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Bipolar
disorders are characterized by mania and depression, which usually
alternate. Exact cause is unknown, but heredity, changes in the
level of brain neurotransmitters, and psychosocial factors may be
involved. Diagnosis is based on history. Treatment consists of drugs,
sometimes with psychotherapy.
Bipolar disorders usually begin in the teens, 20s, or 30s. Lifetime prevalence is about 1%. Rates are about equal for men and women.
Bipolar disorders are classified partly based on long-term patterns of episodes of more intense symptoms as bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified (NOS). Forms associated with a disorder or drug use are classified as bipolar disorder due to their general physical condition or substance-induced bipolar disorder.
Etiology
Exact cause is unknown. Heredity plays some role. There is also evidence of dysregulation of serotonin and norepinephrine . Psychosocial factors may also be involved. Stressful life events are often associated with initial development of symptoms and later exacerbations, although cause and effect have not been established.
Bipolar disorders or symptoms of bipolar disorders can occur with several physical disorders, as adverse effects of many drugs, or as part of several other mental disorders (see Table 1: Mood Disorders: Some Causes of Symptoms of Depression and Mania ).
Symptoms and Signs
Bipolar disorder begins with an acute phase of symptoms and is followed by a repeating course of relapse and remission. Relapses are episodes marked by more intense symptoms, lasting about 3 to 6 mo. Episodes are manic, depressive, hypomanic, or a mixture (of depressive and manic features). Cycles—time from onset of one episode to that of the next—vary in length. Cyclicity is particularly accentuated in rapid-cycling forms of bipolar disorder (usually defined as ≥ 4 episodes/yr). Disruption of developmental and social functioning is common, especially when onset occurs between ages 13 and 18.
Psychotic symptoms may be present. In full-blown manic psychosis, the mood is usually elation, but irritability and frank hostility with cantankerousness are not uncommon.
Bipolar
I disorder is defined by alternation of full-fledged manic and major depressive episodes. It commonly begins with depression. Depression can occur immediately before or after mania, or depression and mania can be separated by months or years.
Bipolar
II disorder is defined by a history of at least one major depressive episode and at least one hypomanic episode. Depressive episodes alternate with hypomania. During the hypomanic period, mood brightens, the need for sleep decreases, and psychomotor activity accelerates. Often, the switch follows circadian factors (eg, going to bed depressed and waking early in the morning in a hypomanic state). Hypersomnia and overeating are characteristic and may recur seasonally (eg, in autumn or winter); insomnia and poor appetite occur during the depressive phase. For some patients, hypomanic periods are adaptive because they produce high energy, confidence, and supernormal social functioning.
Bipolar
disorder NOS refers to disorders with clear bipolar features that do not meet the specific criteria for other bipolar disorders.
Mania:
A manic episode is defined as ≥ 1 wk of a persistently elevated, expansive, or irritable mood, accompanied by ≥ 3 additional symptoms: inflated self-esteem or grandiosity, decreased need for sleep, greater talkativeness than usual, persistent elevation of mood, flight of ideas or racing of thoughts, distractibility, increased goal-directed activity, and excessive involvement in pleasurable activities with a higher risk of undesirable consequences (eg, injury, loss of money). Symptoms impair functioning.
Typically, patients in a manic episode are exuberant and flamboyantly or colorfully dressed; they have an authoritative manner with a rapid, unstoppable flow of speech. Patients make clang associations: New thoughts are triggered by word sounds rather than meaning. Easily distracted, patients may constantly shift from one theme or endeavor to another. However, they tend to believe they are in their best mental state. Lack of insight and an increased capacity for activity often lead to intrusive behavior and can be a dangerous combination. Interpersonal friction results and may lead to paranoid delusions that they are being unjustly treated or persecuted. Accelerated mental activity is experienced as racing thoughts by patients, is observed as flights of ideas by the physician, and, in its extreme form, is difficult to distinguish from the loose associations of schizophrenia. Psychotic symptoms develop in some patients with bipolar I disorder. Need for sleep is decreased. Manic patients are inexhaustibly, excessively, and impulsively involved in various activities without recognizing the inherent social dangers.
Hypomania:
A hypomanic episode is a distinct episode of ≥ 4 days that is distinctly different from the patient's usual nondepressed mood. The episode is marked by ≥ 4 symptoms that occur during a manic episode, but the symptoms are relatively less intense, so that functioning is not markedly impaired.
Mixed
state:
A mixed episode blends depressive and manic or hypomanic features. The most typical examples are momentary switches to tearfulness during the height of mania or racing thoughts during a depressive period. In at least 1⁄3 of people with bipolar disorder, the entire episode is mixed. A common presentation consists of a dysphorically excited mood, crying, curtailed sleep, racing thoughts, grandiosity, psychomotor restlessness, suicidal ideation, persecutory delusions, auditory hallucinations, indecisiveness, and confusion. This presentation is called dysphoric mania (ie, prominent depressive symptoms superimposed on manic psychosis).
Diagnosis
Some patients who experience hypomania or mania do not report it unless they are specifically questioned. Skillful questioning may reveal morbid signs (eg, excesses in spending, impulsive sexual escapades, stimulant drug abuse). Such information is more likely to be provided by relatives. Diagnosis is based on the symptoms and signs described above. All patients must be asked gently but directly about suicidal ideation, plans, or activity.
A review of substance (especially amphetamines, particularly methamphetamine—see Drug Use and Dependence: Amphetamines) and prescription drug use and of body systems is needed to exclude drugs and physical disorders. Although no laboratory findings are pathognomonic for bipolar disorders, routine blood tests should be done to screen for physical disorders; thyroid-stimulating hormone (TSH) excludes hyperthyroidism. Other physical disorders (eg, pheochromocytoma) occasionally confuse the diagnosis. Anxiety disorders (eg, social phobia, panic attacks, obsessive-compulsive disorders) may also confuse the diagnosis.
Prognosis
and Treatment
Most patients with hypomania can be treated as outpatients. Acute mania usually requires inpatient management. Typically, mood stabilizers are used to induce remission in patients with acute mania or hypomania. Lithium and certain anticonvulsants, especially valproate , carbamazepine , oxcarbazepine , and lamotrigine , act as mood stabilizers and are similarly effective. Choice of a mood stabilizer depends on the patient's medical history and adverse effects of the specific mood stabilizer.
Two thirds of patients with uncomplicated bipolar disorder respond to lithium . Several therapeutic mechanisms have been proposed but are unproved. Predictors of a good response include a euphoric mania as part of a primary mood disorder, < 2 episodes/yr, and a personal and family history of response to lithium . Lithium is less effective in patients with a mixed state, rapid-cycling forms of bipolar disorder, comorbid anxiety, substance abuse, or a neurologic disorder.
Lithium carbonate is started at 300 mg po bid or tid and increased over 7 to 10 days until a blood level of 0.8 to 1.2 mEq/L is reached. Lithium levels should be maintained between 0.8 and 1.0 mEq/L, usually by giving 450 to 900 mg sustained-release po bid. Adolescents, whose glomerular function is excellent, need higher doses of lithium ; elderly patients need lower doses. During a manic episode, patients retain lithium and excrete Na; oral dosage and lithium blood level need to be higher during acute treatment than during maintenance prophylaxis.
Because lithium 's onset of action has a 4- to 10-day latency period, an antipsychotic may be necessary initially; it is given as needed until the manic stage is controlled. Acute manic psychosis is being increasingly managed with 2nd-generation antipsychotics, such as risperidone (usually 4 to 6 mg po once/day), olanzapine (usually 10 to 20 mg po once/day), quetiapine (200 to 400 mg po bid), ziprasidone (40 to 80 mg po bid), and aripiprazole (10 to 30 mg once/day) because risk of extrapyramidal adverse effects is minimal. For extremely hyperactive psychotic patients with poor food and fluid intake, giving an antipsychotic IM with supportive care for 1 wk before initiating lithium is preferable. Noncompliant, cantankerous manic patients are customarily given a depot phenothiazine (eg, fluphenazine 12.5 to 25 mg IM q 3 to 4 wk) instead of an oral antipsychotic. Many patients with bipolar disorder and mood-incongruent psychotic features beyond the usual boundaries of pure mood disorder require intermittent courses of depot antipsychotics. Lorazepam or clonazepam 2 to 4 mg IM or po tid given early in acute management can reduce the doses need of the antipsychotic.
Although lithium attenuates bipolar mood swings, it has no effect on normal mood. It also appears to have an antiaggressive action, but whether this action occurs in people without a bipolar disorder is unclear. Lithium can cause sedation and cognitive impairment directly or indirectly by causing hypothyroidism. The most common acute, mild adverse effects are fine tremor, fasciculation, nausea, diarrhea, polyuria, thirst, polydipsia, and weight gain (partly attributed to drinking high-calorie beverages). These effects are usually transient and often respond to decreasing the dose slightly, dividing the dose (eg, tid), or using slow-release forms. Once dosage is established, the entire dose should be given after the evening meal. This dosing may improve compliance, and the troughs in blood levels are believed to protect the kidneys. A β-blocker (eg, atenolol 25 to 50 mg po once/day) can control severe tremor. Some β-blockers may worsen depression.
Lithium toxicity is manifested initially by gross tremor, increased deep tendon reflexes, persistent headache, vomiting, and confusion and may progress to stupor, seizures, and arrhythmias. Toxicity is more likely to occur in elderly patients and in patients with decreased creatinine clearance or with Na loss, which may result from fever, vomiting, diarrhea, or use of diuretics. NSAIDs other than aspirin may contribute to hyperlithemia. Lithium blood levels should be measured, including each time the dose is changed and at least q 6 mo. Lithium may precipitate hypothyroidism, particularly when there is a family history of hypothyroidism. Therefore, TSH levels should be monitored when lithium is started and at least annually if there is a family history or if symptoms suggest thyroid dysfunction or at least biannually for all other patients.
Lithium commonly and chronically exacerbates acne and psoriasis and can cause nephrogenic diabetes insipidus, which may respond to dose reduction or temporary interruption of lithium . Patients with a history of parenchymal renal disease may be at risk of structural damage to the distal tubule. Renal function should be assessed at baseline, and serum creatinine levels should be monitored over time.
Anticonvulsants that act as mood stabilizers, especially valproate , carbamazepine , and oxcarbazepine , are often used for acute mania and for mixed states (mania and depression). Their precise therapeutic action in bipolar disorder is unknown but may involve γ-aminobutyric acid mechanisms and ultimately G-protein signaling systems. Their main advantages over lithium include a wider therapeutic margin and lack of renal toxicity. The loading dose is 20 mg/kg, then 250 to 500 mg po tid for valproate . Carbamazepine should not be loaded; the dose should be increased gradually to reduce risk of toxicity. Oxcarbazepine has fewer adverse effects and is moderately effective.
Combining mood stabilizers is often necessary for optimal results, especially when episodes of mania or mixed states are severe. Electroconvulsive therapy is sometimes used for cases refractory to mood stabilizers.
Treatment of an initial manic or hypomanic episode with a mood stabilizer should continue for at least 6 mo, then tapered and stopped. The mood stabilizer is restarted for recurrent episodes and maintained if episodes are < 3 yr apart. Maintenance therapy with lithium should be initiated after 2 classic manic episodes < 3 yr apart.
In patients with recurrences, depressive episodes should be treated with antidepressants and mood stabilizers (the anticonvulsant lamotrigine may be particularly effective) because antidepressants (especially heterocyclics), given alone, may trigger hypomania.
Prevention
of rapid cycling:
Antidepressants, even when given with a mood stabilizer, can induce rapid cycling in some patients (eg, patients with bipolar II disorder). Antidepressants should not be used prophylactically unless previous depressive episodes have been severe and, if used, should be given for only 4 to 12 wk. When disruptive psychomotor acceleration or mixed states supervene, adding 2nd-generation antipsychotics (eg, risperidone , olanzapine , quetiapine ) to the regimen can stabilize the patient.
For an established case of rapid cycling, antidepressants, stimulants, caffeine, benzodiazepines, and alcohol must be gradually stopped. Hospitalization may be required. Lithium (or divalproex ) may be given with bupropion . Carbamazepine may also be useful. Some experts combine an anticonvulsant with lithium , trying to keep both drugs at ½ to 2⁄3 their usual dose and blood levels in an appropriate and safe range. Because borderline hypothyroidism also predisposes to rapid cycling (especially in women), TSH should be checked. Thyroid replacement should be given if TSH is high.
Phototherapy:
Phototherapy is a relatively new approach to seasonal bipolar or bipolar II disorder (with autumn-winter depression and spring-summer hypomania). It is probably most useful as augmentation (see Mood Disorders: Phototherapy).
Precautions
during pregnancy:
Most drugs used to treat bipolar disorder must be tapered and stopped before pregnancy or during early pregnancy. Women who wish to have a baby should have at least 2 yr of maintenance therapy with no episodes before lithium is stopped. Lithium is stopped during the 1st trimester to avoid risk of Epstein's anomaly, a heart defect. Carbamazepine and divalproex should also be stopped during the 1st trimester because they may cause neural tube defects. Other mood stabilizers (eg, lamotrigine , oxcarbazepine ), if absolutely necessary, can be used during the 2nd and 3rd trimesters but should be stopped 1 to 2 wk before delivery and resumed a few days postpartum. For a severe relapse during the 1st trimester, electroconvulsive therapy is safer. For early manic recurrence, potent antipsychotics are relatively safe. Women taking mood stabilizers should not breastfeed because these drugs pass into the milk.
Education
and psychotherapy:
Enlisting the support of loved ones is crucial to preventing major episodes. Group therapy is often recommended for patients and their partner; there, they learn about bipolar disorder, its social sequelae, and the central role of mood stabilizers in treatment. Individual psychotherapy may help patients better cope with problems of daily living and adjust to a new way of identifying themselves.
Patients, particularly those with bipolar II disorder, may not comply with mood-stabilizer regimens because they believe that these drugs make them less alert and creative. The physician can explain that decreased creativity is relatively uncommon because mood stabilizers usually provide opportunity for a more even performance in interpersonal, scholastic, professional, and artistic pursuits.
Patients should be counseled to avoid stimulant drugs and alcohol, to minimize sleep deprivation, and to recognize early signs of relapse. If patients tend to be financially extravagant, finances should be turned over to a trusted family member. Patients with a tendency to sexual excesses should be given information about conjugal consequences (eg, divorce) and infectious risks of promiscuity, particularly AIDS. (See also the American Psychiatric Association's practice guideline Treating
Bipolar Disorder: A Quick Reference Guide.)
Last full review/revision November 2005
Content last modified November 2005
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