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Bipolar disorder

Highlights

Drug Approval

Quetiapine (Seroquel) has been approved for treatment of bipolar depression. Quetiapine is now the only drug approved for treating both manic and depressive states of bipolar disorder.

Drug Warning

The anti-seizure drug lamotrigine (Lamictal) can cause cleft lip and palate birth defects if taken during the first trimester of pregnancy.

Bipolar Disorder in Children and Adolescents

• The course of bipolar disorder is different in young people than in adults, indicates a 2006 study in the Archives of General Psychiatry. The study found that symptoms in children and adolescents last longer and fluctuate more rapidly than those in adults.
• Atypical antipsychotic drugs are being increasingly prescribed to pediatric patients despite the lack of evidence concerning their long-term safety and effectiveness, notes a 2006 study in the Archives of General Psychiatry.

Economic Burden of Bipolar Disorder

Major depressive disorder may be six times more common than bipolar disorder, but bipolar disorder costs twice as much in lost productivity, according to a 2006 study in the American Journal of Psychiatry. Much of this lost productivity is due to poor functioning in the workplace, which is caused more by the disorder’s depressive episodes than its manic ones.

Collaborative Care for Patients

A disease management model similar to those used for treating diabetes and asthma may be the best way to help patients with bipolar disorder control their symptoms, stick to their medication, and improve their social relations and quality of life. This treatment model includes patient education by nurses, as well as pharmacological treatment by psychiatrists.

Bipolar Disorder and High Blood Pressure

Patients with bipolar disorder may be at increased risk of developing high blood pressure (hypertension), suggests a 2006 study in the Journal of Affective Disorders. Researchers found a higher rate of hypertension among people with bipolar disorder, and those with anxiety, than in the general population.

Introduction

Bipolar disorder, or manic-depressive illness, is characterized by moods that swing between two opposite poles:

• Periods of mania with exaggerated euphoria, irritability, or both
• Episodes of depression

Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental, and other factors.

Bipolar Disorder Categories

Bipolar disorder is classified according to the pattern and severity of the symptoms as bipolar disorder I, bipolar disorder II, or cyclothymic disorder. Patients with one type may develop another. Nevertheless, they are distinct enough to merit separate classifications, and some experts believe these conditions are actually separate disorders with different biologic factors that account for their differences.

Bipolar Disorder I. Bipolar disorder I is characterized by at least one manic episode, with or without major depression. In 60 - 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories.

Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week, and it can last for months. Typically, depressive episodes tend to last 6 - 12 months, if left untreated.

Bipolar Disorder II and Hypomania. Bipolar disorder II is characterized by predominantly depressive symptoms with occasional episodes of hypomania. Hypomania is similar to mania, but the symptoms (typically euphoria) are less severe and do not last as long.

Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.

Cyclothymic Disorder. While cyclothymic disorder is not as severe as either bipolar disorder II or I, the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. (One report, in fact, referred to these patients as having "darker" natures while bipolar II patients were "sunnier.")

The disorder lasts at least 2 years, with single episodes persisting for more than 2 months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.

Course of the Illness

Bipolar disorder can be severe and long-term, or it can be mild with infrequent episodes. Patients with the disease may experience symptoms in very different ways. A typical bipolar disorder patient averages 8 - 10 manic or depressive episodes over a lifetime. However, some people experience more and some fewer episodes.

Typical Bipolar Cycles. In most cases of bipolar disorder, the depressive phases far outnumber manic phases, and the cycles of mania and depression are neither regular nor predictable. Many patients, in fact, experience mixed mania, or a mixed state, in which both mania and depression coexist.

Rapid Cycling. About 15% of patients with the disorder have a temporary, complicated phase known as rapid cycling. With this phase the manic and depressive episodes alternate at least four times a year and, in severe cases, can even progress to several cycles a day. Rapid cycling tends to occur more often in women and in those with bipolar II. Typically, rapid cycling starts in the depressive phase, and frequent and severe episodes of depression may be the hallmark of this event. This phase is difficult to treat, particularly since antidepressants can trigger the switch to mania and set up a cyclical pattern.

Differences Between Children and Adults. An important 2006 study indicated that children and adolescents with bipolar disorder experience a very different disease course than adults. The symptoms of children tend to last longer than adults, and their mood swings change more rapidly. Young patients may also be more likely than adults to convert from one bipolar subtype to another, for example from unspecified bipolar to bipolar I or II. The study also suggested that patients whose bipolar disorder emerged in their pre-teen years tend to display more symptoms than those whose illness began in their teens.

Risk Factors

Between 1 - 2 million Americans are thought to suffer from bipolar disorder. Estimates of the lifetime risk for the disorder run are about 1.25%. There is some indication that the incidence of bipolar disorder may be increasing, but more research is needed to confirm this.

Gender

Bipolar disorder affects both sexes equally, but there is a higher incidence of rapid cycling, mixed states, and cyclothymia in women. Early-onset bipolar disorder tends to occur more frequently in men and it is associated with a more severe condition. Men with bipolar disorder also tend to have higher rates of substance abuse (drugs, alcohol) than women.

Age

Bipolar disorder is the most common psychotic disorder, and experts believe that it occurs in 1% of people among all age groups.

Early-Onset Bipolar Disorder. In one survey, 59% of bipolar disorder patients had their first symptoms when they were children or adolescents. Typically, there was a very long delay until the condition was diagnosed and treated. Bipolar symptoms in young people closely mimic those in adulthood, but may have slight differences:

• The initial episodes are more likely to be depressive. A study reported that 33% of children who experienced major depression developed bipolar I by age 21 and 15% of them had bipolar II disorder.
• Manic phases usually begin in adolescence or young adulthood, with an average age of onset being 18 years. Mood often involves irritability, but in general symptoms, resemble those seen in adults (euphoria and grandiosity, flight of ideas, racing thoughts, and a decreased need for sleep).

Early-onset bipolar disease is also associated with the following characteristics:

• A family history of bipolar disorder is usually present. Children with bipolar disorder who have one or more parents with the same disorder often have a more severe form than does the affected parent.
• A higher rate of co-existing conditions such as panic disorder, conduct disorder, substance abuse, suicidal behavior, and psychotic symptoms may occur during bipolar episodes. Young patients are at higher risk for these complications regardless of the presence or absence of supportive parents.
• The condition is often more severe in children than in adult patients, with a higher risk for mixed mania (simultaneous depression and mania), multiple and frequent cycles, and a long duration of illness without well periods.

Adult-Onset Bipolar Disorder. Bipolar disorder can also appear for the first time in people over the age of forty. In fact, age 40 is another peak of onset for women.

Onset Late in Life. Bipolar disorder that occurs late in life often either follows many years of repeated episodes of unipolar depression or it accompanies medical and neurological problems (particularly cerebrovascular disease, such as stroke). It is less likely to be associated with a family history of the disorder than earlier-onset bipolar disorder.

Accompanying Neurologic or Emotional Disorders

Patients with bipolar disorder, especially type II or cyclothymic disorder, have frequent episodes of major depression. Anxiety disorders also commonly coexist in these patients. For example, the occurrence of panic disorder in patients with bipolar disorder is 26 times that of the general population. Patients with bipolar disorder, particularly those with type II, are also subject to phobias. In one study, the presence of anxiety disorders was also associated with longer and more severe bipolar depressive episodes and with a higher risk for suicide.

Symptoms of bipolar disorder in children are often confused with attention-deficit hyperactivity disorder (ADHD). Furthermore, the two conditions can coincide. In one study, 65% of adolescents with bipolar disorder met criteria for ADHD. Yet another study indicated that close to 25% of children diagnosed with ADHD either already had bipolar disorder or go on to develop it. The risk for both diagnoses is highest in white males. Symptoms are also more severe in people with both conditions. Some experts believe that many of these disorders may actually be variations of a single disease.

Family History

Bipolar disorder frequently occurs within families, although genetic factors account for only about 60% of cases. Family members of patients with bipolar disorder also have a higher than average incidence of other psychiatric problems. They include schizophrenia, schizoaffective disorder, anxiety disorders, ADHD, and major depression.

Causes

No single cause may ever be found for bipolar disorder. Instead, a combination of biologic, genetic, and environmental factors appears to trigger and perpetuate the chemical imbalances in the brain that shape this complex disorder. Biologic factors observed or considered in bipolar disorder, as detected by use of imaging scans and other tests, include:

• Oversecretion of cortisol, a stress hormone
• Excessive influx of calcium into brain cells
• Abnormal hyperactivity in parts of the brain associated with emotion and movement coordination
• Low activity in parts of the brain associated with concentration, attention, inhibition, and judgment.
• A superfast "biologic clock"

The so-called biologic clock is a tiny cluster of nerves called the supra chiasmatic nucleus, or SCN. The SCN is located in the center of the brain in the hypothalamus region. It regulates a person's circadian rhythm, the daily cycle of life, which influences sleeping and waking.

Biologic and Genetic Factors Shared with Other Disorders

The genetics of bipolar disorder are the most intensively studied of all psychiatric diseases. Multiple genes, involving several chromosomes, have been linked to its development. Bipolar disorder also may share these genetic factors with other disorders, including schizophrenia, epilepsy, and panic disorder. It is not clear if some of these disorders are variations of a single disease or separate disorders.

Bipolar Disorder and Schizophrenia. Researchers have been investigating whether common biologic factors are involved with schizophrenia, severe bipolar disorder, and other psychoses. Schizophrenia and bipolar disorder often show up in the same family. Researchers are identifying a number of common genetic and biologic pathways that they both share. Some examples of studies comparing biologic differences and similarities include:

• Genetic abnormalities for both diseases appear on many of the same chromosomes. Locations on chromosomes 1, 6, 8, 12, and 22 have been identified as gene regions linked to bipolar disorder.
• Pathways of the neurotransmitter dopamine appear to be important in both illnesses. (A neurotransmitter acts as a chemical messenger between nerve cells.)
• Blood levels of reelin, a protein in the brain, may be useful as markers for both schizophrenia and bipolar disorder, although levels vary between the two diseases. (Reelin is a protein that is important for information processing.)
• Elevated levels of vesicular monoamine transporter (VMAT2) have been observed in the brainstems of patients with both bipolar disorder and schizophrenia. VMAT2 is a protein in the brain that regulates the transport of important neurotransmitters. The distribution of this protein in the brain, however, differs between the two diseases.
• In one study of people with bipolar disorder, the left side of the hippocampus was significantly larger than it was on the right. In patients with schizophrenia, the hippocampus' volume was decreased. (The hippocampus is located deep in the brain and stores memory.)

Bipolar Disorder and Epilepsy.Neurotransmitters called gamma aminobutyric acid (GABA) and norepinephrine have been implicated in mania:

• GABA helps prevent nerve cells from over-firing
• Norepinephrine is a hormone that involves stress

Some research has associated similar biologic mechanisms in patients with epilepsy and bipolar disorder. As in epilepsy, the more episodes a bipolar disorder patient experiences early in the course of the disease, the more frequent and severe later episodes will be. Antiseizure drugs, in fact, can play an important role in the treatment of bipolar disorder.

Panic Disorder and Bipolar Disorder.Researchers are also studying the common biologic and genetic factors between panic disorder and bipolar disorder. While specific genes have not yet been identified, some researchers studying these illnesses now believe that they may represent different forms of a shared, complex condition.

Prognosis

Medical evidence has shown that patients with bipolar disorder have higher death rates from suicide, heart problems, and death from all causes than those in the general population. Patients who get treatment, however, experience great improvement in survival rates, including deaths from suicide and heart disease.

Suicide

The risk for suicide is very high in patients who suffer from bipolar disorder and who do not receive medical attention. Between 10 - 15% of patients with bipolar disorder I commit suicide, with the risks being highest during episodes of depression or mixed mania (simultaneous depression and mania). Some studies suggest that the risk for suicide in patients with bipolar disorder II is even higher than it is for those with bipolar disorder I or major depressive disorder. Patients who also suffer from an anxiety disorder, are also at greater risk for suicide. (Rapid cycling, although a more severe variation of bipolar disorder, does not appear to increase the suicide risk in patients with bipolar disorder.)

Many pre- and early adolescent children with bipolar disorder are more severely ill than are adults with the disease. According to a 2001 study, 25% of children with bipolar disorder are seriously suicidal. They have a higher risk for mixed mania, multiple and frequent cycles, and a long duration of illness without well periods.

Thinking and Memory Problems

Studies suggest that patients with bipolar disorder may have varying degrees of problems with short- and long-term memory, speed of information processing, and mental flexibility. Such problems persist even between episodes. They tend to be more severe when a person has more manic episodes. Medications used for bipolar disorder could be responsible for some of these abnormalities, although some evidence suggests that such traits may have a biologic basis. These mental difficulties may make it harder for these patients to comply with medications or to participate in complex psychotherapies.

Behavioral and Emotional Effects of Manic Phases on the Patient

A small percentage of bipolar disorder patients demonstrate heightened productivity or creativity during manic phases. More often, however, the distorted thinking and impaired judgment that are characteristic of manic episodes can lead to dangerous behavior, including:

• Spending money with reckless abandon, causing financial ruin in some cases
• Angry, paranoid, and even violent behaviors
• Openly promiscuous behavior

Such behaviors are often followed by low self-esteem and guilt, which are experienced during the depressed phases. During all stages of the illness, patients need to be reminded that the mood disturbance will pass and that its severity can be diminished by treatment.

Substance Abuse

Cigarette smoking is prevalent among patients with bipolar disorder, particularly those who have frequent or severe psychotic symptoms. Some experts speculate that, as in schizophrenia, nicotine use may be a form of self-medication because of its specific effects on the brain.

Up to 60% of patients with bipolar disorder abuse other substances (most commonly alcohol, followed by marijuana or cocaine) at some point in the course of their illness.

The following are risk factors for alcoholism and substance abuse in patients with bipolar disorder:

• Having mixed-state episodes rather than ones of pure mania
• Being a man with bipolar disorder

Effects on Loved Ones

Patients do not manifest their negative behaviors (such as spending sprees or even becoming verbally or physically aggressive) in a vacuum. They have a direct effect on others around them. It is very difficult for even the most loving of families or caregivers to be objective and consistently sympathetic with an individual who periodically and unexpectedly creates chaos around them.

Many patients and their families find it difficult to accept that these episodes are part of an illness and not simply extreme, but normal, characteristics. Such denial is often strengthened by patients who are highly articulate and deliberate, and who can intelligently justify their destructive behavior, not only to others, but also to themselves.

Family members may also feel socially alienated by the fact of having a relative with mental illness, and feel forced to conceal this information from acquaintances.

Economic Burden

The economic burden of bipolar disorder is significant. It is estimated that the disorder costs the U.S. workplace about $14.1 billion annually in lost productivity, mostly due to poor functioning on the job. According to a 2006 study sponsored by the U.S. National Institute of Mental Health, bipolar disorder accounts for twice as much lost productivity as major depressive disorder (MDD), despite the fact that MDD is more prevalent. Each worker with bipolar disorder loses about 66 workdays a year compared with 27 workdays a year for workers with MDD. Research suggests that bipolar disorder’s depressive episodes impair productivity more than its manic episodes.

Association with Physical Illnesses

People with mental illness have a higher incidence of many medical conditions, including heart disease, asthma and other lung problems, gastrointestinal disorders, skin infections, diabetes, hypertension, migraine headaches, hypothyroidism, and cancer. Patients with bipolar disorder are also less likely to receive medical care than people without mental disorders. Substance abuse, including smoking, alcoholism, and drug abuse, also contributes to many of these problems as well as reduced access to care. Medications used for bipolar disorder can also increase the risk for medical problems.

However, people with bipolar disorder and other mental illness have a higher risk for a number of these conditions independent of these factors.

Diabetes. Diabetes is diagnosed almost three times more often in people with bipolar disorder than it is in the general population. A 2002 study reported that 58% of patients with bipolar disorder were overweight, with 26% meeting the criteria for obesity. Being overweight is a significant risk factor for diabetes and so it may be the common factor in both diseases. Drugs used to treat bipolar can also cause weight gain and diabetes. Common genetic factors in diabetes and bipolar disorder may cause a rare disorder called Wolfram syndrome and other problems with carbohydrate metabolism.

High Blood Pressure. Patients with bipolar disorder may be at a higher risk for high blood pressure (hypertension) than patients without the disorder. The high prevalence of hypertension among patients with bipolar disorder may also account for their greater risk for illness and death from heart-related conditions.

Migraine Headaches. Migraines are common in patients with a number of mental illnesses, but they are particularly common among patients with bipolar II disorder. In one study, 77% of patients with bipolar II had migraines compared with 14% of patients with bipolar I, suggesting that different biologic factors may be involved with each bipolar form.

Hypothyroidism. Hypothyroidism (low thyroid levels) is a common side effect of lithium, the standard treatment for bipolar. However, evidence also suggests that patients, particularly women, may be at higher risk for low thyroid levels regardless of which medications they use. Hypothyroidism may, in fact, be a risk factor for bipolar disorder in some patients.

Diagnosis

Bipolar disorder is more common than previously thought, but this illness, particularly bipolar disorder II, is still poorly recognized in the family-practice setting. It is estimated that only a third of affected people are accurately diagnosed.

Ruling Out Similar Conditions

When making a diagnosis of bipolar disorder, it is important that the doctor rule out other conditions that may be causing symptoms of bipolar disorder.

Distinguishing Mania from Normal Euphoria or Joy. A major difficulty with a diagnosis of bipolar disorder is the tendency for a patient to be unable to recognize his or her own condition, particularly when in the manic state. The patient often denies their symptoms, which may be perceived as positive feelings. The doctor should take a careful and complete history of any and all episodes of depression, mania, or both. Hypomania, the less severe variant of mania, may be particularly difficult to distinguish from normal joy or euphoria. It can often be distinguished by the following characteristics:

• Hypomania persists for at least 4 days
• Patients with hypomania are easily distracted and overly talkative
• Patients with hypomania have difficulty functioning

Distinguishing Unipolar from Bipolar Depression. People with bipolar disorder are more likely to seek help because of a depressive episode. Indeed, about 16% of people with bipolar disorder do not have a manic episode until they have experienced three or more depressive episodes. In such cases, the condition is often diagnosed as major depression. An accurate diagnosis is important because patients with bipolar disorder who are inappropriately medicated solely with antidepressants have a higher incidence of rehospitalization than do other bipolar disorder patients.

Bipolar disorder should be suspected in patients who have been treated for depression and who had a fast and good response, followed by the return of depression and failure to respond to other antidepressant treatment.

A family history of manic-depressive illness may make a doctor suspicious, but a diagnosis of bipolar disorder cannot be established until a manic or hypomanic episode has occurred. Patients with bipolar II disorder and those with depressive mixed state are most likely to be misdiagnosed with depression.

Attention Deficit Hyperactive Disorder (ADHD). Children or adolescents with bipolar disorder may be inappropriately diagnosed with attention-deficit hyperactivity disorder. ADHD and bipolar disorder often cause inattention and distractibility, and the two disorders may be difficult to distinguish, particularly in children. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary distinction between bipolar disorder and ADHD is the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not those with ADHD.

Schizophrenia. Severe manic episodes that include delusions and hallucinations may be easily confused with schizophrenia. (African-American men are more likely to be diagnosed with schizophrenia than with bipolar disorder.) The key factors that distinguish bipolar disorder from schizophrenia include:

• The presence of one or more manic or hypomanic episodes in bipolar disorder, but not in schizophrenia
• A flat emotional expression, with no variability in the voice among people with schizophrenia
• People with bipolar disorder are typically very expressive

Substance Abuse. Up to 60% of patients with bipolar disorder abuse alcohol and drugs at some point during their illness. Both diagnosis and treatment are difficult in such cases, since substance abuse is often a method of self-treatment, and withdrawal can produce symptoms of mania or severe depression. The effects of cocaine in a heavy user can also produce abnormal mood swings that closely resemble those of bipolar disorder.

Other Causes of Mood Swings. Other conditions that can cause mood swings include:

• Thyroid disorders
• Adrenal disorders (Addison's disease or Cushing's syndrome)
• Vitamin B12 deficiency
• Neurologic disorders such as Huntington's disease, epilepsy, brain tumors, encephalitis, or multiple sclerosis
• Medications, including corticosteroids and certain drugs used to treat anxiety and Parkinson's disease

Laboratory Tests

Patients should be tested for drugs or alcohol if the doctor suspects that they have been using these substances. Blood tests for thyroid function should also be performed.

Imaging Tests

Noninvasive imaging tests of the brain using magnetic resonance imaging (MRI) and positron-emission tomographic (PET) scans are being used in clinical trials for detecting abnormalities in the brain. The results of these tests may eventually help identify bipolar disorder and test the effectiveness of various treatments.

Treatment

Bipolar disorder is a recurrent disease that can be unpredictable. The major goals of treatment are to:

• Treat and reduce the severity of acute episodes of mania or depression when they occur
• Reduce the frequency of episodes
• Avoid cycling from one phase to another
• Help the patient function as best as possible between episodes

The doctor will first try to determine what may have triggered the attack and identify any accompanying medical or emotional problems that might interfere with or complicate treatment.

Some experts think that the best way to treat bipolar disorder is through a disease management model, similar to those used for treating diabetes and asthma. In this “collaborative care” model, patients are treated by a multi-disciplinary team of psychiatrists and nurses. The nurses provide patient education on medication side effects, early warning signs of symptoms, and coping skills. In several 2006 studies, patients who received this treatment model reported fewer symptoms, more productive time at work, better relationships with family members, and general improvement in quality of life.

Challenges of Bipolar Treatment

The treatments for bipolar disorder, while very effective, pose some specific challenges for the patient:

• Mood variations in bipolar disorder are not predictable, so it is sometimes difficult to tell if a patient is responding to treatment or naturally emerging from a bipolar phase.
• A patient with bipolar disorder cannot always reliably inform the doctor about the state of the illness.
• The patient is likely to need more than one medication during the course of the disease. This increases the risk for distressing side effects. Noncompliance is common.
• Patients often have more than one medical problem and need different drugs to treat each condition. Such medications may interact with drugs used to treat bipolar disorder or increase side effects. For example, children with bipolar disorder have a higher risk for attention deficit-hyperactivity disorder, which is treated with stimulants that can complicate bipolar treatment.
• Family members who have not been educated about the disorder may interfere with the treatment.
• Treatment strategies for children and the elderly have not been intensively studied and have not been clearly defined.
• Treatments may be costly.

Specific Drugs and Other Treatments Used in Bipolar Disorder

The following are the treatment options for most patients with bipolar disorder, depending on the bipolar disorder phase or episode. Patients should understand that, even with aggressive therapy, either mania or depression recurs in almost three-quarters of patients.

Drugs Used in Bipolar Disorder. Mood stabilizing drugs are the mainstay for patients with bipolar disorder. They are defined as drugs that are effective for acute episodes of mania and depression and that can be used for maintenance. The standard first-line mood stabilizers are lithium and valproate. Both drugs stimulate the release of the neurotransmitter glutamate, although they appear to work through different mechanisms. Other drugs may also be used.

• Lithium. Lithium has been used for years for bipolar disorder. It remains the best drug for people with pure mania characterized by euphoria and pure depression. Although imperfect, it is also an effective long-term drug for many patients with other bipolar subtypes.
• Antiseizure Drugs. Valproate (valproic acid) is an anti-seizure drug that works well for many patients with mania, rapid-cycling, and mixed states, as well as for patients who are substance abusers. Carbamazepine (Tegretol, Carbatrol, Equetro) or oxcarbazepine (Trileptal) is usually the second anti-seizure medication of choice. Lamotrigine (Lamictal), a newer antiseizure drug, is proving to be an effective mood-stabilizer and may work better for depressive episodes than lithium. It appears to be particularly helpful for patients with rapid cycling and bipolar II disorder, in whom depression remains problematic after taking other mood stabilizers. Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
• Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Clozapine (Clozaril) was the first of these drugs, but it has not yet been approved for treatment of bipolar disorder. The newer atypical antipsychotics include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and ariprazole (Abilify). These five drugs have all been approved for treatment of bipolar mania and, with the exception of quetiapine, mixed episodes. Quetiapine is approved for treatment of both manic and depressive states. Olanzapine is the only atypical approved for bipolar maintenance treatment. A combination olanzapine and fluoxetine drug (Symbyax) is also approved for treatment of bipolar depression.

Such drugs may be used in combination with each other. Additional drugs, such as conventional antipsychotics, antidepressants, antianxiety drugs, or experimental drugs are used as necessary.

Electroconvulsive Therapy. Electroconvulsive therapy is a very effective treatment that may be administered in certain patients for acute episodes or for maintenance.

Non-Medical Treatments. In addition to medical treatments, psychotherapy and sleep management are also extremely parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), an ongoing trial supported by the National Institute of Mental Health, is the largest treatment study ever conducted for bipolar disorder. With plans to enroll approximately 5,000 patients, STEP-BD aims to evaluate all the best-practice treatment options used for bipolar disorder, including mood-stabilizing medications, antidepressants, and atypical antipsychotics. It will also evaluate psychosocial interventions, including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and psychoeducation. Results of STEP-BD may clarify the best treatments for bipolar disorder.

Treatment Guidelines for Acute Manic Episodes

Step 1. Determine the Need for Hospitalization and Eliminate Triggers. The first step in treating an acute manic episode is to rule out any life-threatening conditions and eliminate any triggers, such as antidepressants or other substances that can elevate moods.

Patients often require hospitalization at the onset of acute mania. The need for hospitalization depends on a number of factors:

• Whether the patient is at risk for suicide or for harming others
• The availability of social and emotional support at home

Step 2. Control Symptoms of Acute Manic with a Mood Stabilizer. Doctors often try different drugs to control a manic episode. If a current drug does not work well, another type of drug may be added or substituted. It may take several weeks for a mood stabilizer to take effect and other drugs may be needed.

The following is an example of a stepped approach recommended by some experts:

• Initiating a mood-stabilizing drug is the critical first step. Either valproate or lithium is the standard first drug for most manic episodes. Lithium is effective in 60 - 80% of all hypomanic and manic episodes. Carbamazepine is usually used in place of valproate to treat patients with multiple manic episodes, mixed episodes, and rapid cycling. Combinations of these mood stabilizers may be used if the patient does not respond to a single drug.
• If the patient does not respond fully within a week, atypical antipsychotics may be added to one or more mood stabilizers. Atypicals include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), apriprazole (Abilify), and ziprasidone (Geodon). Clozapine (Clozaril), the oldest atypical drug, also works well but it is not generally used because of its potential for severe side effects and the need for weekly monitoring of white blood cell counts.

Step 3. Addition of Other Treatments. Other treatments may be added to speed recovery, treat any psychosis, and achieve remission. They include:

• Standard antipsychotic drugs (also called neuroleptics), such as haloperidol (Haldol). These drugs may be used for acute mania. They can cause severe side effects, however, particularly extrapyramidal effects, which disrupt motor control. They are not generally used on a long-term basis for treating bipolar disorder.
• Benzodiazepines, such as clonazepam (Klonopin) or lorazepam (Ativan), are anti-anxiety drugs that may be particularly beneficial if the patient is experiencing severe mania.
• Electroconvulsive therapy. This treatment helps patients who do not respond to medication and may even be life-saving in elderly patients with severe late-onset mania.

Step 4. Terminate Some Drug Treatments. Drugs may be stopped under the following circumstances:

• When side effects are intolerable
• When the patient does not respond to the maximum dose
• When the patient improves and recovery is sustained

In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.

Step 5. Continuation of Mood Stabilizers. Mood stabilizers are typically continued for about 8 weeks, unless the patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.

Treatment Guidelines for Depressive Episodes

Depressive episodes pose a particular challenge. They are a significant cause of suffering, yet the use of standard antidepressants poses a significant risk for triggering mania. It is also not clear if standard antidepressants work for bipolar depression. In fact, depressive episodes are so difficult to treat that some experts advise patients who do not respond to mood stabilizers to simply expect to endure the depressive episode for about 2 - 3 months.

Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.

If improvement does not occur within 2 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).

Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to “switch” to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.

Alternative: Atypical Antipsychotics. An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the FDA approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax is the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.

Psychotherapy. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors.

Other Treatments. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches. Antipsychotic medication may be needed for severely depressed and delusional patients. Small studies indicate that a subgroup of patients may respond to thyrotropin-releasing hormone, a substance that regulates thyroid hormones.

Treatment Guidelines for Mixed Episodes and Rapid Cycling

The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism, which may have caused this condition. Many patients may require a combination of medications to control rapid cycling.

• Antidepressants may prompt rapid cycling and should be tapered off.
• Lithium or valproate is a first-line treatment for rapid cycling.
• Lamotrigine is an alternative treatment for rapid cycling.
• Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
• One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
• Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
• Electroconvulsive therapy can be useful in emergency situations.

In addition, other measures should be taken:

• Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
• Patients should avoid exposure to bright light.
• All efforts should be made to help the patient sleep normally.

Treatment Guidelines for Maintenance

Drugs Used During Maintenance. Relapse occurs in most patients after treatment of acute attacks, and patients who are at high risk for recurring episodes should consider life-long maintenance therapy. This usually involves mood-stabilizing drugs.

• Lithium is a first-line mood stabilizer used in maintenance therapy. The anti-epileptic drug valproate is also a first-line treatment. In general, the two work equally well, although valproate may be better for patients who have had multiple manic episodes. There are some differences in side effects, but the drop-out rates between the drugs are similar. Lithium has proved effective for preventing relapses of manic episodes, but may not work as well for controlling depressive symptoms.
• Lamotrigine, an anti-epileptic drug, was approved in 2003 for long-term maintenance treatment. It is also used as a first-line drug for treating depressive episodes.
• Carbamazepine and oxcarbazepine are other anti-epileptic drugs used as alternative maintenance treatments.
• Atypical antipsychotics may be used for maintenance, particularly in combination with a mood stabilizer. In 2004, olanzapine became the first atypical antipsychotic to be approved specifically for maintenance treatment.

The general recommendations for maintenance therapy with lithium are as follows:

• The earlier lithium is started in the disease process, the better. Studies suggest that patients on long-term lithium therapy have survival rates comparable to the general population, but those who permanently drop out of therapy have significantly lower survival rates. In one study, patients who stopped taking it increased their risk of suicide in the first year by 20 times.
• Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
• For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.

Treatment Guidelines for Children and Adolescents

Doctors are still trying to decide the best treatment of bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be even more severe in younger people. Parents should consider the potential risks and benefits of treatment for their children.

Lithium and valproate are first-line treatments. Alternative treatments include the antiseizure drug carbamazepine or atypical antipsychotics (olanzapine, quetiapine, risperidone). If the patient does not respond to lithium or valproate treatment, one of these other drugs may be substituted. If treatment with a single drug does not work, a combination of these drugs may be used.

Lithium and valproate are the drugs most studied in children and adolescents. Some evidence suggests that larger rather than smaller doses of valproate or lithium may work best. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate).

Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.

Psychotherapy is an important addition to drug treatment. Therapy that includes the entire family is also important.

Medications

Lithium

Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) is one of the standard mood stabilizing drugs for bipolar disorder. Lithium is extremely helpful for most patients and it significantly reduces the rate of hospitalizations in bipolar disorder. Some studies report the following advantages of lithium:

• Lithium is effective in 60 - 80% of all hypomanic and manic episodes. (Valproate may be better in patients with multiple manic episodes, mixed episodes, and rapid cycling.)
• It helps to prevent relapses.
• It helps psychosocial functioning.
• It may help reduce the risk for suicide regardless of its effects on stabilizing mood.
• It may act directly on the nerve clusters affecting the circadian rhythm and slow down the cycle of this "biologic clock." (There is some evidence that patients with bipolar disorder have a faster biologic clock.)
• It works well for most patients even if they have discontinued taking it and wish to restart treatment.

Administration of Lithium. Lithium may take weeks to become totally effective, so patients should not expect an immediate response during an acute episode. Doctors may take different approaches to administering the drug:

• Some doctors initially administer lithium in two low doses and gradually increase the dosage over time until an effective (therapeutic) level is achieved.
• Another approach is to administer a higher dose initially and measure blood levels of the drug after 24 hours. The doctor uses this information combined with a chart called a nomogram to calculate the doses most likely to be therapeutic.

In either case, lithium levels should be monitored regularly. Side effects can occur at therapeutic levels or at those only slightly higher than desired. Blood tests that measure drug levels should be conducted frequently during acute attacks and about every 3 months during maintenance therapy.

Side Effects.

Minor side effects include:

• Trembling hands
• Nausea
• Increased urine output
• Blurred vision
• Some loss of coordination

More severe reactions, which occur at higher blood levels, include:

• Vomiting
• Convulsions
• Uncontrolled jerky movements in arms and legs
• Stupor
• Coma

Very high blood levels of lithium can be fatal.

If overdose occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on the severity:

• Patients are given fluids and drugs to increase excretion of lithium salts.
• Gastric lavage, a procedure that rinses the stomach, may be used to treat very recent overdoses.
• Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.

Long-Term Side Effects. Even for patients who do not experience a severe response, long-term use of lithium is not without problems. In one study, 16% of patients gained weight. Weight gain is one of the main reasons why some patients want to stop taking the drug. Other side effects include:

• An unpleasant taste in the mouth
• Hair loss
• Skin eruptions that can resemble acne and make psoriasis worse
• Low thyroid function
• An increased risk for diabetes
• A blunted sexual drive
• Dulled emotions and lack of mental clarity
• Memory loss
• Lack of motor coordination
• Reduced sensitivity to light.

In some cases, light sensitivity may slightly affect a person's ability to recognize colors. More seriously, it can cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Thiazide diuretics
• ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

• Antipsychotics
• Anticonvulsants
• Calcium-channel blockers

The risks associated with these drug interactions are very low, but caution is needed.

Other Factors that Affect Lithium Levels. In addition to drugs, other factors may affect lithium levels:

• Seasonal change -- lithium levels may be higher in summer.
• Menstrual cycle -- lithium levels may drop during the premenstrual phase.
• Weight loss
• Changes in salt intake
• Dehydration
• Diarrhea

Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.

Noncompliance. Noncompliance is common. One study of lithium users found that patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug.

Side effects are certainly one reason for noncompliance. Some patients regret the loss of their manic episodes and the exhilaration and creativity that sometimes accompany them. In one small study of artists with bipolar disorder, however, only 25% felt their work had declined, while another 25% found no change in their creative output, and 50% believed that lithium had improved their output.

Despite side effects and other concerns, this important drug saves lives. Doctors are confident that lithium, which has been in use for more than 50 years, can be taken safely, even for life, by most patients.

Valproate and Other Antiseizure Drugs

Antiseizure drugs, also called anti-epileptics or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. These drugs may be an alternative for patients (especially substance abusers) who do not tolerate or respond to lithium. They also may be used in combination with lithium, atypical antipsychotics, or other drugs.

Standard Antiseizure Drugs.

• Valproate (Depakote), also called valproic acid or divalproex, is now a first option for many bipolar disorder patients. Valproate also helps migraine headaches, a common problem among patients.
• Lamotrigine (Lamictal) is approved for maintenance treatment of adults with bipolar I disorder. It also appears to be better for treating bipolar depression than other mood stabilizers.
• Carbamazepine (Epitol, Tegretol) is a standard alternative antiseizure drug used for mood stabilizing. In 2004, the FDA approved an extended release form of carbamazepine (Equetro). Oxcarbazepine (Trileptal) is another drug that is similar to carbamazepine.

General Side Effects. The side effects given here are associated with valproate. Other antiseizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy and then subsiding. Valproate side effects include:

• Gastrointestinal problems such as nausea, vomiting, and heartburn
• Headaches
• Visual disturbances
• Ringing in the ear
• Hair loss
• Weight gain (a significant problem with valproate)
• Agitation
• Odd movements
• Menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
• Birth defects when taken by pregnant women
• Cognitive impairment and symptoms of Parkinson's disease

Very serious side effects are possible. Stevens-Johnson syndrome (SRS) is a rare but severe and potentially life-threatening, rash that can develop as a side effect of carbamazepine, lamotrigine, oxcarbazepine and other anticonvulsants. Because this is a very serious condition, these drugs are discontinued at the first sign of rash. Other serious side effects, also rare, may include:

• Liver damage
• Convulsions
• Coma
• Pancreatitis

Atypical Antipsychotics

Atypical antipsychotics are standard drugs for schizophrenia. They are now proving to be beneficial for bipolar disorder when used alone or in combination with the mood stabilizers that treat mania. These drugs include clozapine (Clozaril) (the first atypical antipsychotic), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), aripiprazole (Abilify) and ziprasidone (Geodon).

• Olanzapine was the first atypical antipsychotic approved for treatment of bipolar disorder. In 2000, the FDA approved it to treat bipolar mania and mixed states. In 2004, the drug became the first atypical antipsychotic approved for bipolar maintenance treatment.
• Symbyax, a drug that combines olanzapine and the antidepressant fluoxetine, was approved in 2003 for treatment of bipolar depression.
• Risperidone, ziprasidone, and ariprazole are approved for treatment of bipolar mania and mixed states. Quetiapine is approved for treatment of bipolar mania and bipolar depression, making it the only drug approved for treating both manic and depressive states.
• Clozapine has not yet been approved for treatment of bipolar disorder, but has shown promise in investigative studies. However, this drug has more significant side effects than other atypical antipsychotics. It poses a risk of white blood cell reduction (agranulocytosis) and has the highest risk of weight gain of all atypicals.

Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include the following:

• Nasal congestion or runny nose
• Drooling
• Dizziness
• Headache
• Drowsiness -- however, these drugs may also cause restlessness and insomnia.
• Constipation
• Rapid heart beat
• Difficulty urinating
• Skin rash
• Increased body temperature
• Confusion, short-term memory problems, disorientation, and impaired attention
• Weight gain -- risk is highest with clozapine and olanzapine.

Atypicals also have some rare but serious side effects:

• Diabetes. All atypical antipsychotics can increase the risk of elevated blood sugar (hyperglycemia) and diabetes. The risk is highest for clozapine and olanzapine. All patients treated with atypical antipsychotics should receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment.
• Seizures. There is a 5% risk per year with clozapine. Others pose less of a risk.
• Heat stroke. People who take atypicals have a higher risk of heat stroke.
• Extrapyramidal effects, which are lack of motor coordination and involuntary movements.
• The risk for cataracts increases. Existing glaucoma may get worse.
• Prolactin levels may be increased. Prolactin is a hormone that can cause fluid secretions from breasts in women or impotence in men. Women with increased prolactin levels have a higher risk for breast cancer.
• Heart problems, including arrhythmias, have been reported with initial usage of the drug. The risk for abnormal heart rhythms appears to be highest with clozapine and olanzapine, moderate with risperidone, and low with quetiapine.
• Agranulocytosis is a potentially life-threatening reduction in certain white blood cells. This complication occurs in about 1% of people taking clozapine, most often after 3 months of treatment, and peaks in the third month. This complication can be reversed if the drug is withdrawn at once. Older women are at higher risk.

Antidepressants

Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. A 2002 study suggested that they may be helpful for patients whose depression occurs after an episode-free period (rather than after a manic or hypomanic episode.) Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.

Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. (A newer "designer antidepressant," venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.) Side effects of SSRIs include:

• Nausea and gastrointestinal problems, which usually wear off over time
• Agitation, insomnia, mild tremor, and impulsivity
• Dry mouth, which can increase the risk for cavities and mouth sores
• Headache
• Sexual dysfunction

Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.

Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.

Calcium-Channel Blockers

Calcium-channel blockers are drugs commonly used for treating angina and high blood pressure. They also have nerve-protecting properties. Several studies indicate that at least one of these drugs -- verapamil (Calan, Isoptin, Verelan) -- has anti-manic and possibly mood-stabilizing effects. In a 2002 study, all patients with mania or hypomania reported at least a 50% improvement in their symptoms. In addition, 78% of patients with mixed states reported that mania improved and 39% of patients with depression and no mania or hypomania improved. Other calcium channel blockers, such as nimodipine (Nimotop), may help treat ultra-rapid cycling. Nimodipine has been shown to reduce hypomania and may work particularly well when added to carbamazepine.

These drugs do not cause mental dysfunction, sedation, or weight gain as do other bipolar drugs. They may be safer during pregnancy and breastfeeding. Their side effects can include fluid build-up in the feet, constipation, fatigue, impotence, gingivitis, flushing, and allergic symptoms. Overdose can cause a severe drop in blood pressure. Note: Grapefruit and Seville (sour) oranges boost the effects of calcium-channel blocking drugs. (Regular oranges do not appear to pose any problems.)

Other Treatments

Electroconvulsive Therapy

Electroconvulsive therapy (ECT is a non-drug treatment for bipolar disease and other mental disorders, such as severe depression. It is commonly called shock therapy. ECT has received bad press since it was introduced in the 1930s. But, over the years it has been refined, and is now considered a very safe treatment.

Research suggests ECT may be particularly beneficial for:

• Patients who need immediate stabilization of their condition and who cannot wait for medications to work
• Most patients with mania -- especially elderly patients with severe mania
• Patients who suffer suicidal thoughts and guilt during the depressive phase
• Pregnant patients
• Patients who cannot tolerate drug treatments
• Patients with certain types of heart problems
• Young patients

In a review of studies, about 80% of ECT-treated patients experienced improvement, and for some, it is the only treatment that works.

The Procedure. ECT is performed on an outpatient basis and does not require hospitalization. In general, the ECT procedure is performed as follows:

• A muscle relaxant and short-acting anesthetic are given to the patient.
• A small amount of electricity is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
• The response to ECT is usually very fast, and the patient often needs less medication afterward.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Taking the drug naloxone immediately before ECT may help reduce its effects on concentration and some (but not all) forms of memory impairment. Concerns about permanent memory loss appear to be unfounded. One study that used brain scans before and after ECT found no evidence of cell damage. In another small study of teenagers who had undergone ECT for severe mood disorders, only 1 in 10 reported memory impairment 3.5 years after treatment.

Biologic Effects of ECT on Bipolar Disorder. The precise way that ECT benefits patients with bipolar disorder is not clear. ECT may help by:

• Causing changes in the brain's physiology. For example, ECT may increase the permeability of the blood-brain barrier, produce an antiseizure effect (similar to the effects of antiseizure drugs used as mood stabilizers), and reduce blood flow in parts of the brain associated with improved mood.
• Causing various hormonal changes, particularly with thyroid-related hormones
• Balancing dopamine levels. This brain chemical plays an important role in bipolar disorder as well as other conditions for which ECT is sometimes recommended, including delusional depression.
• Stimulating growth of neurons in the hippocampus (the area in the brain responsible for memory)

Some studies are finding that maintenance electroconvulsive therapy (ECT) may be helpful for patients who do not respond to medications. In one study of patients with bipolar disorder, those who had intractable recurrent episodes received monthly ECT treatments for more than a year and a half. Without ECT, those patients spent an average of almost half a year in the hospital, suffering at least three episodes annually. After ECT, all the rapid cyclers achieved full or partial remission.

Experimental Procedures

Magnetic Therapy. Repeated transcranial magnetic stimulation (rTMS) is also being studied for unipolar and bipolar depression. Unlike ECT, this procedure does not appear to cause seizures, memory lapses, or impaired thinking. The only common side effect is a mild headache.

Therapy and Lifestyle Changes

Classic psychotherapy does not help most patients with bipolar disorder. Nevertheless, many newer approaches are proving to be very useful. Trained mental health professionals can:

• Educate patients about bipolar disorder and its treatments
• Help them comply with drug regimens
• Monitor the patient's on-going status
• Intervene early in manic and depressive episodes to reduce the severity of the attack

In addition, trained professionals can help patients:

• Adjust to the reality of the illness and understand the negative consequences of mania -- particularly important for patients who consider their mania to be positive, creative, and exhilarating
• Cope with feelings of guilt and remorse that occur after manic episodes
• Deal with feelings of imperfection and despair

Cognitive-Behavioral Therapy

Therapists trained in cognitive-behavioral therapy (CBT) may be particularly helpful for many patients. CBT is a structured, conscious method that aims to help a patient recognize negative thoughts and behavioral patterns and to change them. CBT is known to be helpful for other mood disorders, including depression and anxiety, and some studies suggest that it benefits bipolar disorder patients as well. For example, in a 2003 study, patients who were given mood stabilizers and underwent a CBT program that was specifically designed to prevent relapse experienced fewer and shorter episodes and improved social functioning compared to those on mood stabilizers alone.

Using Cognitive-Behavioral Therapy for Bipolar Disorder. Typical goals of CBT for bipolar disorder patients include learning how to:

• Recognize manic episodes before they become full-blown and change behaviors during an episode
• Cope with depression by developing behaviors and thoughts that may help offset the negative mood

Monitoring and Grading Mood. One useful technique is a method that helps the patient predict or recognize an impending episode. This is done using a graph and diary that records and grades the effect of the patient's mental state on energy and physical activity.

There are a number of charts for doing this. With one method, the patient makes a time line across the page and a vertical line on the left side of the time line with a range from -5 to +5:

• -5 to -1 indicate the depressive phase. Minus five is the most severe depressive state and requires hospitalization. At this score, the patient's psychomotor responses are almost entirely negative. The patient is unable to function, has no appetite, and can barely get out of bed. As the scale moves up to zero, the depressive state lessens, so that -1 indicates a subdued mood with slightly less energy than normal.
• Zero is normal.
• +1 to +5 indicate the manic phase. For example, +1 indicates a slightly more active and energetic state than normal. Plus five is the most severe manic state, where the patient is incapable of slowing down, experiences impaired thinking and judgment, and sleeps at least 2 hours less than normal.

To fill out the graph, the patient takes the following steps:

• Using a diary, the patient describes each day, the mood, and its effect on physical activities.
• Using this information, the patient makes a mark on the scale that roughly reflects each day's mood and its effect on function. The patient then connects the mark with that of the previous day's state.
• The patient also describes any significant emotional or physical events, menstruation, medications, and dosages taken, or any factor that may be relevant in influencing mood or activities.
• After several months, the therapist and patient may be able to detect a pattern and possibly identify triggers of bipolar disorder episodes.
• Such information helps the patients to make adjustments that might reduce the severity of mood swings. For example, if a predictor for either manic or depressive episodes is insomnia, the doctor might use sleep-inducing methods or medications that might reduce the severity of the emerging mania.

Family Therapy

It is very important that partners, family members, or both be involved in therapy. CBT can help them learn how to accept the condition, the need for medications, and how to protect themselves and the patient financially during manic episodes. In fact, one study indicated that when a spouse of a patient learned ways of coping with the illness, the partner's chances of sticking to a prescribed treatment improved.

Supporting the Patient. Recommendations for supporting the patient include:

• Create a treatment contract as a first step. In this contract, the patient and family agree to specific steps for maintaining emotional stability. If such measures fail, all parties agree on further actions to be taken during an acute episode, including requests for hospitalization.
• Be supportive. Unlike relatives of patients with alcoholism who may be encouraged to get tough, relatives of patients with bipolar disorder must be strongly supportive because of the high risk for suicide with this disorder. Simply listening attentively and being empathic can help.
• Get the patient to comply with treatment, even if it means threatening a hospitalization if the patient fails to comply.
• Have ready a hotline number or the telephone number of a psychiatrist authorized to commit the patient. The doctor should be willing to facilitate commitment if a patient becomes violent or the family is on the verge of collapse.
• Don't feel guilty and don't make the patient feel guilty. Bipolar disorder results from an imbalance of chemicals in the brain and not from anyone's fault.

Support for the Family. Unfortunately, actions that support a bipolar disorder patient may not be intuitive, and they take their toll. Loved ones must also care for themselves or they may also follow a path to severe depression. They should to boost energy and reduce stress through:

• Exercise
• Meditation
• Relaxation techniques
• Holidays away from the patient
• Involvement in hobbies
• Involvement in support groups, Internet resources with chat rooms, and message boards for bipolar disorder caregivers

Interpersonal and Social Rhythm Therapy

Interpersonal problems (such as family disputes) and disruptions in daily routines or social rhythms (such as loss of sleep or changes in meal times) may make people with bipolar disorder more susceptible to new episodes of their illness. A form of psychosocial treatment called interpersonal and social rhythm therapy (IPSRT) focuses on maintaining a regular schedule of daily activities to reduce these potential triggers and improve emotional stability. Patients also learn how to avoid problems with personal relationships. Preliminary evidence suggests that IPSRT combined with drug therapy works better than medication alone. A 2-year study of patients with bipolar 1 disorder indicated that IPSRT may help prevent new manic episodes.

Lifestyle Factors

Exercise. Exercise is an important part of treatment, particularly in helping manage weight gain. It also helps increase feelings of well-being.

Sleep Management. Good sleep hygiene is particularly important for patients. One study reported that techniques used to enforce healthy sleep helped reduce mood cycling.

Diet. A healthy diet low in saturated foods and rich in whole grains, fresh fruits, and vegetables is important for anyone. People with bipolar disorder should be sure to maintain a regular healthy diet. They may need to restrict calories if they are on medications that increase weight.

Some research indicates that consumption of omega-3 polyunsaturated fatty acids found in oily fish (such as mackerel, sardines, salmon, and bluefish) may help reduce the symptoms of a variety of mental illnesses, including bipolar disorder. Researchers are investigating the effects of eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) supplements for patients who have not responded to other treatments. A preliminary 2002 study found that they may benefit patients with depressive symptoms more than those with mania.

Resources

• www.nimh.nih.gov -- National Institute of Mental Health
• www.bpkids.org -- Child & Adolescent Bipolar Foundation
• www.dbsalliance.org -- Depression and Bipolar Support Alliance
• www.nami.org -- National Alliance on Mental Illness
• www.nmha.org -- Mental Health America
• www.aabt.org -- Association for Behavioral and Cognitive Therapies
• www.psych.org -- The American Psychiatric Association
• www.aacap.org -- American Academy of Child and Adolescent Psychiatry

References

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Bauer MS, McBride L, Williford WO, Glick H, Kinosian B, Altshuler L, et al. Collaborative care for bipolar disorder: Part II. Impact on clinical outcome, function, and costs. Psychiatr Serv. 2006 Jul;57(7):937-45.

Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta L, et al. Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Feb;63(2):175-83.

Johannessen L, Strudsholm U, Foldager L, Munk-Jorgensen P. Increased risk of hypertension in patients with bipolar disorder and patients with anxiety compared to background population and patients with schizophrenia. J Affect Disord. 2006 Oct;95(1-3):13-7.

Kalsi G, McQuillin A, Degn B, Lundorf MD, Bass NJ, Lawrence J, et al. Identification of the Slynar gene (AY070435) and related brain expressed sequences as a candidate gene for susceptibility to affective disorders through allelic and haplotypic association with bipolar disorder on chromosome 12q24. Am J Psychiatry. 2006 Oct;163(10):1767-76.

Kessler RC, Akiskal HS, Ames M, Birnbaum H, Greenberg P, A RM, et al. Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers. Am J Psychiatry. 2006 Sep;163(9):1561-8.

Olfson M, Blanco C, Liu L, Moreno C, Laje G. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. Arch Gen Psychiatry. 2006 Jun;63(6):679-85.

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