work better than Zyban. A study in the Archives of Internal Medicine found that almost 50% of those who took varenicline successfully quit. Varenicline mimics some effects of nicotine on the brain, but blocks others. Previous studies published in the Journal of the American Medical Association showed that Chantrix works twice as well as Zyban and quadruples one’s chances of successfully quitting. The FDA approved Chantrix as a smoking cessation aid in May 2006. It is for use in cigarette smokers age 18 and older. It should not be combined with nicotine replacement therapy.

The tricyclic antidepressant nortriptyline (Pamelor, Aventyl) may help reduce nicotine action. Quit rates with either of these medicines are as high as 30%. Long-term abstinent rates are more than twice those of placebo. Most other antidepressants, including fluoxetine (Prozac), have no additional benefits for smokers.

Nortriptyline has been specifically studied for helping smokers. It is best to start taking the medication 10 - 28 days before your intended quit date. Studies have reported quit rates of 14 - 24%. Side effects of nortriptyline include dry mouth and changes in taste. It should be noted that in rare cases, tricyclics can have serious side effects, and overdose can be deadly. Tricyclics may pose a danger for some patients with certain types of heart disease.

Smokers who use outside help have the best record for quitting, with success rates of 25 - 35%. Those who are counseled in addition to using nicotine replacement and Zyban have the best chance. Brochures, audio tapes, and other self-help materials are often ineffective when used alone, but may be helpful in conjunction with a counseling program.

Types of behavioral approaches:

Problem Solving or Coping Strategies. Smokers more likely to quit smoking when they learn thinking (cognitive) and behavioral techniques for breaking the link between certain cues and smoking, stress management techniques, and ways to handle the symptoms of withdrawal and the urge to relapse. The more intense the counseling program, the better. Smokers should look for programs that offer the following:

Session lengths of 20 - 30 minutes
Four to seven sessions
A 2-week program
Additional 2 weeks or more of follow-up contact

Scheduled Reduction. Scheduled reduction is a gradual way to stop smoking.

Divide the number of minutes per day that you are awake by the number of daily cigarettes you smoke. The number you get is how long you wait between smokes.
Week 1: Set up a schedule with time intervals based on this result and using a timer, smoke only at those intervals. If the "cigarette appointment" is missed by more than 5 minutes, you must skip that cigarette.
Week 2: Reduce the number of cigarettes you smoke by one-third and recalculate your time between smokes based on the lower number.
Week 3: Reduce the count again.
Week 4: Quit smoking

Those who are unable to smoke during working hours could try calculating the intervals based on the usual smoking times of the day.

The Staged Approach. The intent of the staged approach is to plan quitting interventions customized for each individual rather than imposing some general method for quitting. The approach takes the smoker through six stages with behavioral interventions at each point:

Pre-contemplation
Contemplation
Preparation
Action
Maintenance
Termination

Although some studies report this approach is significantly more effective than non-staged methods, an analysis of 23 trials did not find the staged approach to be any more effective than other methods. Most studies, however, were weak, and better research is needed on this approach.

People who follow this approach do not proceed from one stage to another in a simple, step-by-step fashion. They actually cycle or spiral back and forth, so that they may move from stage 1 to 2 to 3, and then back to 2 again. They may stay in maintenance mode for years and then fall back to stage 2. Remember that this is normal -- if you tried quitting in the past and didn't stick with it, don't consider yourself a failure. Just try again.

Stage 1: Pre-Contemplation.

People at this stage have no plans or desire to stop smoking. They aren't even considering quitting. People at this stage are generally unaware of the specific benefits that quitting can bring. Or, they may simply have "failed" in the past and have given up. There's no point in talking about how to start a cessation program at this stage. Instead, it is important to think about how quitting will help you feel better, have more confidence, or live longer. The benefits must be identified before a person will consider quitting. If you are at this stage, a good activity is to ask several friends or family members why they quit.

Stage 2: Contemplation.

A person at this stage is thinking, "I think I should probably quit, but I need help getting started." People at this stage know that quitting is good for them, but it seems like a daunting task or they don't think they can pull it off. Some may have tried and failed in the past. It's important for people at this stage to consider some of the truths and falsehoods of quitting. If you are at this stage, write down (brainstorm) all your potential roadblocks -- the things that you believe make quitting difficult -- and learn strategies for overcoming or side-stepping those hurdles. People at this stage might benefit from making a pledge, contract, or other commitment that they are going to get more active in the near future. The goal is to identify the roadblocks and ways to overcome these hurdles, and make a commitment to quitting.

Stage 3: Preparation.

Smokers at this stage are ready to quit. The goal of this stage is to create a specific action plan that takes all factors into account, so that quitting is successful. People at this stage need to know what methods work and what support exists to help them. If you are at this stage, you should consider some backup plans -- what to do when the urge to smoke hits you.

Stage 4: Action!

People at this stage have just quit. This stage is where the most behavioral change occurs. It requires significant commitment and energy. If you are at this stage, keep talking to friends and family for inspiration. Review your backup plans. Reward yourself for small achievements. Having a fellow smoker quit with you can be a huge support as you both get through this stage.

Stage 5: Maintenance.

People at this stage have been smoke-free at least 6 months. The goal now is to prevent relapse. If you are at this stage, continue to be wary of roadblocks and keep reminding yourself of the benefits you have gained. Think about what you have found most enjoyable about being smoke-free.

Hypnosis. Although rigorous studies are lacking, some people report successful cessation from smoking when hypnosis is given in individual sessions. The process is effective only if you trust the therapist and can feel completely at ease in the vulnerable and passive state necessary for hypnotic suggestion.

During a typical session, the hypnotherapist will use various techniques (such as imagery, silent counting) to put you in a relaxed state.

When you are very relaxed, but not asleep, the hypnotherapist quietly suggests motivations for not smoking. The hypnotherapist should also reinforce a positive self-image while you are in deep relaxation. This helps many people avoid the depression that accompanies withdrawal.

The sessions usually takes about 1 hour.

You should be taught methods of self-hypnosis to use at home, and follow-up once to reinforce what you've learned.

Acupuncture and Acupressure. The acupuncture technique for quitting smoking usually uses very tiny curved staples inserted into three different points around the edge of the ear. The procedure is painless. You will be told to press each staple in a certain order for a few seconds whenever the craving for a cigarette occurs. The acupuncturist may also use acupuncture points elsewhere on the body. There are no side effects except for some soreness if the acupuncture staple is pressed too hard.

A related technique called acupressure involves simply pressing select points on the body when a craving hits. Some studies have reported good quit rates with acupuncture, but few rigorous studies have been conducted using this approach.

Aim to Quit Completely

Everyone who quits should aim to quit completely. Most people who return to smoking "cheat" in the first few weeks. Quitting completely is essential to regain good health and reverse bad effects caused by smoking. Reducing smoking, even by half, does not eliminate the risk for cancer and other health problems. Although smokers take in less smoke and nicotine, the body is still unable to heal itself from the ongoing intake of toxins. It should also be noted that changing to low-tar cigarettes is not a solution. In fact, smokers of these cigarettes tend to inhale deeper, perhaps even increasing health risks.

Create a List

Write down 10 reasons to quit. In addition to health reasons, the list might include having better smelling hair, clothes, and breath; having fewer wrinkles; enjoying the taste of food; and saving money. Read the list often during the quitting process to help stay motivated.

Decide on a Specific Quit Date

Some people find it helpful to choose a particular date to quit when little or no stress is anticipated for at least the first 3 days. Women affected by PMS should avoid quitting right before their menstrual cycle. It may help to write out a quit contract, putting the date on paper, and getting a friend to sign it. Discard all smoking paraphernalia on the eve before the quit date, and make plans to stay busy on the day itself, and especially at night, when the urge to smoke will be high.

Make an Oath

Take an extreme oath. For example, "If I smoke one more cigarette my dog will die." Although this seems absurd, some people, even well-educated individuals, who have failed all other methods have reported that they quit completely and successfully after taking such an oath.

Let the Body and Mind Heal During Withdrawal

Retreat from the world when cravings become overwhelming. Take naps, warm baths or showers, meditate, or read novels.
Help your body get rid of nicotine. Drink plenty of water, eat fresh fruits, vegetables, whole grains, and fiber-rich foods. Carrots, apples, and celery are good munching foods.
When cravings occur, hold your breath as long as possible or take a few deep rhythmic breaths.
Use meditation or relaxation and deep breathing exercises. In fact, taking deep breaths when the urge to smoke occurs is a good stopgap measure.

Get Family and Friends Involved

Tell all your friends and family that you've already quit, so you'll be embarrassed if they catch you smoking.
Pay a family member or friend if they catch you smoking. The amount should be large enough ($5 - 20) to be a deterrent, but not so large as to be ridiculous.
If your partner or friend smokes, try persuading them to quit or, at the very least, not to smoke around you and others.

Exercise

Studies continue to show that smokers who exercise can greatly increase their ability to quit smoking while reducing their risk for weight gain. Move the muscles when cravings occur. Dance, run, walk, jump up and down, stretch, do push-ups. Yoga is an excellent exercise program for quitting. Older people and anyone with health problems should consult their health care provider before starting such a program.

Maintain a Healthy Diet

Eat plenty of fresh, crunchy fruits and vegetables. This is also a useful way of satisfying oral cravings without adding many calories.
Drink plenty of water and healthy beverages.
Moderate intake of coffee or tea may be helpful. A small study suggested that drinking caffeinated beverages (such as coffee or tea) while on nicotine replacement may enhance energy expenditure and may help prevent weight gain. Moderate coffee intake may also have antidepressant properties. Avoid caffeine in the evening, however, since sleep disturbances can be a problem during withdrawal.

Change Daily Habits

Change your daily schedule, particularly eating times, as much as possible. Eat at different times or eat many small meals instead of three large ones. Sit in a different chair or even a different room.
If you smoke after eating, find other ways to end a meal. Play a tape or CD, eat a piece of fruit, get up and make a phone call, or take a walk (a good distraction that burns calories as well). For example, if you normally have a cigarette with coffee, drink tea instead or use a different cup.
Substitute oral habits by eating celery, chewing sugarless gum, sucking on a cinnamon stick, or carrying worry beads.
Go to public places and restaurants where smoking is prohibited or restricted.
Set short-term quitting goals and reward yourself when they are met.
Every day put the money normally spent on cigarettes in a jar and buy something pleasurable at the end of a predetermined period of time.
Find activities that focus the hands and mind but are not taxing or fattening: Computer games, solitaire, knitting, sewing, whittling, and crossword puzzles.

Denormalization is the idea that smoking is no longer normal. This concept of denormalization is best instituted by laws and local regulations making smoking inaccessible in public places, raising prices, and putting stricter limitations on cigarette advertising.

Increasing taxes on cigarettes may be one of the most important methods for reducing smoking in the population, particularly in younger people.

Evidence is suggesting that banning smoking in work and public places may be leading to a higher quit rate than in places where smoking is permitted.

Denormalization can also work on a personal level. A British study showed that when one spouse makes healthy changes, including quitting smoking, the other one follows. In couples where smoking continues, it usually continues in both.

Symptoms of Withdrawal

After you quit smoking, you with have some withdrawal symptoms. Such symptoms generally peak in intensity 3 -5 days after you quit, and usually disappear after 2 weeks, although some may persist for several months.

The symptoms of withdrawal include both physical and mental difficulties.

Physical Symptoms.

Tingling in the hands and feet
Sweating
Intestinal disorders (cramps, nausea)
Headaches
Sore throat, coughing, and signs of a cold

Withdrawal symptoms should be treated accordingly, just as you would with physical symptoms due to an illness or disease.

Mental and Emotional Symptoms. Tension and craving build up during periods of withdrawal, sometimes to a nearly intolerable point. Nearly every moderate-to-heavy smoker experiences more than one of the following strong emotional and mental responses to withdrawal:

Temper tantrums, intense needs, feelings of dependency, and a state of near paralysis
Insomnia
Mental confusion, vagueness, or difficulty concentrating
Irritability, restlessness, impatience, or anger
Anxiety
Depression

The first signs of nicotine withdrawal seem to appear within 30 minutes of a smoker’s last cigarette. The findings, published in Psychopharmacology, are believed to be the first to show just how early nicotine withdrawal occurs. The study involved 50 people who smoked a pack of cigarettes daily. Half refrained from smoking for 4 hours, while the others smoked as usual. After 30 minutes, those who did not have a cigarette craved one and did more poorly on tasks requiring attention than those in the smoking group. Within 3 hours, the non-smoking group showed increases in anxiety, sadness, and difficulty concentrating.

Depression is common during withdrawal and over the long term. In the short term, it may mimic the feelings of grief felt when a loved one is lost. A smoker should plan on a period of actual mourning in order to get through the early withdrawal depression.

Smoking may be masking depression, which can become severe even after the early stages of withdrawal have passed.
For some smokers, the future physical damage incurred by smoking is an abstraction, which fails to motivate quitting when measured up against the very real emotional pain triggered by nicotine withdrawal.
Not only does the smoker suffer, but the negative emotions often harm relationships with friends and family, who might even urge the ex-smoker to take up cigarettes again.

People who suffer from depression while quitting might do better using a combination of emotionally supportive therapy (as opposed to behavioral therapy), nicotine replacements, and antidepressants, such as bupropion (Zyban). If severe depression lasts beyond the withdrawal period, professional help should be sought as soon as possible.

Quitting smoking does increase the risk for weight gain. But, kicking the habit of smoking may cause more weight gain than previously thought. A study in Health Services Research found that the average weight gain among former smokers was about 21 pounds, rather than the 5 - 15 pounds commonly cited. But, fear of weight gain shouldn’t stop a person from quitting smoking. Instead, the study authors encourage weight-control measures after quitting. To come up with a new average, the scientists re-analyzed data from the 1998 Lung Health Study of 5,887 American smokers. That study found that those who quit smoking gained about 12 pounds.

Smoking uses up calories -- about 200 a day according to one study. Burning calories helps you lose weight. After quitting, the body's metabolism slows down, and food is digested better. Insulin levels increase, enabling the body to process more sugar for energy. When you quit smoking, you may snack more frequently.

How to Keep the Weight Off After Smoking. Exercise is very helpful in controlling weight. To burn the same amount of calories as you did while smoking, you need only take an extra 15-minute daily walk and eliminate 100 calories a day from meals. Just a moderate increase in physical activity can help keep weight gain to a minimum.

Nicotine replacement therapy can help protect against weight gain. See the section on "Quitting Smoking" in this report.

Failure to Quit

Biologic, psychological, behavioral, and cultural factors all play a role in nicotine addiction, making smoking one of the hardest addictions to beat. About half of people who quit return to smoking. Even after years of not smoking, some ex-smokers still have occasional cravings for cigarettes.

Some experts suggest that, in addition to depression, there are three major areas responsible for the inability to quit:

Mental performance. Nicotine improves concentration and thinking. Quitting smoking temporarily impairs one's mental performance.
Stress. Although smoking many not reduce stress, stopping certainly increases it.
Weight gain. Quitting smoking can cause you to gain weight. Studies are mixed on whether weight gain is permanent in most smokers or not. Certainly, it is a major factor in relapse. [See "Weight Gain" section in this report.]

How well a person does in the first 2 weeks is critical to their success. Smokers should not be shy about seeking all the help they can during this period. Although withdrawal symptoms can be intense, treatments are available to reduce them.

Attempts to quit are never a waste of time, since the amount of smoking is reduced during these periods. People who keep trying still have a 50 - 50 chance of finally quitting.

Researchers have been trying to discover individual risk factors or sets of behaviors that can help predict why specific people fail to quit. Some factors include:

Being female
Being a heavy smoker
Inhaling deeply
Being a long-term smoker
Having severe withdrawal symptoms

Among many studies, however, only one found a single consistent factor for failure to quit:

Cheating during the first 2 weeks of withdrawal, even with the patch, nearly guarantees that a person will smoke again in 6 months.

Studies show that women have a harder time trying to quit smoking and have less success with abstinence programs than men. There are many proposed reasons for this:

Nicotine has different effects on mood in women compared to men. Women who quit may have greater anxiety and stress than men who quit.
Women are not as physically dependent on nicotine as men, but they are more addicted to the actual behavior of smoking, which is the more powerful deterrent to quitting. This may be the reason why nicotine replacement, which only reduces cravings, tends not to be as effective in women.
Women may fear weight gain after quitting more than men.
Certain phases in the menstrual cycle may reduce the response to drugs that are used to help women quit smoking.
Men may be less supportive than women in helping their partners to quit.
Women trying to quit may miss the feeling of control associated with smoking more than men.

On the positive side, evidence suggests that when women quit, their lung function seems to improve more rapidly than in men who quit.

Lifestyle Changes

Smokers and former smokers should immediately begin to implement a healthier lifestyle and change any other behaviors that might be damaging their health.

Everyone should also maintain a healthy diet, with foods rich in whole grains and fruits and vegetables (particularly dark colored ones). Avoid saturated fats and instead choose monounsaturated fats, which are found in olive oil or fats from oily fish. Two studies have indicated that eating fish more than twice a week might help limit the tobacco damage in people who do not smoke more than a pack and a half a day.

Even with a healthful diet, however, smoking reduces the levels of a number of vitamins, importantly vitamin C. Some research suggests that supplementation of folic acid, a B vitamin, and the antioxidants vitamins E and C and selenium may improve lung function or reduce the damage done by cigarette smoke. Studies have shown that daily vitamin E supplements are associated with reduced risk for prostate cancer among smokers and that higher levels of vitamin E are linked to a lower risk for lung cancer. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see an image of the benefits of vitamin E.

Click the icon to see an image of the sources of vitamin E.

Women who are pregnant and continue to smoke must be sure to take appropriate vitamins, particularly folic acid. In this way, they might reduce the increased risk of fetal injury and death, although they do not eliminate that risk.

Regular exercise reduces a smoker's risk of heart disease (although still not to the level of a nonsmoker). Exercise does not lower a smoker's risk for lung cancer or emphysema.

If you smoke, you should be screened for any smoking-related disorders. Have your cholesterol and blood pressure checked regularly. Women should have annual Pap smears to detect cervical cancer. All older adults should be screened for colon cancer. Computed tomography (CT) screening programs, which are becoming increasingly available, may detect lung cancer at an early stage. Ask your health care provider if you should have this test, and if your insurance will cover it.

Resources

www.cancer.org -- American Cancer Society
www.lungusa.org -- The American Lung Association

References

Alati R, Al Mamun A, O'Callaghan M, Najman JM, Williams GM. In utero and postnatal maternal smoking and asthma in adolescence. Epidemiology. 2006 Mar;17(2):138-44.

Amin S, Niu J, Guermazi A, et al. Cigarette smoking and the risk for cartilage loss and knee pain in men with knee osteoarthritis. Ann Rheum Dis. 2007 Jan;66(1):18-22. Epub 2006 Dec 7.

Breslau N., Novak SP, Kessler RC. Psychiatric disorders and stages of smoking. Biological Psychiatry. 55(1):69-76, 2004.

Centers for Disease Control and Prevention (CDC). Tobacco use among adults -- United States, 2005. MMWR. 2006 Oct 27;55(42):1145-8.

Centers for Disease Control and Prevention (CDC). Annual smoking-attributable mortality, years of potential life lost, and productivity losses -- United States, 1997-2001. MMWR. 2005;54:625-628.

Centers for Disease Control and Prevention (CDC). State-specific prevalence of smoke-free home rules -- United States, 1992-2003. MMWR. 2007 May 25;56(20):501-4.

Chaudhuri R, Livingston E, McMahon AD, et al. Effects of smoking cessation on lung function and airway inflammation in smokers with asthma. Am J Respir Crit Care Med. 2006 Jul 15;174(2):127-33.

Dobson R. Smoking may increase abdominal obesity. BMJ. 2005 Sep 17;331(7517):596.

Eisenberg D, Quinn BC. Estimating the effect of smoking cessation on weight gain: an instrumental variable approach. Health Services Research. 2006 July 6; (early online version).

Galatz LM, Silva MJ, Rothermich SY, Zaegel MA, Havlioglu N, Thomopoulos S. Nicotine delays tendon-to-bone healing in a rat shoulder model. J Bone Joint Surg Am. 2006 Sep;88(9):2027-34.

Health, United States, 2005, with Chartbook on Trends in the Health of Americans. Hyattsville, Md. National Center for Health Statistics; 2005.

Hendricks P, Ditre J, Drobes D, Brandon T. The early time course of smoking withdrawal effects. Psychopharmacology. 2006;187(3): 385-396.

Houston TK, Person SD, Pletcher MJ, Liu K, Iribarren C, Kiefe CI. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ. 2006 May 6;332(7549):1064-9.

Linn-Rasker SP, van der Helm-van Mil AHM, van Gaalen FA, et al. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis. 2006;65:366-371.

Li YF, Langholz B, Salam MT, Gilliland FD. Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Chest. 2005 Apr;127(4):1232-41.

Mennella JA, Yourshaw LM, Morgan LK. Breastfeeding and smoking: short-term effects on infant feeding and sleep. Pediatrics. 2007 Sep;120(3):497-502.

Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007 Jan 26;315(5811):531-4.

Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8.

Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, Anziano R, Reeves K. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006 Aug 14-28;166(15):1571-7.

Ritz B, Ascherio A, Checkoway H, et al. Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol. 2007 Jul;64(7):990-7.

Sargent JD, Stoolmiller M, Worth KA, et al. Exposure to smoking depictions in movies: its association with established adolescent smoking. Arch Pediatr Adolesc Med. 2007 Sep;161(9):849-56.

Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006 Aug 19;368(9536):647-58.

The Health Consequences Of Smoking: A Report Of The Surgeon General. Atlanta, GA: US Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, US Dept of Health and Human Services; 2004.

Tonnesen P, Mikkelsen K, Bremann L. Nurse-conducted smoking cessation in patients with COPD using nicotine sublingual tablets and behavioral support. Chest. 2006 Aug;130(2):334-42.

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Review Date:
10/8/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

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

Epilepsy

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

In This Report

Highlights
Introduction
Causes
Outlook and Effects
Diagnosis
Treatment
Treatment After The First S...
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved levetiracetam (Keppra) for treatment of primary generalized tonic-clonic seizures in adults, and children ages 6 years and older, who have idiopathic generalized epilepsy. Levetiracetam was previously approved for partial-onset seizures and myoclonic seizures.

Carbamazepine and Genetic Testing

In 2007, the FDA recommended that patients of Asian ancestry get a genetic test prior to taking carbamazepine (Tegetrol, Equetro, Carbatrol). Rare, but serious, side effects of carbamazepine include life-threatening skin reactions such as Stevens-Johnson syndrome. The risk for these skin reactions is significantly higher for patients of Asian ancestry. A simple blood test can check for the presence of a genetic mutation that increases this risk. Patients who test positive for this gene should not take carbamazepine unless the benefits clearly outweigh the risks.

Epilepsy and Suicide Risk

People with epilepsy have a high risk for suicide, especially within 6 months of diagnosis, suggests a 2007 study in Lancet Neurology. The researchers found that suicide risk was especially high for people who have both epilepsy and another psychiatric condition (such as depression, anxiety, schizophrenia, or alcoholism). The researchers recommend that doctors carefully monitor newly diagnosed patients.

Ketogenic Diet

The ketogenic diet, which is characterized by high fat and low carbohydrate intake, is resurging in popularity for the treatment of children with difficult-to-control seizures, according to a 2007 review in Pediatrics. The ketogenic diet helps stop or reduce seizures in about a third of children. The diet is complex. Parents should seek supervision and guidance from a doctor or trained health professional.

Introduction

Epilepsy is characterized by unprovoked, recurring seizures that disrupt the nervous system and can cause mental and physical dysfunction. In the U.S., about 2.5 million people are affected by epilepsy and seizures. About 10% of the American population will experience at least one seizure during their lifetime.

The structures of the brain include: the brainstem, consisting of the spinal cord, the medulla oblongata, the pons and the midbrain; the cerebellum; the cerebrum (one half, or hemisphere shown); and the diencephalon.

Epilepsy affects all age groups. Males have a slightly higher risk than females. The incidence is highest in children, with another, but lesser, peak occurring after age 60. According to one estimate, 14% of epilepsy patients are under 15 years old, and about 25% are over age 64.

Every year, 25,000 - 40,000 American children have a first seizure that is unrelated to a fever. Epilepsy is decreasing in childhood but increasing in the elderly, probably because of mild strokes and cardiac arrest.

Epilepsy is not a single disorder but rather a wide spectrum of problems. What all types of epilepsy share are recurrent, unprovoked seizures caused by an uncontrolled electrical discharge from nerve cells in the cerebral cortex. This part of the brain controls higher mental functions, general movement, and the functions of the internal organs in the abdominal cavity, perception, and behavioral reactions.

Seizures are a symptom of epilepsy. Epilepsy types are generally put into two categories, which are based on the specific biologic mechanisms involved in the seizure and the anatomical location of the seizure. The two types are:

Partial (also called focal or localized) seizures. These seizures are more common than generalized seizures and occur in one or more specific locations in the brain. In some cases, partial seizures can spread to wide regions of the brain. They are likely to develop from specific injuries, but in most cases the exact origins are unknown.
Generalized seizures. These seizures typically occur in both sides of the brain. Many forms of these seizures are genetically based. There is usually normal neurologic function.

Experts are finding, however, that these categories do not actually reflect what is now known about the brain's anatomy. For example, the words "partial" and "generalized" suggest that seizures either involve only part of the brain or are widespread. However, a number of events in the brain occur with either type, muddying these distinctions. Researchers are now in the process of making clearer definitions and terms that reflect what actually is happening in the brain.

New classification systems better define specific epilepsies. Some professional groups now suggest that epilepsies be classified in the following five ways:

Type of seizure (partial or generalized)
Description of the seizure onset and evolution
Specific syndromes that are associated with one or more seizure types (however, not all seizures will be part of a syndrome)
Specific causes of the seizures, if known
Degree of impairment

These seizures are subcategorized as "simple" or "complex partial."

Simple Partial Seizures. A person with a simple partial seizure (sometimes known as Jacksonian epilepsy) does not lose consciousness, but may experience confusion, jerking movements, tingling, or odd mental and emotional events. Such events may include deja vu, mild hallucinations, or extreme responses to smell and taste. After the seizure, the patient usually has temporary weakness in certain muscles.
Complex Partial Seizures. Slightly over half of seizures in adults are complex partial type. About 80% of these seizures originate in the temporal lobe, the part of the brain located close to the ear. Disturbances there can result in loss of judgment, involuntary or uncontrolled behavior, or even loss of consciousness. They may lose consciousness briefly and appear to others as motionless with a vacant stare. Emotions can be exaggerated; some sufferers even appear to be drunk. After a few seconds, a patient may begin to perform repetitive movements, such as chewing or smacking of lips. Episodes usually last no more than 2 minutes. They may occur infrequently, or as often as every day. A throbbing headache may follow a complex partial seizure.

In some cases, simple or complex partial seizures evolve into what are known as secondarily generalized seizures. The progress may be so rapid that the partial stage is not even noticed.

While the term "partial" implies the seizures affect only small or specific brain locations, in reality, they almost always involve diffuse and even widespread areas. In the future, the term "focal seizures" will most likely replace the term "partial seizures," and its subcategories. Until new classifications are more widely in use, this report will continue to use the term "partial seizures" and its subcategories.

Generalized seizures are caused by nerve cell disturbances that occur in more widespread areas of the brain than do partial seizures. Therefore, they have a more serious effect on the patient. They are further subcategorized as tonic-clonic (or grand mal) or absence (petit mal) seizures.

Tonic-Clonic (Grand Mal) Seizures. The first stage of a grand mal seizure is called the tonic phase, in which the muscles suddenly contract, causing the patient to fall and lie stiffly for about 10 - 30 seconds. Some people experience a premonition or aura before a grand mal seizure. Most, however, lose consciousness without warning. If the throat or larynx is affected, there may be a high-pitched musical sound (stridor) when the patient inhales. Spasms occur for about 30 seconds to 1 minute. Then the seizure enters the second phase, called the clonic phase. The muscles begin to alternate between relaxation and rigidity. After this phase, the patient may lose bowel or urinary control. The seizure usually lasts a total of 2 - 3 minutes, after which the patient remains unconscious for a while and then awakens to confusion and extreme fatigue. A severe throbbing headache similar to migraine may also follow the tonic-clonic phases.
Absence (Petit Mal) Seizures. Absence or petit mal seizures are brief losses of consciousness that occur for 3 - 30 seconds. Physical movement and loss of attention may stop for only a moment. Such seizures may pass unnoticed by others. Small children may simply appear to be staring or walking distractedly. Petit mal may be confused with simple or complex partial seizures, or even with attention deficit disorder. [See In-Depth Report #30: Attention deficit hyperactivity disorder.] In petit mal, however, a person may experience attacks as often as 50 - 100 times a day. About 25% of patients with petit mal develop grand mal seizures. An electroencephalogram (EEG) test that shows a specific brain wave pattern can usually identify these patients.

Click the icon to see a depiction of a tonic-clonic seizure.

Atonic (Akinetic) Seizures. A person who has an atonic (or akinetic) seizure loses muscle tone. Sometimes it may affect only one part of the body so that, for instance, the jaw slackens and the head drops. At other times, the whole body may lose muscle tone, and the person can suddenly fall. A brief atonic episode is known as a drop attack.

Simply Tonic or Clonic Seizures. Seizures can also be simply tonic or clonic. In tonic seizures, the muscles contract and consciousness is altered for about 10 seconds, but the seizures do not progress to the clonic or jerking phase. Clonic seizures, which are very rare, occur primarily in young children, who experience spasms of the muscles but not tonic rigidity.

Myoclonic. Myoclonic seizures are a series of brief jerky contractions of specific muscle groups, such as the face or trunk.

Epilepsy is also grouped according to a set of common characteristics, including:

Patient age
Type of seizure or seizures
Whether a cause is known or not (idiopathic)

A few syndromes and inherited epilepsies are listed as follows. They do not represent all epilepsies.

West Syndrome (Infantile Spasms). West syndrome, also called infantile spasms, is a disorder that involves spasms and developmental delay in children within the first year, usually in infants ages 4 - 8 months.

Benign Familial Neonatal Convulsions. Benign familial neonatal convulsions (BFNC) are a rare, inherited form of generalized seizures that occur in infancy. BFNC appears to be caused by genetic defects that affect ion channels in nerve cells that carry potassium.

Juvenile Myoclonic Epilepsy (Impulsive Petit Mal). Juvenile myoclonic epilepsy, also called impulsive petit mal epilepsy, is characterized by generalized seizures, usually tonic-clonic marked by jerky movements (called myoclonic jerks), and sometimes absence seizures. This accounts for 7% of epilepsies, and usually occurs in individuals ages 8 - 20.

Adult Myoclonic Epilepsy. Some research suggests that adult myoclonic epilepsy may be a previously un-described and distinct syndrome. It involves the development of generalized epilepsy of unknown causes in middle-aged adults.

Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome is a severe form of epilepsy in young children that causes multiple seizures and some developmental retardation. It usually involves absence, tonic, and partial seizures.

Myoclonic-Astatic Epilepsy. Myoclonic-astatic epilepsy (MAE) is a combination of myoclonic seizures and astasia (a decrease or loss of muscular coordination), often resulting in the inability to sit or stand without aid.

Progressive Myoclonic Epilepsy. Progressive myoclonic epilepsy is an inherited disorder occurring in children ages 6 - 15. It usually involves tonic-clonic seizures and marked sensitivity to light flashes. Although the disease was previously considered to be progressive throughout life, current therapies have significantly improved its outlook.

Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare, inherited syndrome that usually occurs during childhood, typically around age 11. However, onset varies widely within families. Seizures can be dystonic (twisting contractions) or tonic (muscle contractions), or involve thrashing. They are brief, frequent, and occur in clusters during the night. The seizures often subside with age. ADNFLE appears to be caused by an alteration in the brain receptor neuronal nicotinic acetylcholine,

Landau-Kleffner Syndrome. Landau-Kleffner syndrome is an epileptic condition that results in the inability to communicate either with speech or by writing (aphasia).

Contactin-Associated Protein-Like 2 (CASPR2) Epilepsy. CASPR2 is associated with a childhood epilepsy and autism disorder found in closely related relatives in Amish communities.

Status epilepticus (SE) is a serious, potentially life-threatening, condition that can lead to chronic epilepsy. It occurs in 100,000 - 150,000 people in the U.S. each year, over half of whom are children. Permanent brain damage or death can result if the seizure is not treated effectively.

The condition is defined as recurrent convulsions that last for more than 20 minutes and are interrupted by only brief periods of partial relief. Although any type of seizure can be sustained or recurrent, the most serious form of status epilepticus is the generalized convulsive or tonic-clonic type. In more than a third of cases, status epilepticus occurs with the first seizure. The trigger is often unknown, but can include the following:

Failure to take anti-epileptic medications (accounts for about a third of status epilepticus events)
Abrupt withdrawal of certain anti-epileptic drugs, particularly barbiturates and benzodiazepines
High fever
Poisoning
Electrolyte imbalances (imbalance in calcium, sodium, and potassium)
Cardiac arrest
Stroke. In one study, about 9% of stroke patients with seizures had status epilepticus, which resulted in higher disability after the stroke, particularly if these severe seizures occurred within a week of the stroke
Low blood sugar in people with diabetes
Central nervous system infection
Brain tumor
Alcohol withdrawal

Causes

The cause of a seizure is determined in about 28% of partial epilepsy patients. In the rest, however, epilepsy is deemed idiopathic, which means that the cause is unknown. The age of seizure onset can sometimes offer a clue. Idiopathic epilepsy is rare in children and young adults.

Epileptic seizures are triggered by abnormalities in the brain that cause a group of nerve cells in the cerebral cortex to become activated simultaneously, emitting sudden and excessive bursts of electrical energy. A seizure's effect depends on the location in the brain where this electrical hyperactivity occurs. Effects range from brief moments of confusion to minor spasms to loss of consciousness.

Click the icon to see an animation about the nervous system.

Ion Channels. Sodium, potassium, and calcium act as ions in the brain. They produce electric charges that must fire regularly in order for a steady current to pass from one nerve cell in the brain to another. If the ion channels that carry them are genetically damaged, a chemical imbalance occurs. This can cause nerve signals to misfire, leading to seizures. Abnormalities in the ion channels are believed to be responsible for absence and many other generalized seizures.

Neurotransmitters. Abnormalities may occur in neurotransmitters, the chemicals that act as messengers between nerve cells. Three neurotransmitters are of particular interest:

Gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.
Serotonin's role in epilepsy is also being studied. Serotonin is a brain chemical that is important for well-being and associated behaviors (eating, relaxation, sleep). Imbalances in serotonin are also associated with depression.
Acetylcholine is a neurotransmitter that is important for learning and memory.

Dozens of genetic syndromes representing a variety of seizure patterns may account for the different forms epilepsy.

A genetic cause has been identified for at least some cases of juvenile myoclonic epilepsy, which represents 10% of all epilepsy cases. (Such research and other studies have pointed to the GABA signaling system as an important player in many cases of epilepsy.)

Febrile seizures are caused by high fever. They usually occur in children ages 3 months to 5 years. Between 10 - 15% of children with epilepsy have a history of febrile seizures before they develop epilepsy. However, febrile seizures are quite common and occur in about 3% of all children under 5 years old. Nearly all are brief and have no long-lasting effect.

In young children, high fever from a vaccination can, in rare instances, trigger seizures. These seizures are almost always temporary and have no serious consequences.

Some controversy arose a few years ago over the possibility that the DTP (diphtheria-tetanus-pertussis) vaccine might trigger epilepsy or other neurologic diseases. Some experts suggest that children who have neurologic events following their DTP shot already have a preexisting impairment such as epilepsy, which is revealed, but not caused by, the vaccine. Children with existing epilepsy may be at risk for seizures 2 or 3 days after the vaccination. Infants with suspected neurologic problems may have their vaccinations delayed until their neurologic situation is clarified, but not beyond their first birthday. Also, a newer version of the DTP vaccine does not contain a live virus and so reduces the risk of any seizure.

Brain Tumors. Both cancerous and noncancerous brain tumors can cause seizures in all patients.

Hydrocephalus and Shunts. Hydrocephalus occurs when cerebrospinal fluid (CSF) accumulates in the brain, leading to excessive swelling of the brain ventricles. The resulting pressure can damage the brain's tissue. Hydrocephalus itself is not commonly known to cause seizures, but its treatment, which involves insertion of a shunt, may cause them. The shunt is a device that drains the excess fluid from the brain. Up to half of children who receive shunts may experience epileptic seizures, particularly if the shunt is placed before 2 years of age. More research on its relationship to epileptic seizures is needed.

Focal Cortical Dysplasia. This is an abnormality in fetal development in which the normal migration of nerve cells is altered. It can cause very severe epilepsy that is difficult to treat.

Hippocampal Sclerosis. Hardened tissue (sclerosis) in the brain's hippocampus is the most commonly identified abnormality in patients with partial epilepsy. Such abnormal brain tissue leads to structural reorganization, and both the loss and regeneration of nerve cells.

Cavernous Angiomas. Cavernous angiomas are blood vessels that grow abnormally and, like a tumor, can put pressure on nerve tissue.

Other Causes of Seizures in Children. Seizures in infants and children may be due to birth defects, difficulties during delivery, or poisoning.

Alcohol Abuse. Alcohol abuse is one of the most common causes of adolescent- and adult-onset seizures. Seizures, nearly always generalized tonic-clonic, occur in about 10% of adults during withdrawal. Multiple seizures happen in about 60% of these patients. The first seizure occurs 7 hours to 2 days after the last drink, and the time between the first and last seizure is usually 6 hours or less. [For more information, see In-Depth Report #56: Alcoholism.]

Sudden withdrawal from certain antianxiety or antidepressant drugs such as benzodiazepines, barbiturates, and tricyclic antidepressants can also contribute to seizures.

Head Injuries in Adults. Head injuries to adults can cause seizures, with the risk highest in severe head trauma. A first seizure related to the injury can occur years later, but only very rarely. People with mild head injuries, which involve loss of consciousness for fewer than 30 minutes, have only a slight risk that lasts up to 5 years after the injury.

Head Injuries in Infants and Children. Infants are at high risk for head trauma, and the severity of injury may be difficult to determine. The risk of even one seizure is generally only a concern after severe head trauma. Most children who have had a minor or not very serious head injury do not need to have medications to prevent seizures, especially when an evaluation in the emergency department was unnecessary.

Stroke. Seizure is a symptom of a major stroke. Even injury to the brain from small strokes may cause seizures. Patients who have had a severe stroke are 5 times more likely to develop epilepsy than patients who have had a mild stroke.

Seizures in adults can also be caused by:

Low blood sugar (hypoglycemia), a complication of diabetes in both children and adults.
Medications such as theophylline, meperidine, tricyclic antidepressants, phenothiazines, lidocaine, quinolones, penicillins, selective serotonin re-uptake inhibitors, isoniazid, antihistamines, cyclosporine, interferons, cocaine, lithium, amphetamines, and alcohol (withdrawal).
Occupational exposure to environmental triggers. High exposure to certain chemicals has been linked with seizures.
Alzheimer's or other degenerative brain diseases in the elderly.
Infections of the brain and central nervous system such encephalitis and meningitis.

The organs of the central nervous system (brain and spinal cord) are covered by three connective tissue layers called the meninges. They consist of the pia mater (closest to the CNS structures), the arachnoid, and the dura mater (farthest from the CNS). The meninges help support blood vessels and contain cerebrospinal fluid. The structures are involved in meningitis, an inflammation of the meninges, which, if severe, may become encephalitis, an inflammation of the brain.

Between 20 - 45% of cases of untreatable seizures have a psychologic rather than physical origin. In this form of epilepsy, known as pseudoepilepsy or psychogenic epilepsy, the patient has no conscious intent of forcing a seizure and does not show unusual emotional behavior or signs of hysteria. It is very difficult to treat and can be very disabling. Pseudoepilepsy can usually be distinguished from true epilepsy using an electroencephalogram (EEG), which measures brain waves. The cause of pseudoepilepsy is unknown.

Outlook and Effects

Most patients can control their seizures with a single drug and stop drug treatment completely after 2 years without seizures. In fact, patients who respond well to an anti-epileptic drug (AED), have a better chance for remaining seizure-free in the future. In general, patients who do not have good control with medications are more likely to have difficulty with epilepsy treatment.

Injuries from Falls. Because many people with seizures fall, injuries are common. Although such injuries are usually minor, people with epilepsy have a higher incidence of fractures than those without the disorder. Epilepsy patients who take the drug phenytoin have an even higher risk, since the drug can cause osteoporosis.

Household Accidents. According to a 2006 study, the kitchen and bathroom are two of the most dangerous places for children with epilepsy. Parents should take precautions to prevent burning accidents from stoves and other heat sources. Children with epilepsy should never be left alone when bathing.

Driving and the Risk for Accidents. Being unable to drive is an extremely distressing and severe component of epilepsy. Drivers with well-controlled epilepsy are not at a high or unacceptable risk for automobile accidents. Uncontrolled epilepsy, however, poses a high risk. Needless to say, seizures can be very dangerous if they occur while a person is driving. Studies have reported that more than a fourth of drivers with uncontrolled epilepsy had a seizure-related accident at some time. Many of these accidents resulted in injuries to the patient or others.

Certain factors can help predict who may safely drive:

A long duration between seizures. In one study, being seizure-free for 6 months reduced the risk for accidents by 85%, and being seizure-free for 1 year lowered the risk by 93%. State laws restricting driving in people with seizures vary from requiring seizure-free periods of 3 months (which is too short for protection) to 18 months.
Having few seizure-related accidents.
Having a reliable pre-seizure warning sign, such as an aura.

Accidents while Swimming. Swimming poses another danger for people with epilepsy, particularly those with tonic seizures, which can cause the diaphragm to expel air quite suddenly. People with epilepsy who swim should avoid deep and cloudy water (a clear swimming pool is best), and always swim with a knowledgeable, competent, and experienced companion or have a supervisor on site.

Epileptic patients who are cured have a normal lifespan. Their long-term survival rates are lower than average if medications or surgery fail to stop the seizures. The lower survival rate is partly due to a higher-than-average risk for death due to accidents and suicide. The specific cause of the seizure may also contribute to fatalities.

There is a very low risk for sudden death in patients with epilepsy. Although the causes of such events are not fully known, experts suspect heart arrhythmias in many cases.

Long-Term General Effects. In general, the long-term effects of seizures vary widely depending on the seizure's cause. The long-term outlook for children with idiopathic epilepsy (epilepsy of unknown causes) is very favorable. One study reported that 68 - 92% of these patients were seizure-free after 20 years. Another study reported that they had a survival rate no different from children without these seizures.

Children whose epilepsy is a result of a specific condition (for example, a head injury or neurologic disorder) have higher mortality rates than the normal population, but their lower survival rates are most often due to the underlying condition, not the epilepsy itself.

Effect on Memory and Learning. The studies on the effects of seizures on memory and learning vary widely and depend on many factors. In general, the earlier a child has seizures and the more extensive the area of the brain affected, the poorer the outcome. Children with seizures that are not well-controlled are at higher risk for intellectual decline.

Social and Behavioral Consequences. Learning and language problems, and emotional and behavioral disorders, occur in a significant number of children with several of the partial epilepsy syndromes. These children perform worse on behavioral tests than do other children. Whether these problems are caused by the seizure disorder and anti-seizure medications or are simply part of the seizure disorder remains unclear.

Effect on Mental Functioning in Adults. The effects of adult epilepsy on mental functioning are not clear. More research is needed in this area, as results have been contradictory.

Psychological Health. About 25 - 75% of adults with epilepsy show signs of depression. People with epilepsy have a high risk for suicide, particularly in the first 6 months following diagnosis. The risk for suicide is highest among people who have epilepsy and an accompanying psychiatric condition such as depression, anxiety disorder, schizophrenia, or chronic alcohol use.

Overall Health. Many patients with epilepsy describe their overall health as "fair" or "poor," compared to those who do not have epilepsy. People with epilepsy also report a higher frequency of pain, depression, anxiety, and sleep problems. In fact, their overall health state is comparable to people with other chronic diseases, including arthritis, heart problems, diabetes, and cancer. Treatments can cause considerable physical effects, such as osteoporosis and weight changes.

Effects on Sexual Function. There have been studies suggesting that up to two-thirds of patients with epilepsy experience sexual disturbances, including impotence in men. Causes of these problems may be emotional, medication induced, or a result of changes in hormone levels:

Epilepsy in childhood may cause disturbances in hormones regulating puberty.
Persistent seizures in adults may be associated with other hormonal and neurologic changes that contribute to sexual dysfunction.
Negative emotions due to epilepsy can reduce sexual drive.
Medications may be responsible for many of these cases, although newer drugs may reduce this problem.

Studies have been conflicting on the effects of fertility from epilepsy, but most suggest that fertility rates among women with epilepsy are lower than among women in the general population. A number of factors, including anti-epileptic drugs (AEDs) or social factors such as marriage at an older age, may contribute to this lower rate. Certain AEDs, particularly valproate, disrupt ovulation and menstruation by increasing male hormone levels and weight and causing polycystic ovaries.

Preparing to Become Pregnant. A woman should visit her doctor at least 3 months before becoming pregnant to talk about risks of medications and the possibility of making any changes.

A woman who has been seizure-free for 2 or more years may attempt to discontinue drugs under her doctor’s supervision.
If she has not been seizure-free, she should continue medications but try to reduce them to a single drug, if possible. (Again, under a doctor’s supervision.)
If a woman taking antiseizure medications has an unplanned pregnancy, there may be no point in switching medications right away, since the effects of the drugs last for 10 weeks. However, she should notify her doctor immediately.
Folic acid is recommended for all pregnant women, and women with epilepsy should talk with their doctor about taking a supplement of folic acid (5 mg) at least 3 months before conception as well as during the first trimester.

Effect of Pregnancy on Seizure Frequency. The frequency and intensity of seizures vary widely in women with epilepsy. About 25% of pregnant women with epilepsy face an increase in events, and the risk is highest in those who have more than one seizure per month prior to becoming pregnant. In most cases, however, there is no change at all. Some pregnant women even have a decrease in seizures. The risk is lower in women who experience less than one seizure in the 9 months prior to becoming pregnant.

The following conditions may contribute to an increase in seizures during pregnancy:

Nausea and vomiting (vitamin B6 and antihistamines may help with nausea)
Fluid retention
Higher estrogen levels
Psychological and emotional stress
Medication noncompliance from fear of side effects
Problems with sleeping
Changes in absorption of anticonvulsants

Anti-epileptic drug levels are monitored at least three times during the pregnancy, more often if seizures are occurring or levels are not normal. Dosage levels should be adjusted accordingly.

Effects of Epilepsy on the Pregnant Patient and the Fetus. Women who become pregnant have a risk for uncontrolled seizures and birth defects from antiseizure medications. In studies of women who were carefully monitored, however, 95% of pregnancies (which is close to normal) had favorable outcomes.

Isolated seizures do not appear to pose any adverse effects to the mother or the unborn child, but repeated seizures and status epilepticus can lead to great dangers. In one study, the effect of epilepsy on complications during pregnancy was the same as in non-epileptic women except for a higher rate of premature deliveries (8.2% in the women with epilepsy).

Drugs Used During Pregnancy. Some types of anti-epileptic drugs (AEDs) can increase the risks for birth defects, especially when taken during the first trimester of pregnancy. Expert guidelines advise that pregnant women use the most effective medication for their type of epilepsy at the lowest dose possible to control seizures. They should also have their doctors take blood tests during pregnancy to monitor their drug levels.

The fetus should be carefully monitored with ultrasonic evaluation and sometimes amniocentesis (visual tests and examination of the fluid in the womb for birth defects and other fetal problems).

In general, research indicates that 90% of women who take AEDs will give birth to healthy children. Still, doctors recommend that women of child-bearing age use a drug other than valproate if possible.

The risk for malformation is higher when more medications are used. For example, there is a 3% risk of birth defects with women who use one anticonvulsant. The risk increases to 20% when four drugs are used.

Birth Defects Associated with Medication. The most common birth defects related to anti-epileptic drugs are:

Cleft lip or palate (risks from lamotrigine, phenobarbital, phenytoin, valproate especially when taken during the first trimester).
Genital or urinary abnormalities (risk from most standard drugs).
Neural tube defects (NTD) in the skull or spinal column (risk of 2% with valproate and 1% with carbamazepine). These complications are most often due to lower folic acid levels caused by both pregnancy itself and antiseizure drugs. Folic acid supplements can help prevent this problem.
Mental impairment (known risk with phenytoin and valproate; inconclusive in carbamazepine and phenobarbital).
Heart defects (risk from phenobarbital, phenytoin, valproate).

Many antiseizure drugs also cause a deficiency in vitamin K clotting factors that increases the risk for hemorrhage in the newborn. Treatment with vitamin K during the last month of pregnancy and a single dose given to the newborn is recommended.

Labor and Delivery. Seizures occur during labor and after delivery in a small percentage of women with epilepsy. The following labor complications are more common among pregnant women with epilepsy: Vaginal bleeding, anemia, and preeclampsia (extremely high blood pressure in the third trimester). If seizures occur during labor, they are generally treated intravenously with benzodiazepines or phenytoin. If tonic-clonic seizures, absence seizures, or status epilepticus occur, a cesarean section may be appropriate.

Postnatal Care

Monitoring the Infant. The infant should be thoroughly examined for any birth defects. Also, if the mother was given phenobarbital or primidone while pregnant, the infant should be monitored for up to 8 months to see if withdrawal symptoms develop. Drug dosages will also need to be adjusted for the mother after delivery.

Breast-feeding. Women on most AEDs typically can nurse their babies, since usually only a small amount of the drug enters the breast milk. The lowest levels are with phenytoin and valproate. (Ethosuximide and possibly levetiracetam are exceptions and should be avoided when a woman is breast-feeding. Women taking phenobarbital are also usually advised not to nurse.) A mother should watch for signs of lethargy or extreme sleepiness in her infant, which could be caused by her medication.

Diagnosis

An epilepsy diagnosis is often made during an emergency visit for a seizure. If a person seeks medical help for a previous or suspected seizure, the doctor will ask about the patient's medical history, including seizure events.

Conditions that cause similar symptoms to epilepsy include:

Syncope. Syncope, a brief lapse of consciousness in which blood flow is reduced to the brain, can mimic epilepsy. It often misdiagnosed as epilepsy. Patients with syncope do not have the rhythmic contracting and then relaxing of the body's muscles.
Migraines. Migraine headaches, particularly migraine with auras, may sometimes be confused with epilepsy. With epileptic seizure, the preceding aura is often seen as multiple, brightly colored, circular spots, while migraine sufferers tend to see black, white, or colorless lined or zigzag flickering patterns. Typically the migraine pain expands gradually over minutes toward one side.
Panic Attacks. In some patients, partial seizures may resemble a panic disorder. Symptoms of panic disorder include palpitations, sweating, trembling, sensation of breathlessness, chest pain, feeling of choking, nausea, faintness, chills or flushes, fear of losing control, and fear of dying.
Narcolepsy. Narcolepsy, a sleep disorder that causes a sudden loss of muscle tone and excessive daytime sleepiness, can be confused with epilepsy.

Electroencephalogram (EEG). The most important diagnostic tool for epilepsy is an EEG, which measures brain waves. Ideally, it should be performed within 24 hours of a seizure. An EEG recording session may last for less than an hour, but in some cases the doctor will want a day-long recording. Long-term monitoring may be necessary in some cases when patients do not respond to medications. Portable EEG units are available in some places, which can be used to monitor patients throughout normal activities. EEGs are not foolproof. Repeated EEGs are often needed to confirm a diagnosis, particularly for certain partial seizures that often produce an initially normal EEG reading.

Video Electroencephalography (Video EEG). For this task, patients are admitted to a special part of the hospital where they are monitored both by EEG and are also watched by a video camera. Patients may need this for a variety of reasons including withdrawal or addition of medications in a patient with difficult-to treat-epilepsy, before epilepsy surgery for some patients, and also when psychogenic nonepileptic seizures are suspected.

Computerized Tomography (CT) Scans. Usually, the first brain imaging test ordered for most adults and children with first-time seizures is a CT scan. This imaging technique is sensitive enough for most purposes. In children, even if the scan is normal, the doctor will follow up to be sure other problems are not present.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of both the bony structures and the soft tissues. Clear images of organs such as the brain, muscles, joint structures, veins and arteries, as well as anomalies like tumors and hemorrhages may be obtained with or without the injection of contrasting dye.

Magnetic Resonance Imaging (MRI). Experts strongly recommend MRIs for children with first seizures in certain cases, such as children under 1 year old and those with seizures that are associated with any unexplained significant mental or motor problems. These images may help to determine if the disorder can be treated with surgery, and may be used as a guide for surgeons.

Other Advanced Imaging Techniques. More advanced scanning techniques are emerging as important tools for epilepsy researchers. By detecting abnormalities, such as changes in brain activity, positron emission tomography (PET) may help locate damaged or scarred locations in the brain where partial seizures are triggered. These findings may help determine which patients with severe epilepsy are good candidates for surgery. Single-photon emission computer tomography (SPECT) may also be used to decide if the surgery should be performed and what part of the brain needs to be removed. Both of these imaging techniques are generally only needed when an MRI of the brain has not been helpful.

Treatment

You cannot stop a seizure, but you can help the patient prevent serious injury.

Remain calm, and do not panic, then take the following actions:

Wipe away any excess saliva to prevent obstruction of the airway. Do not put anything in the patient's mouth. It is an old wives' tale that people having seizures will swallow their tongues.
Turn the victim gently on the side. Do not try to hold the patient down to prevent shaking.
Rest the patient's head on something flat and soft to protect it from banging on the floor and to support the neck.
Move sharp objects out of the way to prevent injury.

Do not leave the seizure victim alone. Anyone nearby should call 911. Patients should be taken to an emergency room when:

A first-time seizure occurs
Any seizure lasts beyond 2 - 3 minutes
The patient has been injured
The patient is pregnant
The patient is diabetic
Parents, caregivers, or bystanders are at all uncertain

Not all patients with chronic epilepsy need to go to the hospital after a seizure. Hospitalization may not be necessary in many patients whose seizure is not severe or repetitive, and who have no risk factors for complications. All patients or caregivers, however, should contact their doctor after a seizure occurs.

Initial Management. The earlier a patient is treated, the better the results. Initial management of status epilepticus consists of:

Administer any seizure medications
Support systems to maintain or attain normal breathing, blood pressure, electrolyte balances, body temperature, and heart functions
Oxygen for patients who may need it
Attention by medical personnel trained to determine any treatable cause of status epilepticus, such as drug withdrawal, low blood sugar, infection, substance abuse (particularly cocaine), or eclampsia (elevated blood pressure induced by pregnancy)

Medications for Status Epilepticus. Doctors will try one or more of the following medications initially:

Benzodiazepine. An intravenously (IV), intramuscularly, or rectally administered benzodiazepine such as lorazepam (Ativan), diazepam (Valium), clonazepam, or midazolam (Versed) is usually used.
Phenytoin or Fosphenytoin. Many doctors use phenytoin or fosphenytoin if seizures are not controlled by a benzodiazepine.
Phenobarbital. Although effective, barbiturates, such as phenobarbital (Barbita, Luminal), are generally used only when other drugs have failed.

All of these medications carry a risk for hypotension, an abrupt and possibly dangerous drop in blood pressure, which may require treatment.

Treatment After The First Seizure

Children with febrile seizures rarely have any long-term effects and generally do not require drug treatment. In very rare cases, children experience severe fever-related seizures known as complex febrile convulsions. In such cases, there is a risk for brain injury that may lead to temporal lobe epilepsy, but this is very small. Such seizures last over 15 minutes, occur more than once within 24 hours, and may affect only one side of the body.

Treatment with anti-epileptic drugs (AEDs) is usually initiated or strongly considered for the following patients:

Children and adults who have had two or three seizures, unless there is either a long separation between seizures or the seizure is provoked by an injury or other specific causes. (In children, risk for recurrence after a single unprovoked seizure is rare. The risk even after a second seizure is low, even when the seizure is prolonged.)
Children and adults after a single seizure if tests reveal any brain injury, or if specific syndromes put a person at special risk for recurrence, for instance, in cases of myoclonic epilepsy.

There is some debate about whether to treat every adult patient with an AED after a single initial seizure. Some experts do not recommend treating adult patients after a single seizure if they have a normal neurologic examination, EEG, and imaging studies. A 2005 study of patients with single or infrequent seizures found that while early AED treatment reduced the risk of seizure for a few years, it had no effect on long-term outcomes. This study also suggested that delaying AED treatment does not increase the risk of developing lifelong epilepsy.

Some doctors believe, however, that any adult who has a first seizure should begin on-going AED treatment, since 30 - 70% of these patients are likely to experience a subsequent event. According to one study, when young adults were given a single drug (usually carbamazepine) after a first generalized seizure, only 22% had a subsequent seizure compared to about 70% of those who were not given treatment.

Most epileptic seizures can be controlled using a single-drug regimen. First-line AED drugs include phenytoin (Dilantin), carbamazepine (Tegretol, Carbatrol), and divalproex sodium (Depakote). Patients generally begin with low doses and build up until the seizures are controlled or a toxic reaction occurs. If a single drug fails to control seizures, other drugs are added on. The specific drugs and whether more than one should be used are determined by various factors, including the patient's age and the seizure's type, frequency, and cause.

Drugs fail to control epilepsy in about 30% of patients. For patients who have little or no benefit from their initial drug regimen the likelihood of good or complete control from different medications or multidrug regimens is not very high.

Reasons for Failure. An AED may fail to reduce seizures due to such factors as:

The wrong dose level.
Improper timing.
Introducing the medication too rapidly.
Not managing conditions that triggered the seizure.
Instability of the drugs. Many of the tablet forms disintegrate easily with moisture, so pills should be stored in a dry place, not in the bathroom, and kept away from heat.
Patients not taking medication as prescribed. Over 40% of patients experience toxic or bothersome effects from older AEDs, which often causes them to withdraw. Among the most distressing are sleepiness, problems in coordination, and weight gain.
Some evidence suggests that about a quarter of patients who do not respond to AEDs actually have nonepileptic seizures that in many cases are caused by psychiatric conditions (such as panic attack or personality disorders).

The doctor should first address these issues. If the patient still does not respond, the doctor will usually try a different drug. If this fails, one or even two additional drugs at a time may be used. When seizures do not respond to the first two or three drugs, the odds of a fourth or fifth working diminish greatly, despite a number of new medications on the market. In such cases, the patient should ask about surgical alternatives.

Healthy Behaviors. In young people, a positive attitude, continued support from family and health care providers, emotional well-being, and good treatment results can increase patient compliance. Unhealthful behaviors, such as smoking and alcohol use, can have a negative effect.

During the first few months of therapy, the doctor will probably order blood tests once or twice to monitor drug levels and, if necessary, adjust dosages. Monitoring is used to check for AED complications, and to be sure the patient is complying with the regimen. Many experts feel, however, that these blood tests are a less reliable indicator of problems than the patient's own self-observations of his or her responses to the drug. For instance, blood tests may suggest that the dosage levels are insufficient according to general standards, yet the individual patient may be seizure-free and leading a normal life. It is very important that women have AED levels monitored during pregnancy.

An estimated 60% of all patients treated effectively can stop taking AEDs within 5 - 10 years. Evidence suggests that medications in children should not be halted for at least 2 years after the last seizure, particularly if they have partial seizures and abnormal EEGs. It is not clear whether children who have been free of generalized seizures need to wait more than 2 years or if they can withdraw earlier.

Children who tend to relapse after withdrawal from treatment usually have the following conditions or situations:

A family history of epilepsy
Require multiple medications to control seizures
Abnormal EEG readings after treatment has started
Partial seizures

There is also no clear evidence on whether adults who are free of any seizure type can safely withdraw from their medications within 2 years of their last seizure of if they should wait.

In any case, attempts to halt drugs should be done during periods when seizures will cause the least harm. For instance, the best time to test the effects of drug withdrawal in teenagers might be about a year before they are eligible to drive.

Anti-epileptic drugs interact with many other drugs, and may cause special problems in older patients who use multiple medications for other health problems. Elderly patients should have liver and kidney function tests performed before starting antiseizure medication. Standard drugs are usually effective, while safe, newer ones (including gabapentin, lamotrigine, oxcarbazepine, and gamma-vinyl-GABA) may sometimes prove to be useful as a sole therapy. These newer drugs also increase patient compliance because they tend to have fewer side effects than the older ones.

Hormonal fluctuations affect epilepsy in about a third to a half of female patients. Estrogen appears to increase activity, and progesterone reduces it. The effect of pregnancy on women with epilepsy is complex. The following treatments may help or affect women with epilepsy:

Hormonal Drugs that Suppress Ovulation. When seizures in women are worsened by hormonal changes, such as during the menstrual cycle, suppressing ovulation may be recommended using drugs called gonadotropin-releasing hormone agonists.
Oral contraceptives. Antiseizure medications affect many oral contraceptives (OCs). Carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and topiramate reduce the effects of OCs. Valproate does not, and may even increase hormonal levels. Gabapentin, lamotrigine, tiagabine, and vigabatrin may also prove to be safe with OCs, but more research is needed. Progestins may be the best contraceptive drugs for women with epilepsy at this time. Injected progestins may actually help prevent seizures in some cases.

More information on epilepsy and pregnancy can be found in this report under Outlook and Effects.

Medications

Many newer anti-epilepsy drugs (AEDs) are now available and are usually better tolerated than the older, standard AEDs. They often cause less sedation and require less monitoring. Although they are generally approved for use as add-ons to standard drugs that fail to control seizures, many doctors are now prescribing them as single drugs. Specific choices usually depend on the individual's particular condition and the specific side effects of the AED. None has emerged as being superior to either standard or newer drugs. All appear to offer some benefits, but, as with standard antiseizure drugs, they also have troublesome side effects.

Valproate (Depakene, valproic acid) and its delayed release form, divalproex sodium (Depakote), are anticonvulsants. Valproate is the most widely prescribed anti-epileptic drug worldwide.

Uses. Valproate is the first choice for patients with generalized seizures and is used to prevent nearly all other major seizures as well.

General Side Effects. These drugs have a number of side effects that vary depending on dosage and duration. Most side effects occur early in therapy and then subside. General side effects include:

Stomach and intestinal problems, which are experienced by nearly half of patients after starting the drugs and may still occur after several years of use. Divalproex sodium (Depakote) has a lower risk for these side effects than valproate (Depakene).
Increased appetite with significant weight gain often becomes a problem and can be a major reason for noncompliance, particularly in young people.
Hand tremors, irritability, and hyperactivity in children are fairly common.
Temporary hair thinning and hair loss have occurred. Taking zinc and selenium supplements may help reduce the effect.
Young girls may develop secondary male characteristics, and premenopausal women are at increased risk for menstrual irregularities and polycystic ovaries, due to elevated male hormones. The effects are reversible. (These side effects also appear in women using other anti-epileptic drugs, but the risk from valproate appears to be higher.)
Studies have reported symptoms of Parkinson's disease preceded by hearing loss in people who have taken it for more than a year, but they were reversible when the drug was withdrawn.
Valproate poses a higher risk for serious birth defects than many other AEDs. These birth defects include skull and limb deformities, and brain, heart, and lung problems. Experts recommend that women of child-bearing age use a different type of anti-epilepsy drug than valproate. If valproate is used, it should be prescribed at the lowest possible dose.
Cases of pancreatitis, a serious and even life-threatening inflammation in the pancreas, have been reported in children and adults taking valproate. (It is still very rare, however.)
Valproate and divalproex sodium are not usually recommended for young children because of an unusual, but potentially fatal, toxic effect on the liver. This very rare effect is most likely to affect children under 2 years of age who have birth defects and are taking more than one antiseizure drug. Some doctors recommend monitoring blood levels for liver function once prior to administering valproate or divalproex sodium, monthly during the first 6 months, and then periodically after that.
Children with epilepsy who take valproic acid may eventually develop some problems in the kidney, although they are generally not significant.

Symptoms of Toxic Side Effects in Liver or Pancreas.

Abdominal pain
Nausea or vomiting
Loss of appetite
Lethargy
Acute confusion
Water retention
Easy bruising
Yellowish skin coloring

Carbamazepine (Tegretol, Equetro, Carbatrol) is an effective anticonvulsant and specific analgesic when used alone or with other drugs. Carbamazepine also has the added benefit of relieving depression and improving alertness. An extended release form is available that allows twice-daily dosing rather than 3 times a day. A chewable form makes it easier for children to take.

Uses. This drug is used to prevent the following seizures or epilepsy syndromes:

Partial seizures. Patients tend to tolerate this drug better than others, although responses differ among individuals
Grand mal seizures
Combinations of grand mal and partial seizures
Autosomal dominant nocturnal frontal lobe epilepsy (an inherited disorder).

Side Effects. Different side effects may develop or resolve at different points in the treatment duration. Initial side effects may include:

Double vision, headache, sleepiness, dizziness, and stomach upset. These usually subside after a week and can be greatly reduced by starting with a small dose and building up gradually.
Some people experience visual disturbances, ringing in the ears, agitation, or odd movements when drug levels are at their peak. The extended-release form of carbamazepine (Carbatrol) may help reduce these symptoms.

Serious side effects are less common but can include:

Carbamazepine may increase the risk for birth defects, especially if it is taken during the first trimester of pregnancy.
Skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, so severe the drug has to be discontinued develop in about 6% of patients. These skin reactions cause skin lesions, blisters, fever, itching, and other symptoms. People of Asian ancestry have a 10 times greater risk for skin reactions than other ethnicities. The FDA recommends that patients of Asian ancestry get a blood test prior to starting the drug to determine if they have the gene variant that increases this risk.
Water retention can be a problem in older people.
Hormonal changes, particularly higher levels of male hormones in both men and women, pose some risk for sexual dysfunction over time.
A decrease in white blood cells occurs in about 10% of those taking the drug. This is generally not serious unless infection accompanies it.
Other blood conditions can arise that are also potentially serious. Patients should be sure to inform the doctor if they have any sign of irregular heartbeats, sore throat, fever, easy bruising, or unusual bleeding.
Long-term therapy can cause bone loss (osteoporosis) in women, who should take preventive calcium and vitamin D supplements.
Children are at higher risk for behavioral problems.

Note: Citrus fruit, especially grapefruit, can increase carbamazepine's adverse effects and should be avoided by those taking this drug.

Uses. Phenytoin (Dilantin) is effective for adults who have the following seizures or conditions:

Grand mal seizures
Partial seizures
Status epilepticus
Can be effective for people with head injuries who are at high risk for seizures

This drug is not useful for the following seizures:

Petit mal seizures
Myoclonic seizures
Atonic seizures

Side Effects. Side effects are sometimes difficult to control. Some people may develop a toxic response to normal doses, while others, such as those with alcoholism, may require higher doses to achieve benefits. As with any drug, side effects generally rely on dosage and duration. Using phenytoin in combination with newer add-on drugs can allow lower doses and may reduce some of the risks. Side effects may include:

Excess body hair, eruptions and coarsening of the skin, and weight loss
Gum disease
Staggering, lethargy, nausea, depression, eye-muscle problems, anemia, and an increase in seizures can occur as a result of high doses.
Liver damage may develop in rare cases.
Bone loss from long-term therapy. Patients should take preventive calcium and vitamin D supplements and exercise regularly to improve bone mass.
Severe and even rare life-threatening skin reactions (Stevens-Johnson syndrome)
An increased risk for birth defects

Phenobarbital (Luminal), also called phenobaritone, is a barbiturate anticonvulsant and is often the initial drug prescribed for newborns and young children. It is a relatively inexpensive drug. Primidone (Mysoline) is converted in the body to phenobarbital, and has the same benefits and adverse effects. It is reported that primidone is not as well-tolerated as phenobarbital. Some experts believe that primidone has no advantage over the other drug.

Uses. Barbiturates are used to also prevent grand mal (tonic-clonic) seizures or partial seizures. They are no longer typically used as a first-line drug.

Side Effects. Phenobarbital has fewer toxic effects on other parts of the body than most anti-epileptic drugs, and drug dependence is unusual, given the low doses used for patients with epilepsy. Nevertheless, withdrawal is common because of side effects, and therefore it is less likely to be used over time than other drugs, including phenytoin, another relatively inexpensive but effective drug.

Patients sometimes describe their state as "zombie-like." The most common and troublesome side effects are:

Drowsiness
Memory problems
Problems with tasks requiring sustained performance
Problems with motor skills
Hyperactivity in some patients, particularly in children and the elderly
Depression in some adults

Some controversy has arisen over studies indicating that children taking phenobarbital score lower on intelligence tests, even for some months after going off the drug.

Uses. Ethosuximide (Zarontin) is used for petit mal (absence) in children and adults when the patient has experienced no other type of seizures. Ethosuximide succeeds in abolishing petit mal seizures in 60% of patients and controls them in up to 90%. Methsuximide (Celontin), a drug similar to ethosuximide, may be suitable as an add-on treatment for intractable epilepsy in children without causing serious or permanent side effects.

Side Effects. Use of this drug can cause stomach problems, dizziness, loss of coordination, and lethargy. In rare cases, it has caused severe and even fatal blood abnormalities. Periodic blood counts are recommended for patients taking this drug.

Uses. Clonazepam (Klonopin) is recommended for myoclonic and atonic seizures that cannot be controlled by other drugs and for Lennox-Gastaut (absence variant). It may be useful in newborns when other drugs are ineffective. Although clonazepam can prevent generalized or partial seizures, patients generally develop tolerance to the drug, and then seizures recur.

Side Effects. People who have had liver disease or acute angle glaucoma should not take clonazepam, and people with lung problems should approach the drug with caution. Clonazepam can be addictive, and abrupt withdrawal has been known to trigger status epilepticus. Side effects include the following: drowsiness, imbalance and staggering, irritability, aggression, hyperactivity in children, weight gain, eye muscle problems, slurred speech, tremors, skin problems, and stomach problems.

Uses. Lamotrigine (Lamictal) is approved as add-on (adjunctive) therapy for partial seizures, and generalized seizures associated with Lennox-Gastaut syndrome, in children aged 2 years and older and in adults. Lamotrigine is also approved as add-on therapy for treatment of primary generalized tonic-clonic (PGTC) seizures, also known as “grand mal” seizures, in children aged 2 years and older and adults. Lamotrigine can be used as a single drug treatment (monotherapy) for adults with partial seizures who have not responded to monotherapy with carbamazepine, phenytoin, phenobarbital, primidone, or valproate. Birth control pills lower blood levels of lamotrigine.

Side Effects. Common side effects include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, and rash. Although most cases of rash are mild, in rare cases the rash can become very severe. The risk of rash increases if the drug is started at too high a dose or if the patient is also taking valproate. (Serious rash is more common in young children who take the drug than it is in adults.) Rash is most likely to develop within the first 8 weeks of treatment. Be sure to immediately notify your doctor if you develop a rash, even if it is mild.

Studies suggest that lamotrigine may cause fewer problems with sexual function in men than other antiseizure drugs. A 2006 study indicated that lamotrigine may cause fewer cognitive problems (such as confusion and difficulty concentrating) than topiramate.

Gabapentin (Neurontin) is an effective add-on drug for controlling complex partial seizures and secondarily generalized partial seizures and is approved for adults and children with these seizures. It has achieved response rates in patients with resistant partial epilepsy. It is not at all useful for generalized petit mal seizures.

Side Effects. Its toxicity is low, and side effects include sleepiness, headache, fatigue, and dizziness. Some weight gain has been reported. Gabapentin has no significant interactive effects when taken with other drugs. Children may experience hyperactivity or aggressive behavior. Long-term adverse effects are still unknown.

Pregabalin (Lyrica) is similar to gabapentin.

Uses. Approved as add-on therapy to treat partial-onset seizures in adults with epilepsy. In clinical trials, half of the patients who received pregabalin experienced a 50% reduction in seizure frequency.

Side Effects. These may include dizziness, sleepiness, dry mouth, swelling in hands and feet, blurred vision, weight gain, and trouble concentrating

Uses. Topiramate (Topamax, generic) is similar to phenytoin and carbamazepine and is effective and safe for a wide variety of seizures in adults and children. It is approved as add-on therapy for patients 2 years and older with generalized tonic-clonic seizures, partial-onset seizures, or seizures associated with Lennox-Gastaut syndrome. It is also approved as single therapy for patients 10 years and older with tonic-clonic seizures or partial-onset seizures. Studies have shown a 34 - 87% reduction in seizure frequency with some patients becoming seizure-free.

Side Effects. Most side effects are mild to moderate and can be reduced or even prevented by beginning at low doses and increasing dosage gradually. Serious side effects may include glaucoma, decreased sweating, increased body temperature, kidney stones, sleepiness, dizziness, confusion, and trouble concentrating. Patients should immediately tell their doctor if they have blurred vision or eye pain. Topiramate may have fewer interactions with oral contraceptives than other AEDs.

Oxcarbazepine (Trileptal, generic) is similar to phenytoin and carbamazepine but generally has fewer side effects.

Uses. Approved as single therapy or add-on therapy for partial seizures in adults and for children ages 4 years and older.

Side Effects. Serious side effects, while rare, include Stevens-Johnson syndrome and toxic epidermal necrolysis. These skin reactions cause a severe rash that can be life threatening. Rash and fever may also be a sign of multi-organ hypersensitivity, another serious side effect associated with this drug. Oxcarbazepine can also reduce sodium levels (hyponatremia). Your doctor may want to monitor the sodium level in your blood. This drug can also reduce the effectiveness of birth control pills. Women who take oxcarbazepine may need to use a different type of contraceptive.

Zonisamide (Zonegran) is a unique drug that blocks sodium and calcium channels and may have nerve-protecting properties.

Uses. It is approved as add-on therapy for adults with partial seizures, and studies indicate it is often effective against infantile spasms (West syndrome) and myoclonic seizures.

Side Effects. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Children are especially at risk for this side effect, which can be serious. (The drug has not been approved for children.) Other side effects tend to decrease over time and include dizziness, forgetfulness, headache, weight loss, and nausea.

Levetiracetam (Keppra) is known as a nootropic drug.

Uses. This drug is approved both in oral and intravenous forms as add-on therapy for:

Partial onset seizures in adults and children ages 4 years and older
Myoclonic seizures in adults and adolescents ages 12 years and older who have juvenile myoclonic epilepsy
Primary generalized tonic-clonic seizures in adults and children ages 6 years and older who have idiopathic generalized epilepsy

Some experts believe that levetiracetam represents a significant advance and will prove to be an important first-line drug. Levetiracetam appears to have fewer drug interactions than other anti-epileptic drugs and may be particularly useful for older patients.

Side Effects. These tend to occur mostly in the first month. They include sleepiness and fatigue, muscle weakness and coordination difficulties, headache, flu symptoms, dizziness, behavioral abnormalities, possible risk of a reduced white blood cell count, and a higher rate of infections. Caution is advised for patients with kidney dysfunction. There have been some reports of adverse effects on mood (irritability, depression, and anxiety), but recent studies have found fewer such effects than with other AEDs. Epilepsy, rather than the drug, is likely to be the cause of these mood changes. About 1% of patients report considerable weight loss.

Tiagabine (Gabitril) has properties similar to phenytoin and carbamazepine, and is also showing promise.

Side Effects. Evidence has reported some significant side effects with its use, including dizziness, fatigue, agitation, and tremor. At least one study suggested that it has more adverse effects than lamotrigine and is not as well tolerated. In February 2005, the FDA issued a warning advising that tiagabine may cause seizures in patients without epilepsy. Tiagabine is only approved for use with other anti-epilepsy medicines to treat partial seizures in adults and children 12 years and older.

Felbamate. Felbamate (Felbatol) is an effective antiseizure drug. However, after reports of deaths from a serious blood condition known as aplastic anemia or from liver failure, felbamate is recommended only under certain circumstances. They include severe epilepsy, such as Lennox-Gastaut syndrome or as monotherapy for partial seizures in adults when other drugs fail.

Vigabatrin. Vigabatrin (Sabril) is a chemical called gamma-vinyl GABA. It was designed to increase the brain levels of gamma aminobutyric acid (GABA), the enzyme that inhibits seizure activity. It has serious side effects, however, and is generally prescribed in the U.S. only in certain cases, such as in low doses for patients with Lennox-Gastaut syndrome. Overseas it is also used for partial seizures and as first-line therapy in children with infantile spasms (West syndrome). Between 10 - 30% of people on long-term treatment have developed irreversible visual disturbances, including reductions in acuity and color vision. Men are at higher risk for this side effect than are women. Further studies are needed to determine the extent and severity of this complication, particularly in children. There is a slight risk for depression or psychosis when vigabatrin is used as add-on therapy, and particularly if the drug is administered too quickly. These risks are far lower if the drug is used as sole therapy.

Older Drugs. Some older but less effective drugs may still play a role against epilepsy:

Acetazolamide (Diamox) is sometimes used against common types of seizures, but patients quickly develop a tolerance for it. Some experts suggest it still may be useful when drug interactions are a problem, when a rapid effect is required, or when an additional drug is needed for a short time.
Trimethadione (Tridione) is effective for petit mal seizures, but has very serious side effects, and its use is severely limited.

Infantile spasms are treated with vigabatrin, adrenocorticotropic hormone (ACTH), or valproate. Some experts recommend that vigabatrin be given first and ACTH administered 10 - 14 days later. In one small study, no infants who were given this combination relapsed after 4 months. Newer drugs may also be effective for this problem, but their effects on small children are not yet wholly known.

New AEDs. Retigabine is an investigational GABA enhancer that works in a different way from existing AEDs. It is currently in phase III trials for treatment of partial-onset seizures in patients who are receiving other AEDs. Talampanel is another new type of drug, known as an AMAP receptor antagonist, that is currently in early trials. Other drugs under investigation are related to existing AEDs. For example, brivaracetam and seletracetam are similar to levetiraceptam, fluorofelbamate is similar to felbamate, and eslicarbazepine is similar to oxcarbazepine.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis) that may have properties that protect nerve cells. Some patients claim a reduction in seizures while other active users of marijuana report no effect on seizures. No one has reported worse seizures from the drug. Animal studies further support some protection from cannabinoids against seizures. Clinical studies using humans have not been conducted.

Melatonin. Melatonin is a hormone found in the brain that is best known for its role in sleep. Some researchers believe that it might have properties that could benefit patients with epilepsy. Melatonin is a powerful hormone that can have major effects on all parts of the body. No one with epilepsy should experiment with this supplement except as part of a clinical trial. In some studies, melatonin has been found to cause seizures in children who have existing neurologic problems.

Surgery

Surgical techniques to remove injured brain tissue may be appropriate for many patients with epilepsy. The surgeon's goal is to remove only the damaged tissue in order to prevent seizures and to avoid healthy brain tissue. Surgical techniques for reaching these goals have improved significantly over the past decades due to advances in imaging and monitoring, new surgical techniques, and a better understanding of the brain and epilepsy.

A number of tests using imaging and electroencephalography (EEG) can determine if surgery is an option:

The general approach is to first use long-term EEG monitoring to locate the brain tissue that triggers the epileptic event.
Advanced imaging techniques can provide valuable additional information. They include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), or single-photon emission computer tomography (SPECT) scans.

If the imaging tests indicate that more than one site is involved or their results conflict, then more invasive monitoring of the brain may be required, although the newer imaging tests are proving to be very accurate tools. If such tests pinpoint a specific area in the brain as the location for seizures, surgery is possible. MEG, for example, is now approved for imaging parts of the brain involved with motor control, sensation, and language function, and may become important in evaluating patients who are likely candidates for surgery. The doctor will also examine the test results to determine if the offending nerve cells perform vital functions and try to predict surgical outcome in certain cases.

The major areas of the brain have one or more specific functions.

The most common surgical procedure for epilepsy is temporal lobectomy, which is performed when epilepsy occurs in the temporal lobe. (Surgery is not as successful in epilepsies that occur in the frontal lobe.) It involves removing small portions from the hippocampus. The hippocampus is a part of the brain that is involved in memory processing. It is part of the limbic system, which controls emotions.

Click the icon to see an image of the limbic system of the brain.

Candidates. Candidates for this surgery usually have a history of seizures. Anti-epileptic drugs have not helped them. Young children may be more difficult candidates because they often have injured areas outside the temporal lobes. Nevertheless, surgery can be very successful in many children, even if more than one area is involved.

Success Rates. New imaging techniques are dramatically improving the success rates of temporal lobe surgery. Studies have shown that many patients remain seizure-free after temporal lobectomy. In a randomized controlled trial, around 60% of patients became free of disabling seizures after surgery versus only 8% of patients treated with medications. In general, around 60 - 80% of patients are seizure free 1 - 2 years after surgery.

Patients may still need to take medications after surgery, even if seizures are very infrequent. Cure is not always possible, and some patients may still experience some seizures. Double vision is very common after the operation, but it is typically temporary and resolves within a few months.

Studies also suggest that temporal lobe surgery improves quality of life and can help relieve depression and anxiety. Other studies indicate that surgery may even prolong survival. Some experts theorize that surgery stabilizes parts of the brain that influence heart rate and may reduce the risk of sudden death, a rare complication of epilepsy.

Effects on Mental Functioning. Although surgery on the left temporal lobe does not impair intelligence to any significant degree, some studies suggest negative effects of mental functioning and behavior. A risk of impairment of verbal memory is also present.

In general, surgical effects on mental functioning and behavior depend on the extent and location of the surgical area.

Lesionectomy is a procedure that removes abnormal tissues in certain conditions, such as:

Cavernous angiomas (abnormal clusters of blood vessels)
Low-grade brain tumors
Cortical dysplasias (these are abnormalities in fetal development in which the normal migration of nerve cells is altered for some reason)

This local surgery, which can cure the patient's epilepsy, has become possible with the advent of advanced imaging techniques such as MRI.

Other surgical procedures called hemispherectomy and corpus callosotomy offer hope for specific patients. They include infants and young children with catastrophic seizures that occur in one, or part of, a hemisphere and for patients whose seizures are due to specific structural brain abnormalities or tumors.

Hemispherectomy. Hemispherectomy is the removal of half the brain, leaving the deep structures intact. Surgery can take 12 hours and there is always some paralysis on one side of the body. There is also a small risk for hydrocephalus, coma, or even death. Quality of life is almost always improved, however, and the surgery does not reduce intelligence.

Corpus Callosotomy. Corpus callosotomy involves cutting the nerve fibers that connect one side of the brain to another. It does not remove brain tissue. It may be done in two stages. In the first, there is a partial separation. If seizures continue, the surgeon may perform a complete separation. This surgery can reduce (although not entirely stop) uncontrolled tonic clonic seizures. It has been used in patients with specific syndromes, such as Lennox-Gastaut syndrome. The procedure can have very severe complications, however.

Electrical stimulation of areas in the brain that affect epilepsy is helping many patients with refractory epilepsy. Vagus nerve stimulation (VNS), an electrical stimulation of the vagus nerve, is now an accepted therapy for severe epilepsy that does not respond to AEDs. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. They affect swallowing, speech, and many other functions. They also appear to connect to parts of the brain that are involved with seizures. The procedure is as follows:

Click the icon to see a depiction of epilepsy treatment.

A battery-powered device similar to a pacemaker is implanted under the skin in the upper left of the chest.
A lead is then attached to the left vagus nerve in the lower part of the neck.
The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. (Patients may also pass a magnet over the device to give it an extra dose if they sense a seizure coming on. This appears to help about 25 - 30% of patients.)
The batteries wear out after 3 - 5 years and need to be removed and replaced by a simple surgical procedure.

An investigational approach called deep brain stimulation (DBS) targets the thalamus, the part of the brain that produces most epileptic seizures. Early results have been promising. Researchers are also studying other implanted brain and nerve stimulation devices such as the responsive neurostimulator system (RNS), which detects seizures and stops them by sending electrical stimulation to the brain. A third investigational approach, trigeminal nerve stimulation (TNS), stimulates a nerve involved in inhibiting seizures.

Candidates. The American Academy of Neurology recommends VNS for:

Patients who are over 12 years old, and
Have partial seizures that do not respond to medication, and
Are not appropriate candidates for surgery

Evidence is accumulating, however, to indicate that VNS is effective and safe for many patients of all ages and for refractory epilepsy of many types.

Success Rates. Studies are reporting that the procedure reduces seizures within 4 months by up to 50% and even more in many patients. Studies report that it has been effective for longer than 7 years. In one study that followed patients for a year, the benefits of VNS appeared to increase over time.

Complications. Vagus nerve stimulation does not eliminate seizures in most patients and is still somewhat invasive. VNS can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Some studies suggest that the treatment causes adverse changes in breathing during sleep and may cause lung function deterioration in people with existing lung disease. People who have obstructive sleep apnea also should be cautious about this procedure. Turning off the VNS (for example before an MRI or surgery) may increase the risk for status epilepticus. (However, VNS may also be helpful for treating status epilepticus in some patients.)

Stereotactic Radio Surgery. Focused beams of radiation are able to destroy lesions deep in the brain without the need for open surgery. Typically used for brain tumors, stereotactic radio surgery is also under investigation for temporal lobe epilepsy and for seizures due to cavernous malformations. It may be used for patients when an open surgical approach is not possible.

Lifestyle Changes

The best preventive measure is to comply strictly with the drug regimen as prescribed. Seizures cannot be prevented by lifestyle changes alone, but people can make behavioral changes that improve their lives and give them a sense of control.

In most cases, there is no known cause for epileptic seizures, but specific events or conditions may trigger them and should be avoided.

Inadequate or Fragmented Sleep. Inadequate or fragmented sleep can set off seizures in many people. In one study, the lowest risk for seizures was during REM sleep (when dreams occur). The highest risk was during light non-REM stages of sleep. Using sleep hygiene or other methods to improve sleep may be helpful.

Food Allergies. Food allergies may provoke seizures in children who also have migraine headaches, hyperactive behavior, and abdominal pains. Parents should consult an allergist if they suspect foods or additives might be playing a role in such cases.

Alcohol and Smoking. Alcohol and smoking should be avoided, although light alcohol consumption does not appear to increase seizure activity in people who are not alcoholics or sensitive to alcohol.

Flashing Lights. Patients should avoid exposure to flashing or strobe lights. Video games have been known to trigger seizures in people with existing epilepsy, but apparently only if they are already sensitive to flashing lights. Seizures have been reported in Japan among people who watched cartoons with rapidly fluctuating colors and quick flashes. The frequency of flashes per second is measured in hertz (Hz). Screens that emit a lower hertz (such as 50 Hz screens sold in Europe) are more likely to cause seizures in people with epilepsy than a higher-hertz screen (such as 100 Hz screens sold in the U.S.).

Relaxation methods include diaphragmatic rhythmic breathing, biofeedback, and meditation techniques. No strong evidence supports their value on reducing actual attacks (although some people have reported that they have), but they may be helpful in reducing anxiety in people who have positive experiences with them. There have been some reports that deep breathing (a common relaxation technique) triggers seizures in certain people.

Exercise is important for many aspects of epilepsy, although it can be problematic. Weight-bearing exercise helps maintain bone density, which can be reduced by many of the medications, particularly the older ones. Exercise can also help to prevent weight gain, which is a problem with some drugs. There have been some reports that exercise may trigger seizures in some patients, but this is uncommon. A number of studies have found no significant association between physical activity and a higher incidence of seizures in patients with epilepsy. Nevertheless, if patients are concerned they should discuss this issue with their doctors.

Some small studies have reported significant benefits from the practice of yoga, which employs weight bearing and balancing postures. In one study, a system of meditation called Sahaja yoga changed EEG readings of brain waves and reduced seizures. Other studies report a 50% reduction in seizures and an overall decline in the number of attacks per month. Still, well-controlled studies are needed to confirm these benefits.

All patients should maintain a healthy diet, including plenty of whole grains, fresh vegetables, and fruits. In addition, dairy foods may be important to maintain calcium levels. Fasting has been used to prevent seizures since ancient times. In the 1920s, a high-fat, no-sugar, low protein diet, known as a ketogenic diet, was used to prevent seizures. It lost popularity after the introduction of anti-epileptic drugs but is now proving to be effective with many children. Researchers are investigating whether the Atkins diet (high protein, low carbohydrate) may help people with epilepsy. Both the ketogenic diet and the Atkins diet can interfere with some anti-epileptic medications such as topiramate. Talk to your doctor before beginning any special diet or a weight loss program.

The ketogenic diet, which is very high in fat (90%), very low in carbohydrates, and low in protein, has been studied and debated for decades. It has proven to be helpful for many children with severe epilepsy that does not respond to AEDs. It is not clear why it works. The standard theory is that burning fat instead of carbohydrates causes an increase in ketones. Excess ketones (called ketosis) appears to alter certain amino acids in the brain and to increase levels of the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.

Benefits of the Ketogenic Diet. Studies report that about 10 - 15% of children who use the diet are seizure free after 1 year, while 30% are nearly seizure free. Some parents report that the diet helps improve their children’s alertness, even if seizures continue. Many children who try the ketogenic diet are able to stop or at least reduce their medications.

Candidates of the Ketogenic Diet. The Ketogenic Diet seems to be most helpful for children who have difficult-to-control seizures, in particular:

Generalized and partial seizures (the diet does not appear to be as helpful for children with partial-onset seizures)
Myoclonic-atastic epilepsy
Infantile spasm

Typical Ketogenic Diet. (This diet must be professionally monitored! Parents can endanger their children if they try the program on their own without consulting a doctor or trained health expert.) The child fasts for the first 1 - 2 days, then the diet is gradually introduced. The regimen uses small amounts of carbohydrates and large amounts of fats (up to 90%), with very few proteins and no sugar. Children generally consume 75% of their usual daily calorie requirements.

A typical dinner may include a chicken cutlet or piece of fish, broccoli with cheese, lettuce with mayonnaise, and a whipped cream sundae. Vegetables may include celery, cucumbers, or asparagus, cauliflower, and spinach. Breakfast might consist of an omelet, bacon, and cocoa with cream. (Artificial sweeteners are used for any desserts.)

The diet is difficult, as a slight deviation from the diet can provoke a seizure. Children cannot take medications that contain sugar (which is common in many drugs produced for children). Some sunscreens and lotions contain sorbitol, a carbohydrate that can be absorbed through skin. About 40 - 50% of patients find the diet too difficult or ineffective and stop it after 6 months.

Researchers are also investigating the Atkins diet, a popular weight-loss diet that has similar effects but is less restrictive than the ketogenic diet. Early results indicate that it might be helpful for some young people. Another alternative is a low glycemic index diet, which contains even fewer carbohydrates than the Atkins diet. Still, parents should not put their children on these diets without support from a doctor.

Side Effects and Complications. To prevent serious side effects, children need regular monitoring by a doctor, especially when the diet is first initiated.

Side effects or complications that may occur at the start of the diet include:

Acidosis, a build-up of acid in the blood and body
Low blood sugar (hypoglycemia)
Stomach upset
Dehydration
Lethargy

Side effects that may occur later on include:

Unhealthy cholesterol and lipid levels
Kidney stones, which may be a complication of acidosis, occur in about 5% of children on the diet. Patients should drink plenty of fluids. Oral potassium citrate (Polycitra K) may be protective.
Slowing of growth (tends to occur more in younger children than older children
Decreased bone density

Because most patients remain on the diet for only 2 years, the risks for potential long-term damage appear minimal.

Many patients with epilepsy and parents whose children have epilepsy can benefit from support associations. These services are usually free and available in most cities.

Tips for Helping Children. Some of the following tips may help the child with epilepsy:

Children should be treated as normally as possible by parents and siblings.
Children should be assured that they will not die from epilepsy.
Often children can be given the hope that they will outgrow the disorder.
Most children will not have seizures triggered by sports or by any other ordinary activities that are enjoyable and healthy.
As soon as they are old enough, children should be active participants in maintaining their drug regimens, which should be presented in as positive a light as possible.

Therapies for Children and Adults. Because of the risks for serious emotional consequences, psychological therapy may be beneficial and even necessary for some adults and children. In one study, cognitive behavioral therapy was helpful in lowering seizure rates in young people with juvenile myoclonic epilepsy. This approach offers a structured counseling program that helps people change behaviors that can reduce seizure risk factors such as anxiety and insomnia.

Resources

www.epilepsyfoundation.org -- Epilepsy Foundation
www.aesnet.org -- American Epilepsy Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke

References

Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol. 2007 Aug;6(:693-8.

Foldvary-Schaefer N, Wyllie E. Epilepsy. In: Goetz C, ed. Textbook of Clinical Neurology. 3rd edition. Saunders. 2007.

Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007 Mar;119(3):535-43.

Johnson MV. Seizures in childhood. In: Behrman RE, ed. Nelson Textbook of Pediatrics. 17th edition. Saunders. 2004.

Krebs PP. Psychogenic nonepileptic seizures. Am J Electroneurodiagnostic Technol. 2007 Mar;47(1):20-8.

Krumholz A, Wiebe S, Gronseth G, et al. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2007 Nov 20;69(21):1996-2007.

Kwan P, Brodie MJ. Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.

Leone MA, Solari A, Beghi E; FIRST Group. Treatment of the first tonic-clonic seizure does not affect long-term remission of epilepsy. Neurology. 2006 Dec 26;67(12):2227-9.

Salanova V, Worth R. Neurostimulators in epilepsy. Curr Neurol Neurosci Rep. 2007 Jul;7(4):315-9.

Spencer SS. Seizures and epilepsy. In: Goldman L, ed. Cecil Medicine. 23rd edition. Saunders. 2007.

Tomson T, Hiilesmaa V. Epilepsy in pregnancy. BMJ. 2007 Oct 13;335(7623):769-73.

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

A.D.A.M. Copyright

adam.com

Herpes simplex virus

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

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Herpes simplex virus (HSV) infections are very common worldwide. HSV-1 (usually known as a cold sore) is transmitted through kissing or sharing drinking utensils, and HSV-2 (usually known as genital herpes) through sexual contact. You may be infected and not show symptoms for a long time. Often symptoms are triggered by exposure to the sun, fever, menstruation, emotional stress, a weakened immune system, or an illness.

There is not cure for herpes, and once you have it, it is likely to recur; however, some people may have one outbreak and then never have another one. In between herpes outbreaks, the virus lies dormant (as if it is hibernating or sleeping) in nerve cells.

While exposure to HSV-1 is extremely common – as many as 90% of American adults have been exposed to the virus – and there is no stigma to having a cold sore, HSV-2 or genital herpes can cause embarrassment. Although there is no cure for genital herpes, an infected person can take steps to preventing spreading the disease and can continue to have a sex life.

While most herpes infections do not cause serious complications, infections in infants and in people with weakened immune systems or herpes infections that affect the eyes can be life-threatening.

Signs and Symptoms

HSV-1

Small, painful blisters filled with fluid around the lips or edge of the mouth
Tingling or burning around the mouth or nose (often a few days before blisters appear)
Fever
Sore throat
Swollen lymph nodes in neck

HSV-2

Small red blisters or open sores on genitals or inner thighs; in women, often occur inside the vagina
May be painful or not
In women, vaginal discharge
Fever, muscle aches
Headache Painful urination
Swollen lymph glands in the groin

Causes

HSV-1 is transmitted through saliva. Kissing, using the same eating utensils, sharing personal items (such as a razor), and receiving oral sex from someone who has HSV-1 can cause you to contract the virus.

HSV-2 is a sexually transmitted disease.

Both herpes viruses can be contagious even if the infected person does not have active symptoms or visible blisters.

Also, a mother can pass the infection to her baby during vaginal birth, especially if there are active blisters around the vagina at the time of delivery.

Risk Factors

Oral herpes (cold sores)

Everyone is at risk for oral herpes from HSV-1. In fact, studies suggest that by adolescence 62% of Americans are infected with HSV-1 and by the time people are in their 40s, 90% have been infected.

Genital herpes

All sexually active people are at risk for genital herpes. Having multiple sexual partners puts you at even greater risk. Women have a greater risk of being infected after sex with an unprotected partner than men do. Estimates of how many Americans are infected range from 20% to 30%.

Other factors

People with weakened immune systems, such as people with HIV/AIDS or those who take immunosuppressant drugs to treat an autoimmune disease or because of organ transplant, are at increased risk for severe cases of herpes.

Diagnosis

In many instances, your doctor is able to make the diagnosis of herpes from examining you and no tests are required. If your doctor is not 100% certain, however, then he or she make take a sample from the blisters to test for the virus. Finally, there is a blood test that may be helpful for making a diagnosis, especially if your doctor suspects herpes but you don't have an active infection.

Preventive Care

HSV-1

Avoiding kissing people with visible core sores
Don't share personal items
Wash your hands frequently
If you have HSV-1, be careful touching your eyes and genitals; don't perform oral sex on your partner
Use sunscreen
Reduce stress

HSV-2

Avoid having sex if you or your partner has an outbreak (active infection) of herpes. Herpes outbreaks are not always obvious and your partner may be contagious without you knowing it. Anyone involved in an ongoing sexual relationship with a partner infected with HSV-2 should get counseling from a healthcare practitioner on how to best keep yourself safe.
Avoid touching the sores
Use or have your partner use a latex condom (even when sores are not visible)
Limit the number of sex partners

Treatment Approach

Herpes cannot be cured, so the goals of treatment are to reduce the number of outbreaks and to lessen symptoms when you do have an outbreak.

Cold sores usually go away by themselves in no more than 1 to 2 weeks. Using medications may shorten the outbreak and decrease discomfort.

Antiviral medications for genital herpes can reduce outbreaks and help speed recovery when an outbreak does occur. They can also lessen the chances of spreading the virus.

Coping with the emotional and social aspects of having genital herpes is part of treatment. Relaxation techniques and support groups can help.

Lifestyle

For cold sores, applying either heat or cold to blisters may help relieve pain. Try ice or warm compresses.

For genital herpes, wear cotton underwear and avoid tight fitting clothes as they can restrict air circulation and slow the healing of lesions.

Be sure to tell your partner or potential partner that you have herpes.

Medications

Antiviral medicines - may help shorten the duration of a herpes outbreak and suppress recurring outbreaks. For genital herpes, there are two types of therapy: episodic and suppressive. With episodic therapy, you take medication at the first sign of an outbreak and for several days to shorten the duration or prevent a full outbreak. With suppressive therapy, you may take medication daily to keep outbreaks from occurring. Antiviral medications include:

Acyclovir (Zovirax)
Famciclovir (Famvir)
Valacyclovir (Valtrex)

Topical medications (for oral herpes) - include the antiviral cream Penciclovir (Denavir) and an over-the-counter cream, docosanol (Abreva).

Nutrition and Dietary Supplements

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider.

Lysine (1 to 3 g per day) - Although not all studies agree, several studies suggest that lysine may help reduce the number of recurring outbreaks of cold sores and possibly genital herpes. Most of the studies have involved people with cold sores or with both cold sores and genital herpes. A few studies also suggest that lysine may help shorten the duration of an outbreak. The evidence is somewhat stronger for cold sores: the research to date is not entirely conclusive, lysine supplements have been used to help treat or prevent mouth and genital lesions caused by herpes. Taking lysine supplements or increasing lysine in your diet (from foods like fish, chicken, eggs, and potatoes) may speed recovery time and reduce the chance of recurrent breakouts of the herpes infection. If you have high cholesterol, heart disease, or high triglycerides (type of fatty material in the blood, generally measured when you have your cholesterol checked), it is best, at this point, not to use lysine because animal studies suggest that this supplement may raise cholesterol and triglyceride levels.
Propolis - A resin made by bees, propolis is loaded with flavonoids (antioxidants that help fight infection and boost immune function). Test tube studies show it can stop HSV-1 and HSV-2 from reproducing. One small study of people with genital herpes compared an ointment made from propolis to Zovirax ointment. People using propolis saw the lesions heal faster than those using topical Zovirax. More studies are needed to say for sure whether propolis works.
Zinc - In test tubes, zinc is effective against HSV-1 and HSV-2. In one small study in people, those who applied zinc oxide cream to cold sores saw them heal faster than those who applied a placebo cream.

Herbs

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

Lemon balm (Melissa officinalis) - Several studies suggest that topical ointments containing lemon balm may help heal cold sores. In one study, for example, those who applied lemon balm cream to their lip sores saw a reduction in redness and swelling after two days.
Aloe (Aloe vera) - Preliminary evidence suggests that aloe gel used topically may improve the symptoms of genital herpes in men. In two studies, men who used the aloe vera cream (0.5% aloe) saw lesions heal faster than those who used a placebo cream. It isn't know whether aloe vera would also help heal cold sores.
Rhubarb cream (Rheum palmatum) - In one Swiss study, a cream made from sage (Salvia officinalis) and rhubarb was as effective as Zovirax in healing cold sores. Sage by itself was not beneficial. More research is needed.
Eleutherococcus or Siberian ginseng (Eleutherococcus senticosus/Acanthopanax senticosus) -Although not all studies agree, one 6-month study of 93 people with genital herpes found that Siberian ginseng reduced the frequency, severity, and duration of outbreaks. This herb should not be taken if you have high blood pressure, obstructive sleep apnea (repeated, prolonged periods when breathing stops while sleeping), narcolepsy (frequent day time sleeping), are pregnant or breastfeeding.
Peppermint oil (Mentha x piperita ) - In test tubes, peppermint oil has stopped a number of viruses from reproducing, including herpes. However, it isn't known whether peppermint oil would have any effect on the herpes virus in humans.

Homeopathy

Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the remedies described below for the treatment of herpes based on their knowledge and experience. One study of 53 people with genital herpes did show that the majority had improvement in their symptoms and were less likely to have recurrent outbreaks when treated with homeopathy. Participants in this study were followed for up to 4 years.

Before prescribing a remedy, homeopaths take into account a person's constitutional type. A constitutional type is defined as a person's physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for each individual.

For cold sores:

Natrum muriaticum - for eruptions at the corners of the mouth that occur during periods of emotional stress and tend to worsen in the daytime
Rhus toxicodendron - for eruptions consisting of many small blisters that itch intensely at night
Mercurius - for children who drool and may have a fever
Sepia - for outbreaks that do not improve with other homeopathic remedies; this remedy is most appropriate for individuals who tend to have a lack of energy and don't tolerate cold weather

For genital lesions:

Graphites - for large, itchy lesions in individuals who are overweight
Natrum muriaticum - for eruptions that occur during periods of emotional stress and symptoms that tend to worsen in the daytime
Petroleum - for lesions that spread to anus and thighs; symptoms tend to worsen in winter and improve in summer
Sepia - for outbreaks that do not improve with other homeopathic remedies; this remedy is most appropriate for individuals who tend to have a lack of energy and don't tolerate cold weather

Mind/Body Medicine

Support groups - Having genital herpes can impact your social and emotional life. In fact, if you have herpes, it is quite common to feel depressed, angry, and even guilty. Worrying about possible rejection by someone with whom you are hoping to become intimate is also typical. Joining a support group where members share experiences and problems can help relieve the stresses associated with having genital herpes. If you are in a committed relationship, seeing a couples' therapist with your partner may also be helpful.
Relaxation techniques - Using relaxation techniques, such as yoga, guided imagery, and meditation, on a daily basis may help you feel better overall and cope with stresses related to having herpes.
Self-hypnosis - Self-hypnosis using guided imagery may also help relieve stress. In one 6-week training program, participants with frequently recurring genital herpes were able to reduce outbreaks by nearly 50% and improve their mood, including reducing feelings of depression and anxiety.
Other - Individual therapy with a psychiatrist, psychologist, or social worker; and techniques such as biofeedback can help reduce emotional symptoms associated with herpes.

Other Considerations

Pregnancy

Herpes viruses can be transmitted to a newborn during vaginal delivery, especially if the mother has active lesions in the vagina at the time of delivery. Herpes infections in newborns can be life-threatening or cause disability. Delivery by cesarean section (C-section) will be recommended to avoid infecting the baby.

Special Populations

Newborns – herpes infections contracted during delivery from the mother can lead to meningitis, herpes infection in the blood, chronic skin infection, and may even be fatal.

You are more likely to have severe, frequent outbreaks and to experience complications from herpes if your immune system is suppressed from:

HIV or AIDS
Chemotherapy for cancer
Long-term use of high doses of corticosteroids
Medications that intentionally suppress the immune system

Warnings and Precautions

If you are diagnosed with genital herpes, you should be tested for other sexually transmitted diseases such as chlamydia and gonorrhea.

Prognosis and Complications

Herpes is a chronic, recurrent infection. The initial symptoms usually appear within 1 to 3 weeks of exposure to the virus and last 7 to 10 days (for cold sores) or 7 to 14 days (for genital lesions). Usually the number of outbreaks is greatest in the first year and higher for HSV-2 genital lesions than HSV-1 cold sores. Each year after that, the number of outbreaks usually goes down and they become less severe. But you can never completely get rid of the virus.

Complications of herpes include:

Herpetic keratitis – herpes infection of the eye leading to scaring within the cornea and possible blindness
Persistent herpes infection, without lesion-free periods
Herpes infection in the esophagus
Herpes infection of the liver which can lead to cirrhosis (liver failure)
Encephalitis and/or meningitis (serious brain infections)
Lung infection
Eczema herpetiform – widespread herpes across the skin

Supporting Research

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Review Date:
12/23/2007
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

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