Bipolar disorder
Highlights
Drug Approval
In 2007, the FDA approved risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17. Risperidone (an atypical antipsychotic) and lithium (a mood stabilizer) are the two drugs currently approved for treating pediatric patients with bipolar disorder.
Drug Warnings
- Olanzapine (Zyprexa, Symbex) causes a greater risk for high blood sugar than other atypical antipsychotics, according to updated information added to the drugs warning label. Olanzapine also causes weight gain and can increase the risk for unhealthy cholesterol levels.
- All atypical antipsychotics increase the risk for diabetes. Patients who take these drugs should receive regular screenings for changes in blood sugar levels. Patients should also have their cholesterol levels monitored.
Bipolar Disorder in Children and Adolescents
- Diagnoses of bipolar disorder in children have increased 40-fold in the past decade, according to an analysis in the Archives of General Psychiatry. There is debate whether bipolar disorder in children was under-diagnosed in the past or is being over-diagnosed now.
- Bipolar symptoms in children differ from those of adults, with some symptoms overlapping with behavioral and conduct disorders. New guidelines from the American Academy of Child and Adolescent Psychiatry (AACP) caution that a diagnosis of bipolar disorder must be carefully made, especially considering the risks associated with drug therapy. The AACP also advises that there are currently no established criteria for diagnosing bipolar disorder in preschoolers.
Bipolar Depression
- The antidepressants bupropion (Wellbutin) and paroxetine (Paxil) do not increase the risk for mania, but neither do they help ease depression any more than mood stabilizers, suggests a 2007 study in the New England Journal of Medicine.
- Intensive psychotherapy in combination with medication can help improve depression outcomes, indicates a 2007 study in the Archives of General Psychiatry.
Introduction
Bipolar disorder, or manic-depressive illness, is characterized by moods that swing between two opposite poles:
- Periods of mania with exaggerated euphoria, irritability, or both
- Episodes of depression
Although chemical imbalances in the brain are a key component of bipolar disorder, it is a complex condition that involves genetic, environmental, and other factors.
Bipolar Disorder 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, that lasts for at least 7 days. In 60 - 70% of cases, manic episodes precede or follow depressive episodes in a regular pattern. Episodes are more acute and severe than in the other two categories.
Without treatment, patients average four episodes of dysregulated mood each year. With mania, either euphoria or irritability may mark the phase. In addition, there are significant negative effects (such as sexual recklessness, excessive and impulsive shopping, and sudden traveling) on a patient's social life, performance at work, or both. Untreated mania lasts at least a week, and it can last for months. Typically, depressive episodes tend to last 6 - 12 months, if left untreated.
Bipolar Disorder II and Hypomania. Bipolar disorder II is characterized by episodes of predominantly depressive symptoms, with occasional episodes of hypomania, which last for at least 4 days. Hypomania is similar to mania, but the symptoms (typically euphoria) are less severe and do not last as long.
Patients do not experience manic or mixed episodes, and most return to fully functional levels between episodes. However, bipolar II patients have a more chronic course, significantly more depressive episodes, and shorter periods of being well between episodes than patients with type I have. It is highly associated with the risk for suicide.
Cyclothymic Disorder. While cyclothymic disorder is not as severe as either bipolar disorder II or I, the condition is more chronic. Hypomanic symptoms tend toward irritability as compared to the more euphoric symptoms of bipolar II. (One report, in fact, referred to these patients as having "darker" natures, while bipolar II patients were "sunnier.")
The disorder lasts at least 2 years, with single episodes persisting for more than 2 months. Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people or it may continue as a low-grade chronic condition.
Symptoms of Bipolar Disorder
Symptoms of the Depression Phase. The symptoms of depression experienced in bipolar disorder are almost identical to those of major depression, the primary form of unipolar depressive disorder. They include:
- Sad mood
- Fatigue or loss of energy
- Sleep problems such as insomnia, excessive sleeping, or shallow sleep with frequent awakenings
- Appetite changes
- Diminished ability to concentrate or to make decisions
- Agitation or markedly sedentary behavior
- Feelings of guilt, pessimism, helplessness, or low self-esteem
- Loss of interest or pleasure in life
- Thoughts of, or attempts at, suicide
Distinguishing Between Unipolar and Bipolar Depression. It is often difficult to differentiate between unipolar and bipolar depression, particularly in patients with bipolar II disorder. They may differ in the following ways:
- Bipolar depression typically lasts 2 - 3 months -- not as long as in major depression (although left untreated some bipolar disorder episodes can last 6 - 12 months or longer).
- People with unipolar depression can still experience a variety of other moods, but none meet the criteria for a manic state.
- Depressive symptoms in those with bipolar disorder tend to vary. For example, some patients experience increased sleep, gain weight, and feel a heaviness and slowness in their bodies. Other patients with bipolar depression experience impaired sleep, but unlike patients with unipolar depression, they do not feel sleepy the next day.
- Bipolar depressive episodes tend to develop more gradually than do those caused by major depression.
Symptoms of the Acute Manic Phase. The acute pure manic phase is always characterized by mood elevation, presented in the following ways:
- Exaggerated euphoria (a feeling of great happiness or well-being)
- Irritability
- Both euphoria and irritability
The episode lasts for at least few days but, in some cases, the episode may last weeks or even months and may be severe enough to require hospitalization.
Other symptoms must also be present to make a diagnosis. Some mental health professionals use the mnemonic device DIGFAST to identify them. In general, for a diagnosis of mania, a patient must have experienced either euphoria with three DIGFAST symptoms or irritability with four of these symptoms:
- D. Distractibility. This is the most common symptom, and it is usually characterized by the inability to pay attention to any activity for very long.
- I. Insomnia in mania typically means having high energy and requiring less sleep. (This differs from insomnia in depression, in which the patient has low energy plus an inability to sleep.)
- G. Grandiosity. Patients with this symptom have an inflated sense of themselves, which, in severe cases, can be delusional. Close to 60% of all manic patients experience feelings of being all-powerful. Sometimes they feel that they are godlike or have celebrity status.
- F. Flight of ideas. Thoughts literally race.
- A. Activity. The patient may show an increase in intensity in goal-directed activities, which are related to social behavior, sexual activity, work or school.
- S. Speech. The patient may talk excessively.
- T. Thoughtlessness. Excessive involvement in high-risk activities is present (such as unrestrained shopping, promiscuity). Mood disturbance may be severe enough to damage one's job or social functioning or one's relationships with others. Some patients require hospitalization to prevent harm to others or to themselves.
Some patients with bipolar I may experience psychotic symptoms, including thought disorders, hallucinations, and catatonia (a state in which the patient goes into a stupor for long periods, which may give way to short periods of extreme excitement).
Hypomania. With hypomania the symptoms of mania are milder and of shorter duration (but they last at least 4 days). They do not affect social or work life as dramatically.
Mixed Mania State Symptoms. Mixed mania (also called mixed episodes or dysphoric mania) are manic episodes that also have a depressive component. In such a state, mania is present to a significant degree, but depression is present most of the day and nearly every day. Such mixed symptoms occur for at least a week.
Depressive Mixed State Symptoms. Depressive mixed state is characterized by major depression as the primary emotional state with manic features (such as irritability, distractibility, and racing thoughts). Such patients may receive an inaccurate diagnosis of unipolar depression.
Risk Factors
Between 1 - 2 million Americans may suffer from bipolar disorder. Researchers estimate that about 1% of Americans experience bipolar disorder during the course of their lifetime, but some studies indicate that prevalence may be as high as 4%. There is differing opinion on how to diagnose and categorize bipolar symptoms, which affects these estimates. The majority of people with bipolar disorder also have other psychiatric disorders, particularly anxiety and substance abuse.
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.
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. 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
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 experience mixed mania, or a mixed state, in which both mania and depression coexist for at least 7 days.
Rapid Cycling. About 15% of patients with the disorder have a temporary, complicated phase known as rapid cycling. With this phase the manic and depressive episodes alternate at least four times a year and, in severe cases, can even progress to several cycles a day. Rapid cycling tends to occur more often in women and in those with bipolar II. Typically, rapid cycling starts in the depressive phase, and frequent and severe episodes of depression may be the hallmark of this event. This phase is difficult to treat, particularly since antidepressants can trigger the switch to mania and set up a cyclical pattern.
Differences Between Children and Adults. Research suggests that symptoms of bipolar disorder in children and adolescents differ from those of adults. While adults with bipolar disorder usually have distinct and persistent periods of mania and depression, children with bipolar disorder fluctuate rapidly in their mood and behavior. Mania in children is characterized by irritability and belligerence whereas adults tend to experience euphoria. Children with bipolar depression are frequently angry and restless, and may have additional mood and behavioral disorders such as anxiety, attention deficit hyperactivity disorder, conduct disorder, and substance abuse problems.
Medical evidence has shown that patients with bipolar disorder have higher death rates from suicide, heart problems, and death from all causes than those in the general population. Patients who get treatment, however, experience great improvement in survival rates, including deaths from suicide and heart disease.
Age
Bipolar disorder usually first occurs between the ages of 15 - 30 years, with an average age of onset at 25 years. However, bipolar disorder can affect people of all ages, including children. Bipolar disorder that occurs late in life often accompanies medical and neurological problems (particularly cerebrovascular disease, such as stroke). It is less likely to be associated with a family history of the disorder than earlier-onset bipolar disorder.
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. The risk for both diagnoses is highest in white males. Symptoms are also more severe in people with both conditions. Some researchers believe that many of these disorders may actually be variations of a single disease.
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, and the risk for suicide is high. They have a higher risk for mixed mania, multiple and frequent cycles, and a long duration of illness without well periods.
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 disorders 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. Many patients with bipolar disorder are overweight, with about 25% meeting the criteria for obesity. Being overweight is a significant risk factor for diabetes and so it may be the common factor in both diseases. Drugs used to treat bipolar can also cause weight gain and diabetes. Common genetic factors in diabetes and bipolar disorder may cause a rare disorder called Wolfram syndrome and other problems with carbohydrate metabolism.
High Blood Pressure. Patients with bipolar disorder may be at a higher risk for high blood pressure (hypertension) than patients without the disorder. The high prevalence of hypertension among patients with bipolar disorder may also account for their greater risk for illness and death from heart-related conditions.
Migraine Headaches. Migraines are common in patients with a number of mental illnesses, but they are particularly common among patients with bipolar II disorder. Patients with bipolar II suffer from migraine more frequently than patients with bipolar I, suggesting that different biologic factors may be involved with each bipolar form.
Hypothyroidism. Hypothyroidism (low thyroid levels) is a common side effect of lithium, the standard treatment for bipolar. However, evidence also suggests that patients, particularly women, may be at higher risk for low thyroid levels regardless of which medications they use. Hypothyroidism may, in fact, be a risk factor for bipolar disorder in some patients.
Diagnosis
Bipolar disorder is more common than previously thought, but this illness, particularly bipolar disorder II, is still poorly recognized in the family-practice setting. It is estimated that only a third of affected people are accurately diagnosed.
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 and may not have a manic episode until they have experienced three or more depressive episodes. In such cases, the condition is often diagnosed as major depression. An accurate diagnosis is important because patients with bipolar disorder who are inappropriately medicated solely with antidepressants have a higher incidence of rehospitalization than do other bipolar disorder patients.
Bipolar disorder should be suspected in patients who have been treated for depression and who had a fast and good response, followed by the return of depression and failure to respond to other antidepressant treatment.
A family history of manic-depressive illness may make a doctor suspicious, but a diagnosis of bipolar disorder cannot be established until a manic or hypomanic episode has occurred. Patients with bipolar II disorder and those with depressive mixed state are most likely to be misdiagnosed with depression.
Attention Deficit Hyperactive Disorder (ADHD). Children or adolescents with bipolar disorder may be inappropriately diagnosed with attention-deficit hyperactivity disorder. ADHD and bipolar disorder often cause inattention and distractibility, and the two disorders may be difficult to distinguish, particularly in children. In some cases, ADHD in children or adolescents can even be a marker for an emerging bipolar disorder. The primary distinction between bipolar disorder and ADHD is the presence of a manic or hypomanic episode, which occurs in patients with bipolar disorder but not those with ADHD.
Schizophrenia. Severe manic episodes that include delusions and hallucinations may be easily confused with schizophrenia. (African-American men are more likely to be diagnosed with schizophrenia than with bipolar disorder.) The key factors that distinguish bipolar disorder from schizophrenia include:
- The presence of one or more manic or hypomanic episodes in bipolar disorder, but not in schizophrenia
- A flat emotional expression, with no variability in the voice among people with schizophrenia
- People with bipolar disorder are typically very expressive
Substance Abuse. Up to 60% of patients with bipolar disorder abuse alcohol and drugs at some point during their illness. Both diagnosis and treatment are difficult in such cases, since substance abuse is often a method of self-treatment, and withdrawal can produce symptoms of mania or severe depression. The effects of cocaine in a heavy user can also produce abnormal mood swings that closely resemble those of bipolar disorder.
Other Causes of Mood Swings. Other conditions that can cause mood swings include:
- Thyroid disorders
- Adrenal disorders (Addison's disease or Cushing syndrome)
- Vitamin B12 deficiency
- Neurologic disorders such as Huntington's disease, epilepsy, brain tumors, encephalitis, or multiple sclerosis
- Medications, including corticosteroids and certain drugs used to treat anxiety and Parkinson's disease
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 evaluated in clinical trials for detecting abnormalities in the brain. The results of these tests may eventually help identify bipolar disorder and test the effectiveness of various treatments. However, imaging tests do not currently play a role in diagnosing bipolar disorder.
Diagnosis in Children
The number of children diagnosed with bipolar disorder has increased dramatically during the past decade. Psychiatrists debate whether bipolar disorder was formerly under-diagnosed in children or whether it is being over-diagnosed now. Part of the controversy concerns the diagnostic criteria used for children and adolescents. Some bipolar symptoms, such as irritable mania, share characteristics with common childhood anger outbursts or behavioral disorders such as conduct disorder and attention deficit hyperactivity disorder. In addition, many children with bipolar disorder also have behavioral and developmental disorders. These overlapping conditions can complicate diagnosis.
The American Academy of Child and Adolescent Psychiatry (AACP) recommends that doctors use specific screening questions to diagnose bipolar disorder. These questions are designed to evaluate periods of mood changes associated with sleep disorders and restlessness. Doctors should also ask about family histories of mood disorders. The AACP cautions that the validity of diagnosing bipolar disorder in children younger than 6 years old has not been established.
Bipolar disorder is treated with powerful psychiatric drugs that can cause serious side effects. It is very important to make sure that a childs symptoms are due to bipolar disorder, rather than emotional or behavioral issues, before prescribing these medications.
Treatment
Bipolar disorder is a recurrent disease that can be unpredictable. The major goals of treatment are to:
- Treat and reduce the severity of acute episodes of mania or depression when they occur
- Reduce the frequency of episodes
- Avoid cycling from one phase to another
- Help the patient function as best as possible between episodes
The doctor will first try to determine what may have triggered the attack and identify any accompanying medical or emotional problems that might interfere with or complicate treatment.
Some experts think that the best way to treat bipolar disorder is through a disease management model, similar to those used for treating diabetes and asthma. In this collaborative care model, patients are treated by a multi-disciplinary team of psychiatrists and nurses. The nurses provide patient education on medication side effects, early warning signs of symptoms, and coping skills. In several 2006 studies, patients who received this treatment model reported fewer symptoms, more productive time at work, better relationships with family members, and general improvement in quality of life.
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) carbamazepine (Tegretol, Carbatrol, Equetro), oxcarbazepine (Trileptal), and lamotrigine (Lamictal) are the most established antiseizure drugs. Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
- Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Clozapine (Clozaril) was the first of these drugs, but it has not yet been approved for treatment of bipolar disorder. The newer atypical antipsychotics include olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and ariprazole (Abilify).
Such drugs may be used in combination with each other. Additional drugs, such as conventional antipsychotics, antidepressants, antianxiety drugs, or experimental drugs are used as necessary.
Electroconvulsive Therapy. Electroconvulsive therapy is a very effective treatment that may be administered in certain patients for acute episodes or for maintenance.
Non-Medical Treatments. In addition to medical treatments, psychotherapy and sleep management are also parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.
The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), an ongoing trial supported by the National Institute of Mental Health, is the largest treatment study ever conducted for bipolar disorder. With plans to enroll approximately 5,000 patients, STEP-BD aims to evaluate all the best-practice treatment options used for bipolar disorder, including mood-stabilizing medications, antidepressants, and atypical antipsychotics. It will also evaluate psychosocial interventions, including cognitive behavioral therapy, family-focused therapy, interpersonal and social rhythm therapy, and psychoeducation. Results of STEP-BD may clarify the best treatments for bipolar disorder.
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:
- Older antipsychotic drugs (also called typical antipsychotics), such as haloperidol (Haldol), may be used for acute mania. They can cause severe side effects, however, particularly extrapyramidal effects, which disrupt motor control. They are not generally used on a long-term basis for treating bipolar disorder.
- Benzodiazepines, such as clonazepam (Klonopin) or lorazepam (Ativan), are anti-anxiety drugs that may be particularly beneficial if the patient is experiencing severe mania.
- Electroconvulsive therapy. This treatment helps patients who do not respond to medication and may even be life-saving in elderly patients with severe late-onset mania.
Step 4. Terminate Some Drug Treatments. Drugs may be stopped under the following circumstances:
- When side effects are intolerable
- When the patient does not respond to the maximum dose
- When the patient improves and recovery is sustained
In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.
Step 5. Continuation of Mood Stabilizers. Mood stabilizers are typically continued for about 8 weeks, unless the patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.
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 very difficult and patients who do not respond to mood stabilizers may endure prolonged depressive episodes up to 2 - 3 months.
Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.
If improvement does not occur within 2 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).
Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to switch to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.
An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the Food and Drug Administration (FDA) approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax was the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.
Other Treatments. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches.
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, particularly SSRIs, may prompt rapid cycling and should be tapered off.
- Lithium or valproate is a first-line treatment for rapid cycling.
- Lamotrigine is an alternative treatment for rapid cycling.
- Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
- One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
- Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
- Electroconvulsive therapy can be useful in emergency situations.
In addition, other measures should be taken:
- Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
- Patients should avoid exposure to bright light.
- All efforts should be made to help the patient sleep normally.
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 due to an increased suicide risk.
- Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
- For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.
Guidelines for the Treatment of Pregnant Patients with Bipolar Disorder
Information on clinical care of pregnant women with bipolar disorder remains very limited. In fact, in one survey, almost half of women with bipolar disorder were discouraged by their doctors from becoming pregnant. Nevertheless, after careful counseling about medications, possibilities for relapse, and disease severity, nearly two-thirds of them decided to attempt pregnancy.
Risks for Bipolar Episodes. Some studies suggest the following risks for bipolar episodes during and after pregnancy:
- In women who discontinue lithium during pregnancy, the chance for recurrence of bipolar disorder is the same as in non-pregnant women, which is over 50%.
- Pregnant women with bipolar disorder are at particularly high-risk for recurrence in the period after childbirth. In one study, symptoms recurred in 74% of women after delivery, and another 20% were hospitalized within 90 days after giving birth. The risk for depressive or mixed states is particularly high.
Drugs for Bipolar and Pregnancy. It is not ethical to test drugs during pregnancy, so all known effects of bipolar drugs are reported anecdotally. It is well-known, however, that most mood stabilizers used for bipolar disorder carry a high risk for the fetus, particularly if they are taken during the first trimester. Taking mood stabilizers at the time of delivery may help reduce the risk of manic episodes occurring after the baby is born. However, caution is still advised. Reported effects of drugs taken during pregnancy include:
- Lithium can pass through the placenta and affect the fetus. When possible, patients should avoid taking lithium during pregnancy, especially during the first 3 months. Studies report that lithium use during the first trimester may cause heart defects and thyroid problems in the baby. If taken immediately before childbirth, lithium can also cause muscle weakness and drowsiness in newborn infants. Women who must take lithium during pregnancy should take the lowest possible dosage and stop the drug 1 - 2 days before delivery. Mothers who are taking lithium should not nurse their babies, since lithium is concentrated in breast milk.
- The antiseizure drugs valproate and carbamazepine both greatly increase the risk for physical malformations, developmental delay, and spina bifida in babies. They appear to have minimal effect on breastfeeding, however. Lamotrigine can cause cleft lip and palate birth defects if taken during the first trimester.
- Small studies have suggested that the atypical antipsychotic olanzapine does not increase the risk for birth defects. However, it does pose a great risk for excess weight gain that could be unhealthy during pregnancy. Less is known about the effects of other atypical antipsychotics during pregnancy.
Electroconvulsive Therapy (ECT). In spite of its bad press, ECT appears to be very beneficial for women with bipolar disorder who become pregnant. The patient should discuss this option with her doctor.
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.
Until recently, lithium was the only drug approved for treating bipolar disorder in children (age 12 years and older). In 2007, the FDA approved the atypical antipsychotic risperidone (Risperdal) for short-term treatment of manic or mixed episodes of bipolar I disorder in children ages 10 - 17.
Lithium is generally used as the first-line treatment, with valproate and risperidone (or other atypical antipsychotics) as alternatives. If treatment with a single drug does not work, a combination of drugs may be used.
Lithium and valproate are the drugs most studied in children and adolescents. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination, weight gain (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate). Side effects of risperidone may include drowsiness, fatigue, increased appetite, nausea, dizziness, dry mouth, tremor, and rash.
Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.
Psychotherapy is also an important addition to drug treatment. Therapy that includes the entire family is important. Electroconvulsive therapy (ECT) may benefit adolescents with bipolar I disorder who suffer severe episodes of mania or depression and who have not been helped by medication.
Medications
Lithium
Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) is one of the standard mood stabilizing drugs for bipolar disorder. Lithium is extremely helpful for most patients and it significantly reduces the rate of hospitalizations in bipolar disorder. Some studies report the following advantages of lithium:
- Lithium is effective in 60 - 80% of all hypomanic and manic episodes. (Valproate may be better in patients with multiple manic episodes, mixed episodes, and rapid cycling.)
- It helps to prevent relapses.
- It helps psychosocial functioning.
- It may help reduce the risk for suicide regardless of its effects on stabilizing mood.
- It works well for most patients even if they have discontinued taking it and wish to restart treatment.
Administration of Lithium. Lithium may take weeks to become totally effective, so patients should not expect an immediate response during an acute episode. Doctors may take different approaches to administering the drug:
- Some doctors initially administer lithium in two low doses and gradually increase the dosage over time until an effective (therapeutic) level is achieved.
- Another approach is to administer a higher dose initially and measure blood levels of the drug after 24 hours. The doctor uses this information combined with a chart called a nomogram to calculate the doses most likely to be therapeutic.
In addition to drugs, several factors may affect lithium levels:
- Seasonal change -- lithium levels may be higher in summer.
- Menstrual cycle -- lithium levels may drop during the premenstrual phase.
- Weight loss
- Changes in salt intake
- Dehydration
- Diarrhea
Lithium levels should be monitored regularly. Side effects can occur at therapeutic levels or at those only slightly higher than desired. Blood tests that measure drug levels should be conducted frequently during acute attacks and about every 3 months during maintenance therapy.
Lithium Toxicity. Evidence of moderate toxicity include:
- Trembling hands
- Nausea
- Increased urine output
- Blurred vision
- Some loss of coordination
Severe reactions occurring at higher blood levels, include:
- Vomiting
- Convulsions
- Uncontrolled jerky movements in arms and legs
- Stupor
- Coma
Very high blood levels of lithium can be fatal. If overdose occurs, drugs should be stopped immediately and one or more of the following steps taken, depending on the severity:
- Patients are given fluids and drugs to increase excretion of lithium salts.
- Gastric lavage, a procedure that rinses the stomach, may be used to treat very recent overdoses.
- Hemodialysis, a procedure that filters lithium out of the blood, may also be performed in severe cases.
Side Effects. Even for patients who do not experience a severe response, long-term use of lithium is not without problems. Weight gain is one of the main reasons why some patients want to stop taking the drug. Other side effects include:
- An unpleasant taste in the mouth
- Hair loss
- Skin eruptions that can resemble acne and make psoriasis worse
- Low thyroid function
- An increased risk for diabetes
- A blunted sexual drive
- Dulled emotions and lack of mental clarity
- Memory loss
- Lack of motor coordination
- Increased sensitivity to light
In some cases, light sensitivity may slightly affect a person's ability to recognize colors. More seriously, it can cause problems with night driving. This effect occurs regardless of how long a person has been on the drug. Experts recommend that patients wear sunglasses outside and avoid extensive exposure to bright light.
Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Thiazide diuretics
- ACE inhibitors
There have been reports of interactions between lithium and certain drugs commonly used in combination, including:
- Antipsychotics
- Anticonvulsants
- Calcium-channel blockers
The risks associated with these drug interactions are very low, but caution is needed.
Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.
Noncompliance. Noncompliance is common. One study of lithium users found that patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug.
Side effects are certainly one reason for noncompliance. Some patients regret the loss of their manic episodes and the exhilaration and creativity that sometimes accompany them. In one small study of artists with bipolar disorder, however, only 25% felt their work had declined, while another 25% found no change in their creative output, and 50% believed that lithium had improved their output.
Despite side effects and other concerns, this important drug saves lives. Doctors are confident that lithium, which has been in use for more than 50 years, can be taken safely, even for life, by most patients.
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. It works well for many patients with mania, rapid-cycling, and mixed states, as well as for patients who are substance abusers. Valproate also helps migraine headaches, a common problem among patients.
- Lamotrigine (Lamictal) is approved for maintenance treatment of adults with bipolar I disorder. It appears to be particularly helpful for patients with rapid cycling and bipolar II disorder, in whom depression remains problematic after taking other mood stabilizers.
- Carbamazepine (Epitol, Tegretol), a standard alternative antiseizure drug used for mood stabilizing, is usually the second anti-seizure medication of choice. In 2004, the FDA approved an extended release form of carbamazepine (Equetro). Another drug, oxcarbazepine (Trileptal), is similar to carbamazepine.
- Other anti-seizure drugs used or investigated for bipolar include gabapentin (Neurontin), zonisamide (Zonegran) and topiramate (Topamax). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
General Side Effects. The side effects given here are associated with valproate. Other antiseizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy and then subsiding. Valproate side effects include:
- Gastrointestinal problems such as nausea, vomiting, and heartburn
- Headaches
- Visual disturbances
- Ringing in the ear
- Hair loss
- Weight gain (a significant problem with valproate)
- Agitation
- Odd movements
- Menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)
- Birth defects when taken by pregnant women
- Cognitive impairment and symptoms of Parkinson's disease
Very serious side effects are possible. Stevens-Johnson syndrome (SJS) is a rare but severe and potentially life-threatening, rash that can develop as a side effect of carbamazepine, lamotrigine, oxcarbazepine and other anticonvulsants. Because this is a very serious condition, these drugs are discontinued at the first sign of rash. The risk of serious skin reactions is 10 times higher for patients of Asian ancestry than Caucasians. The FDA recommends that people of Asian ancestry get a genetic test before starting carbamazepine to determine if they are at risk for this side effect.
Other serious side effects, also rare, may include liver damage, convulsions, coma, and pancreatitis.
Atypical Antipsychotics
Atypical antipsychotics are standard drugs for schizophrenia. They are now proving to be beneficial for bipolar disorder when used alone or in combination with the mood stabilizers that treat mania. These drugs include clozapine (Clozaril) (the first atypical antipsychotic), olanzapine (Zyprexa), risperidone (Risperdal), paliperidone (Invega), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon).
- Olanzapine was the first atypical antipsychotic approved for treatment of bipolar disorder. In 2000, the FDA approved it to treat bipolar mania and mixed states. In 2004, the drug became the first atypical antipsychotic approved for bipolar maintenance treatment.
- Symbyax, a drug that combines olanzapine and the antidepressant fluoxetine, was approved in 2003 for treatment of bipolar depression.
- Risperidone, ziprasidone, and ariprazole are approved for treatment of bipolar mania and mixed states. Paliperidone (Invega), which is chemically related to risperidone, was approved in 2007 for treatment of schizophrenia but has not yet been approved for bipolar disorder.
- Quetiapine is approved for treatment of bipolar mania and bipolar depression, making it the only drug approved for treating both manic and depressive states.
- Clozapine has not been approved for treatment of bipolar disorder, but has shown promise in investigational studies. However, this drug has more significant side effects than other atypical antipsychotics. It poses a risk of white blood cell reduction (agranulocytosis).
Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include:
- Nasal congestion or runny nose
- Drooling
- Dizziness
- Headache
- Drowsiness -- however, these drugs may also cause restlessness and insomnia.
- Constipation
- Rapid heart beat
- Difficulty urinating
- Skin rash
- Increased body temperature
- Confusion, short-term memory problems, disorientation, and impaired attention
- Weight gain -- risk is highest with clozapine and olanzapine, lowest with aripiprazole and ziprasidone
More serious risks include:
- Diabetes (See Diabetes Risk and Atypical Antipsychotics)
- Weight gain and metabolic problems. The risk is highest for olanzapine, and lowest for aripiprazole and ziprasidone.
- Unhealthy cholesterol levels. Particularly with olanzapine, increased risk for high levels of trigylcerides and total cholesterol.
- Seizures
- Heat stroke
- Sudden drop in blood pressure (hypotension)
- A significant drop in white blood cell count (neutropenia) and neutrophils (agranulocytosis) occurs in 1% or more of patients, generally in the first 6 months after starting treatment. Patients should have their white blood count and absolute neutrophil count regularly monitored if they take clozapine.
- Extrapyramidal side effects, which are lack of motor coordination and involuntary movements
- Cataracts and worsening of any existing glaucoma
- Increased prolactin levels -- prolactin is a hormone associated with infertility and impotence. High levels can cause menstrual abnormalities and may increase the risk for osteoporosis and possibly breast cancer.
Diabetes Risk and Atypical Antipsychotics. In 2003, the FDA requested that the strongest warning be added to the product labels of all atypical antipsychotics. This so-called black box warning advises that these drugs can increase the risk of high blood sugar (hyperglycemia) and diabetes. (Olanzapine is more likely to cause high blood sugar levels than other atypical antipsychotic medicines.) The FDA recommends that:
- Patients with an established diagnosis of diabetes who begin atypical antipsychotic treatment should be regularly monitored for worsening of blood sugar control.
- Patients with risk factors for diabetes (obesity, family history of diabetes) should undergo fasting blood sugar testing at the beginning of atypical antipsychotic treatment and periodically during treatment.
- All patients treated with atypical antipsychotics should be monitored for high blood sugar (hyperglycemia) symptoms.
- Patients who develop hyperglycemia symptoms should undergo fasting blood sugar testing.
Antidepressants
Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They may trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.
Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.
Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. Another antidepressant, venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.
Side effects of SSRIs include:
- Nausea and gastrointestinal problems, which usually wear off over time
- Agitation, insomnia, mild tremor, and impulsivity
- Dry mouth, which can increase the risk for cavities and mouth sores
- Headache
- Sexual dysfunction
Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.
Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.
Other Treatments
Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is a non-drug treatment for bipolar disease and other mental disorders, such as severe depression. It is commonly called shock therapy. ECT has received bad press since it was introduced in the 1930s. But, over the years it has been refined, and is now considered a very safe treatment.
Research suggests ECT may be particularly beneficial for:
- Patients who need immediate stabilization of their condition and who cannot wait for medications to work
- Most patients with mania -- especially elderly patients with severe mania
- Patients who suffer suicidal thoughts and guilt during the depressive phase
- Pregnant patients
- Patients who cannot tolerate drug treatments
- Patients with certain types of heart problems
- Young patients
In a review of studies, about 80% of ECT-treated patients experienced improvement, and for some, it is the only treatment that works.
The Procedure. ECT is performed on an outpatient basis and does not require hospitalization. In general, the ECT procedure is performed as follows:
- A muscle relaxant and short-acting anesthetic are given to the patient.
- A small amount of electricity is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
- The response to ECT is usually very fast, and the patient often needs less medication afterward.
Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Taking the drug naloxone immediately before ECT may help reduce its effects on concentration and some (but not all) forms of memory impairment. Concerns about permanent memory loss appear to be unfounded.
Biologic Effects of ECT on Bipolar Disorder. The precise way that ECT benefits patients with bipolar disorder is not clear. ECT may help by:
- Causing changes in the brain's physiology. For example, ECT may increase the permeability of the blood-brain barrier, produce an antiseizure effect (similar to the effects of antiseizure drugs used as mood stabilizers), and reduce blood flow in parts of the brain associated with improved mood.
- Causing various hormonal changes, particularly with thyroid-related hormones.
- Balancing dopamine levels. This brain chemical plays an important role in bipolar disorder as well as other conditions for which ECT is sometimes recommended, including delusional depression.
- Stimulating growth of neurons in the hippocampus (the area in the brain responsible for memory).
Some studies are finding that maintenance electroconvulsive therapy (ECT) may be helpful for patients who do not respond to medications. In one study of patients with bipolar disorder, those who had intractable recurrent episodes received monthly ECT treatments for more than a year and a half. Without ECT, those patients spent an average of almost half a year in the hospital, suffering at least three episodes annually. After ECT, all the rapid cyclers achieved full or partial remission.
Experimental Procedures
Transcranial Magnetic Stimulation. Repeated transcranial magnetic stimulation (rTMS) is also being studied for unipolar and bipolar depression. Unlike ECT, this procedure does not appear to cause seizures, memory lapses, or impaired thinking. The only common side effect is a mild headache.
Therapy and Lifestyle Changes
Psychotherapy is an important addition to medication. Many approaches are proving to be very useful. Trained mental health professionals can:
- Educate patients about bipolar disorder and its treatments
- Teach patients to recognize and manage early warning symptoms of imminent manic or depressive episodes
- Help them comply with drug regimens
- Monitor the patient's on-going status
- Intervene early in manic and depressive episodes to reduce the severity of the attack
In addition, psychotherapy can help patients:
- Adjust to the reality of the illness and understand the negative consequences of mania -- particularly important for patients who consider their mania to be positive, creative, and exhilarating
- Cope with feelings of guilt and remorse that occur after manic episodes
- Deal with feelings of imperfection and despair
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 one recent study, patients who were given mood stabilizers and underwent a CBT program that was specifically designed to prevent relapse experienced fewer and shorter episodes and improved social functioning compared to those on mood stabilizers alone.
Using Cognitive-Behavioral Therapy for Bipolar Disorder. Typical goals of CBT for bipolar disorder patients include learning how to:
- Recognize manic episodes before they become full-blown and change behaviors during an episode
- Cope with depression by developing behaviors and thoughts that may help offset the negative mood
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.
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
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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.
