Bipolar disorder

Definition

Bipolar, or manic-depressive, disorder is a mood disorder that causes radical emotional changes and mood swings, from manic highs to depressive lows. The majority of bipolar individuals experience alternating episodes of mania (an elevated or euphoric mood or irritable state) and depression.

Description

In the United States alone, bipolar disorder afflicts an estimated three million people. According to a report by the National Institutes of Mental Health, the disorder costs over $45 billion annually. The average age of onset of bipolar disorder is from adolescence through the early twenties. However, because of the complexity of the disorder, a correct diagnosis can be delayed for several years or more.

The Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revised ( DSM-IV-TR ), the diagnostic standard for mental health professionals in the United States, defines four separate categories of bipolar disorder: bipolar I, bipolar II, cyclothymia, and bipolar not otherwise specified (NOS).

Bipolar I disorder is characterized by manic episodes, the "high" of the manic-depressive cycle. A bipolar patient experiencing mania often has feelings of self-importance, elation, talkativeness, increased sociability, and a desire to embark on goal-oriented activities, coupled with the characteristics of irritability, impatience, impulsiveness, hyperactivity, and a decreased need for sleep. Usually this manic period is followed by a period of depression, although a few bipolar I individuals may not experience a major depressive episode. Mixed states, where both manic or hypomanic symptoms and depressive symptoms occur at the same time, also occur frequently with bipolar I patients (for example, depression with the racing thoughts of mania). Also, dysphoric mania is common (mania characterized by anger and irritability).

Bipolar II disorder is characterized by major depressive episodes alternating with episodes of hypomania, a milder form of mania. Bipolar depression may be difficult to distinguish from unipolar depression (depression without mania, as found in major depressive disorder ). Patients with bipolar depression tend to have extremely low energy, retarded mental and physical processes, and more profound fatigue (for example, hypersomnia—a sleep disorder marked by a need for excessive sleep or sleepiness when awake) than people with unipolar depression.

Cyclothymia refers to the cycling of hypomanic episodes with depression that does not reach major depressive proportions. A third of patients with cyclothymia will develop bipolar I or II disorder later in life.

A phenomenon known as rapid cycling occurs in up to 20% of bipolar I and II patients. In rapid cycling, manic and depressive episodes must alternate frequently—at least four times in 12 months—to meet the diagnostic definition. In some cases of "ultra-rapid cycling," the patient may bounce between manic and depressive states several times within a 24-hour period. This condition is very hard to distinguish from mixed states.

Bipolar NOS is a category for bipolar states that do not clearly fit into the bipolar I, II, or cyclothymia diagnoses.

Causes and symptoms

The source of bipolar disorder has not been clearly defined. Because two-thirds of bipolar patients have a family history of emotional disorders, researchers have searched for a genetic link to the disorder. Several studies have uncovered a number of possible genetic connections to the predisposition for bipolar disorder. There is significant evidence that correlates bipolar II with genetic causes. Studies have shown that identical twins have an 80% concordance rate (presence of the same disorder). Additionally, studies have demonstrated that the disorder is transmitted to children by autosomal dominant inheritance. This means that either affected parent (father or mother) has a 50% chance of having a child (regardless if the child is male or female) with the disorder.

Further studies concerning the genetic correlations have revealed specific chromosomes (the structures that contain genes) that contain mutated genes. Susceptible genes are located in specific regions of chromosomes 13, 18, and 21. The building blocks of genes, called nucleotides, are normally arranged in a specific order and quantity. If these nucleotides are repeated, a genetic abnormality usually results. Recent evidence suggests that a special type of nucleotide repeat is observed in persons with bipolar II on chromosome 18. However, the presence of this sequence does not worsen the disorder or change the age of onset. It is currently thought that expression of bipolar II involves multiple mutated genes. Further research is ongoing to discover precise mechanisms and to develop genetic markers (gene tags) that would predict which individuals are at higher risk.

Another possible biological cause for bipolar disorder under investigation is the presence of an excessive calcium buildup in the cells. Also, dopamine and other neurochemical transmitters (the chemicals that transmit messages from nerve cell to nerve cell) appear to be implicated in bipolar disorder and these are under intense investigation.

Over half of patients diagnosed with bipolar disorder have a history of substance abuse. There is a high rate of association between cocaine abuse and bipolar disorder. Some studies have shown up to 30% of abusers meeting the criteria for bipolar disorder. The emotional and physical highs and lows of cocaine use correspond to the manic depression of the bipolar patient, making the disorder difficult to diagnose.

For some bipolar patients, manic and depressive episodes coincide with seasonal changes. Depressive episodes are typical during winter and fall, and manic episodes are more probable in the spring and summer months.

Symptoms of bipolar depressive episodes include low energy levels, feelings of despair, difficulty concentrating, extreme fatigue, and psychomotor retardation (slowed mental and physical capabilities). Manic episodes are characterized by feelings of euphoria, lack of inhibitions, racing thoughts, diminished need for sleep, talkativeness, risk taking, and irritability. In extreme cases, mania can induce hallucinations and other psychotic symptoms such as grandiose delusions (ideas that the person affected is extremely important or has some unrecognized talent or insight).

Demographics

Manic-depression is a common psychological disorder that is difficult to detect. As stated, it is estimated that about three million people in the United States are affected. The disorder is more common among women than men. Women have been observed at increased risk of developing subsequent episodes in the period immediately following childbirth.

Diagnosis

Bipolar disorder is usually diagnosed and treated by a psychiatrist and/or a psychologist with medical assistance. In addition to an interview, several clinical inventories or scales may be used to assess the patient's mental status and determine the presence of bipolar symptoms. These include the Millon Clinical Multiaxial Inventory III (MCMI-III), Minnesota Multiphasic Personality Inventory II (MMPI-2), the Internal State Scale (ISS), the Self-Report Manic Inventory (SRMI), and the Young Mania Rating Scale (YMRS). The tests are verbal and/or written and are administered in both hospital and outpatient settings.

Psychologists and psychiatrists typically use the criteria listed in the DSM-IV-TR as a guideline for diagnosis of bipolar disorder and other mental illnesses. DSM-IV-TR describes a manic episode as an abnormally elevated or irritable mood lasting a period of at least one week that is distinguished by at least three of the mania symptoms: inflated self-esteem, decreased need for sleep, talkativeness, racing thoughts, distractibility, increase in goal-directed activity, or excessive involvement in pleasurable activities that have a high potential for painful consequences. If the mood of the patient is irritable and not elevated, four of the symptoms are required.

Although many clinicians find the criteria too rigid, a hypomanic diagnosis requires a duration of at least four days with at least three of the symptoms indicated for manic episodes (four if mood is irritable and not elevated). DSM-IV-TR notes that unlike manic episodes, hypomanic episodes do not cause a marked impairment in social or occupational functioning, do not require hospitalization , and do not have psychotic features (no delusions or hallucinations). In addition, because hypomanic episodes are characterized by high energy and goal-directed activities and often result in a positive outcome, or are perceived in a positive manner by the patient, bipolar II disorder can go undiagnosed.

Bipolar symptoms often appear differently in children and adolescents than they appear in adults. Manic episodes in these age groups are typically characterized by more psychotic features than in adults, which may lead to a misdiagnosis of schizophrenia . Children and adolescents also tend toward irritability and aggressiveness instead of elation. Further, symptoms tend to be chronic, or ongoing, rather than acute, or episodic. Bipolar children are easily distracted, impulsive, and hyperactive, which can lead to a misdiagnosis of attention-deficit/hyperactivity disorder (ADHD). Furthermore, their aggression often leads to violence, which may be misdiagnosed as a conduct disorder .

Substance abuse, thyroid disease, and use of prescription or over-the-counter medication can mask or mimic the presence of bipolar disorder. In cases of substance abuse, the patient must ordinarily undergo a period of detoxification and abstinence before a mood disorder is diagnosed and treatment begins.

Treatment

Bipolar disorder is usually treated with both medical and psychosocial interventions. Psychosocial therapies address both psychological and social issues.

Medical interventions

A combination of mood-stabilizing agents with antidepressants, antipsychotics, and anticonvulsants is used to regulate manic and depressive episodes.

MOOD-STABILIZING AGENTS. Mood-stabilizing agents such as lithium, carbamazepine , and valproic acid (valproate) are prescribed to regulate the manic highs and lows of bipolar disorder:

• Lithium ( lithium carbonate , Cibalith-S, Eskalith, Lithane, Lithobid, Lithonate, Lithotabs) is one of the oldest and most frequently prescribed drugs available for the treatment of bipolar mania and depression. Because the drug takes four to ten days to reach a therapeutic level in the bloodstream, it is sometimes prescribed in conjunction with neuroleptics (other psychiatric drugs) and/or benzodiazepines (medications that ease tension by slowing down the central nervous system) to provide more immediate relief of a manic episode. Lithium has also been shown to be effective in regulating bipolar depression, but is not recommended for mixed mania. Lithium may not be an effective long-term treatment option for rapid cyclers, who typically develop a tolerance for it, or may not respond to it. Possible side effects of the drug include weight gain, thirst, nausea, and hand tremors. Prolonged lithium use may also cause hyperthyroidism (a disease of the thryoid marked by heart palpitations, nervousness, the presence of goiter, sweating, and a wide array of other symptoms.)
• Carbamazepine (Tegretol, Atretol) is an anticonvulsant drug (a drug to treat seizures ) usually prescribed in conjunction with other mood-stabilizing agents. The drug is often used to treat bipolar patients who have not responded well to lithium therapy. Blurred vision and abnormal eye movement are two possible side effects of carbamazepine therapy.
• Valproic acid ( divalproex sodium , or Depakote; valproate, or Depakene) is one of the few drugs available that has been proven effective in treating rapid cycling bipolar and mixed states patients. Valproate is prescribed alone or in combination with carbamazepine and/or lithium. Stomach cramps, indigestion, diarrhea, hair loss, appetite loss, nausea, and unusual weight loss or gain are some of the common side effects of valproate.

ANTIDEPRESSANTS. Because antidepressants may stimulate manic episodes in some bipolar patients, their use is typically short-term. Selective serotonin reuptake inhibitors (SSRIs) or, less often, monoamine oxidase inhibitors (MAO inhibitors) are prescribed for episodes of bipolar depression. Tricyclic antidepressants used to treat unipolar depression may trigger rapid cycling in bipolar patients and are, therefore, not a preferred treatment option for bipolar depression.

• SSRIs, such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), regulate depression by regulating levels of serotonin, a neurotransmitter. Anxiety, diarrhea, drowsiness, headache, sweating, nausea, sexual problems, and insomnia are all possible side effects of SSRIs.
• MAOIs such as tranylcypromine (Parnate) and phenelzine (Nardil) block the action of monoamine oxidase (MAO), an enzyme in the central nervous system. Patients taking MAOIs must cut foods high in tyramine (found in aged cheeses and meats) out of their diet.
• Bupropion (Wellbutrin) is a heterocyclic antidepressant. The exact neurochemical mechanism of the drug is not known, but it has been effective in regulating bipolar depression in some patients. Side effects of bupropion include agitation, anxiety, confusion, tremor, dry mouth, fast or irregular heartbeat, headache, and insomnia.

ADJUNCT TREATMENTS. Adjunct treatments are used in conjunction with a long-term pharmaceutical treatment plan:

• Long-acting benzodiazepines (medications that ease tension by slowing the central nervous system) such as clonazepam (Klonapin) and alprazolam (Xanax) are used for rapid treatment of manic symptoms to calm and sedate patients until mania or hypomania have waned and mood-stabilizing agents can take effect. Sedation is a common effect, and clumsiness, light-headedness, and slurred speech are other possible side effects of benzodiazepines.
• Neuroleptics (antipsychotic medications) such as chlorpromazine (Thorazine) and haloperidol (Haldol) are also used to control mania while a mood stabilizer such as lithium or valproate takes effect. Because neuroleptic side effects can be severe (difficulty in speaking or swallowing, paralysis of the eyes, loss of balance control, muscle spasms, severe restlessness, stiffness of arms and legs, tremors in fingers and hands, twisting movements of body, and weakness of arms and legs), benzodiazepines are generally preferred over neuroleptics.
• ECT, or electroconvulsive therapy , has a high success rate for treating both unipolar and bipolar depression, and mania. However, because of the convenience of drug treatment and the stigma sometimes attached to ECT therapy, ECT is usually employed after all pharmaceutical treatment options have been explored. ECT is given under anesthesia and patients are given a muscle relaxant medication to prevent convulsions. The treatment consists of a series of electrical pulses that move into the brain through electrodes on the patient's head. Although the exact mechanisms behind the success of ECT therapy are not known, it is believed that this electrical current alters the electrochemical processes of the brain, consequently relieving depression. Headaches, muscle soreness, nausea, and confusion are possible side effects immediately following an ECT procedure. Temporary memory loss has also been reported in ECT patients. In bipolar patients, ECT is often used in conjunction with drug therapy.

Calcium channel blockers (nimodipine, or Nimotop), typically used to treat angina and hypotension (low blood pressure), have been found effective, in a few small studies, for treating rapid cyclers. Calcium channel blockers stop the excess calcium buildup in cells that is thought to be a cause of bipolar disorder. They are usually used in conjunction with other drug therapies such as carbamazepine or lithium.

Clozapine (Clozaril) is an antipsychotic medication used to control manic episodes in patients who have not responded to typical mood-stabilizing agents. The drug has also been a useful prophylactic, or preventative treatment, in some bipolar patients. Common side effects of clozapine include tachycardia (rapid heart rate), hypotension, constipation, and weight gain. Agranulocytosis, a potentially serious but reversible condition in which the white blood cells that typically fight infection in the body are destroyed, is a possible side effect of clozapine. Patients treated with the drug should undergo weekly blood tests to monitor white blood cell counts.

Risperidone (Risperdal) is an antipsychotic medication that has been successful in controlling mania in several clinical trials when low doses were administered. The side effects of risperidone are mild compared to many other antipsychotics (constipation, coughing, diarrhea, dry mouth, headache, heartburn, increased length of sleep and dream activity, nausea, runny nose, sore throat, fatigue, and weight gain).

A new potential treatment for bipolar II disorder may be gabapentin , an anticonvulsant that may help treat mania. Recent reports indicate that gabapentin is effective for treating sudden onset bipolar II. Very recent evidence suggests, however, that gabapentin can potentially induce aggressive and disruptive behavior in children treated with this drug for seizures.

rTMS, or repeated transcranial magnetic stimulation is a new and still experimental treatment for the depressive phase of bipolar disorder. In rTMS, a large magnet is placed on the patient's head and magnetic fields of different frequency are generated to stimulate the left front cortex of the brain. Unlike ECT, rTMS requires no anesthesia and does not induce seizures.

Psychosocial interventions

Because bipolar disorder is thought to be biological in nature, psychological therapy is recommended as a companion to, but not a substitute for, pharmaceutical treatment of the disease. Psychotherapy , such as cognitive-behavioral therapy , can be a useful tool in helping patients and their families adjust to the disorder, in encouraging compliance to a medication regimen, and in reducing the risk of suicide . Also, educative counseling is recommended for the patient and family.

In educative counseling, patients (and their families) learn of the high rates of social dysfunction and marital discord associated with this disorder. Patients also learn how their treatment will progress, which factors can affect treatment, and what kind of follow-up after treatment will be implemented. Genetic counseling should be a part of family education programs since this disorder is more prevalent among first-degree relatives of individuals with the disorder.

Social support for individuals with bipolar disorder is also important. Some people with the disorder, as well as their families, may find support groups helpful.

Alternative treatment

General recommendations include maintaining a calm environment, avoiding over-stimulation, getting plenty of rest, regular exercise, and proper diet. Some Chinese herbs may soften mood swings, but care must be taken (and good communication with the physician is essential) when combining herbal therapies with medications. Biofeedback is effective in helping some patients control symptoms such as irritability, poor self-control, racing thoughts, and sleep problems. A diet low in vanadium (a mineral found in meats and other foods) and high in vitamin C may be helpful in reducing depression.

Prognosis

While most patients will show some positive response to treatment, response varies widely, from full recovery to a complete lack of response to all drugs and/or ECT therapy. Drug therapies frequently need adjustment to achieve the maximum benefit for the patient. Bipolar disorder is a chronic recurrent illness in over 90% of those afflicted, and one that requires lifelong observation and treatment after diagnosis. Patients with untreated or inadequately treated bipolar disorder have a suicide rate of 15-25% and a nine-year decrease in life expectancy. With proper treatment, the life expectancy of the bipolar patient increases by nearly seven years and work productivity increases by ten years.

Prevention

The ongoing medical management of bipolar disorder is critical to preventing relapse (recurrence) of manic episodes. Even in carefully controlled treatment programs, bipolar patients may experience recurring episodes of the disorder. Patient education in the form of psychotherapy or self-help groups is crucial for training bipolar patients to recognize signs of mania and depression and to take an active part in their treatment program.

Resources

BOOKS

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text revised. Washington, DC: American Psychiatric Press, Inc., 2000.

Maxmen, Jerrold S. and Nicholas G. Ward. "Mood Disorders." In Essential Psychopathology and Its Treatment. 2nd ed. New York: W. W. Norton, 1995.

Tasman, Allan, Jerald Kay MD, and Jeffrey A. Lieberman MD, eds. Psychiatry. 1st edition. Philadelphia: W. B. Saunders, Co., 1997.

Whybrow, Peter C. A Mood Apart. New York: Harper Collins, 1997.

PERIODICALS

Keck, P., S. McElroy, L. Arnold. "Advances in the pathophysiology and treatment of psychiatric disorders: implications for internal medicine." Medical clinics of North America 85, no. 3 (May 2001).

Kilzieh, N., and H. Akiskal. "Rapid-cycling bipolar disorder: an overview of research and clinical experience." Psychiatric Clinics of North America 22, no. 3 (September 1999).

ORGANIZATIONS

American Psychiatric Association. 1400 K Street NW, Washington DC 20005. (888) 357-7924. <http://www.psych.org> .

National Alliance for the Mentally Ill (NAMI). Colonial Place Three, 2107 Wilson Blvd., Ste. 300, Arlington, VA 22201-3042. (800) 950-6264. <http://www.nami.org> .

National Depressive and Manic-Depressive Association (NDMDA). 730 N. Franklin St., Suite 501, Chicago, IL 60610. (800) 826-3632. <http://www.ndmda.org> .

National Institute of Mental Health. Mental Health Public Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville, MD 20857. (888) 826-9438. <http://www.nimh.nih.gov> .

Paula Anne Ford-Martin, M.A. Laith Farid Gulli, M.D. Nicole Mallory, M.S., PA-C