Causes and symptoms

The source of bipolar disorder has not been clearly defined. Because two-thirds of bipolar patients have a family history of affective or 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. A 2003 study found that schizophrenia and bipolar disorder could have similar genetic causes that arise from certain problems with genes associated with myelin development in the central nervous system. (Myelin is a white, fat-like substance that forms a sort of layer or sheath around nerve fibers.) Another possible biological cause under investigation is the presence of an excessive calcium build-up in the cells of bipolar patients. Also, dopamine and other neurochemical transmitters appear to be implicated in bipolar disorder and these are under intense investigation.

Over one-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 diagnosis.

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 illusions.

Diagnosis

Bipolar disorder usually is 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 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV ) as a guideline for diagnosis of bipolar disorder and other mental illnesses. DSM-IV 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 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. 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 present differently in children and adolescents. 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

Treatment of bipolar disorder is usually by means of medication. A combination of mood stabilizing agents with antidepressants, antipsychotics, and anticonvulsants is used to regulate manic and depressive episodes.

Mood stabilizing agents such as lithium, carbamazepine, and valproate are prescribed to regulate the manic highs and lows of bipolar disorder:

• Lithium (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 sometimes is prescribed in conjunction with neuroleptics and/or benzodiazepines to provide more immediate relief of a manic episode. Lithium also has 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 also may cause hyperthyroidism (a disease of the thryoid that is marked by heart palpitations, nervousness, the presence of goiter, sweating, and a wide array of other symptoms.)
• Carbamazepine (Tegretol, Atretol) is an anticonvulsant drug usually prescribed in conjunction with other mood stabilizing agents. The drug often is 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. Clinical trials continue in an attempt to obtain FDA approval of carbamazepine for use in bipolar treatment.
• Valproate (divalproex sodium, or Depakote; valproic acid, 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. Note: valproate also is approved for the treatment of mania. A 2003 study found that the risk of suicide from death is about two and one-half times higher in people with bipolar disorder taking divalproex than those taking lithium.

Because antidepressants may stimulate manic episodes in some bipolar patients, their use typically is 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 to avoid hypotensive side effects.
• 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.
• 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 usually is 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.

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

• Long-acting benzodiazepines 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, lightheadedness, and slurred speech are other possible side effects of benzodiazepines.
• Neuroleptics such as chlorpromazine (Thorazine) and haloperidol (Haldol) also are 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.
• Psychotherapy and counseling. Because bipolar disorder is thought to be biological in nature, 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 fact, a 2003 report revealed that people on medication for bipolar disorder had better results if they also participated in family-focused therapy.

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

Clozapine (Clozaril) is an atypical 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 atypical 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).

Olanzapine (Zyprexa) is another atypical antipsychotic approved in 2003 for use in combination with lithium or valproate for treatment of acute manic episodes associated with bipolar disorder. Side effects include hypotension (low blood pressure) associated with dizziness, rapid heartbeat, and syncope, or low blood pressure to the point of fainting.

Lamotrigine (Lamictal, or LTG), an anticonvulsant medication, was found to alleviate manic symptoms in a 1997 trial of 75 bipolar patients. The drug was used in conjunction with divalproex (divalproate) and/or lithium. Possible side effects of lamotrigine include skin rash, dizziness, drowsiness, headache, nausea, and vomiting.

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.

Alternative treatment

General recommendations include maintaining a calm environment, avoiding overstimulation, getting plenty of rest, regular exercise, and proper diet. Chinese herbs may soften mood swings. 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 drug 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 will increase by nearly seven years and work productivity increases by ten years.

Prevention

The ongoing medical management of bipolar disorder is critical to preventing relapse, or 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.

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