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* This is the Professional Version. *

Bipolar Disorders

By William Coryell, MD, University of Iowa

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Patient Education

Bipolar disorders are characterized by episodes of mania and depression, which may alternate, although many patients have a predominance of one or the other. 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 mood-stabilizing drugs, sometimes with psychotherapy.

Bipolar disorders usually begin in the teens, 20s, or 30s. Lifetime prevalence is about 4%. Rates of bipolar I disorder are about equal for men and women.

Bipolar disorders are classified as

  • Bipolar I disorder: Defined by the presence of at least one full-fledged (ie, disrupting normal social and occupational function) manic episode and usually depressive episodes

  • Bipolar II disorder: Defined by the presence of major depressive episodes with at least one hypomanic episode but no full-fledged manic episodes

  • Unspecified bipolar disorder: Disorders with clear bipolar features that do not meet the specific criteria for other bipolar disorders

In cyclothymic disorder, patients have prolonged (> 2-yr) periods that include both hypomanic and depressive episodes; however, these episodes do not meet the specific criteria for a bipolar disorder.

Etiology

Exact cause of bipolar disorder is unknown. Heredity plays a significant role. There is also evidence of dysregulation of serotonin and norepinephrine. Psychosocial factors may be involved. Stressful life events are often associated with initial development of symptoms and later exacerbations, although cause and effect have not been established.

Certain drugs can trigger exacerbations in some patients with bipolar disorder; these drugs include

Symptoms and Signs

Bipolar disorder begins with an acute phase of symptoms, followed by a repeating course of remission and relapse. Remissions are often complete, but many patients have residual symptoms, and for some, the ability to function at work is severely impaired. Relapses are discrete episodes of more intense symptoms that are manic, depressive, hypomanic, or a mixture of depressive and manic features.

Episodes last anywhere from a few weeks to 3 to 6 mo.

Cycles—time from onset of one episode to that of the next—vary in length among patients. Some patients have infrequent episodes, perhaps only a few over a lifetime, whereas others have rapid-cycling forms (usually defined as 4 episodes/yr). Only a minority alternate back and forth between mania and depression with each cycle; in most, one or the other predominates to some extent.

Patients may attempt or commit suicide. Lifetime incidence of suicide in patients with bipolar disorder is estimated to be at least 15 times that of the general population.

Mania

A manic episode is defined as 1 wk of a persistently elevated, expansive, or irritable mood and persistently increased goal-directed activity or energy plus 3 additional symptoms:

  • Inflated self-esteem or grandiosity

  • Decreased need for sleep

  • Greater talkativeness than usual

  • Flight of ideas or racing of thoughts

  • Distractibility

  • Increased goal-directed activity

  • Excessive involvement in activities with high potential for painful consequences (eg, buying sprees, foolish business investments)

Manic patients may be inexhaustibly, excessively, and impulsively involved in various pleasurable, high-risk activities (eg, gambling, dangerous sports, promiscuous sexual activity) without insight into possible harm. Symptoms are so severe that they cannot function in their primary role (occupation, school, housekeeping). Unwise investments, spending sprees, and other personal choices may have irreparable consequences.

Patients in a manic episode may be exuberant and flamboyantly or colorfully dressed and often have an authoritative manner with a rapid, unstoppable flow of speech. Patients may make clang associations (new thoughts that 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 cause patients to feel that they are being unjustly treated or persecuted. As a result, patients may become a danger to themselves or to other people. Accelerated mental activity is experienced as racing thoughts by patients and is observed as flights of ideas by the physician.

Manic psychosis is a more extreme manifestation, with psychotic symptoms that may be difficult to distinguish from schizophrenia. Patients may have extreme grandiose or persecutory delusions (eg, of being Jesus or being pursued by the FBI), occasionally with hallucinations. Activity level increases markedly; patients may race about and scream, swear, or sing. Mood lability increases, often with increasing irritability. Full-blown delirium (delirious mania) may appear, with complete loss of coherent thinking and behavior.

Hypomania

A hypomanic episode is a less extreme variant of mania involving a distinct episode that lasts 4 days with behavior that is distinctly different from the patient’s usual nondepressed self and that includes 3 of the additional symptoms listed above under mania.

During the hypomanic period, mood brightens, the need for sleep decreases, and psychomotor activity accelerates. For some patients, hypomanic periods are adaptive because they produce high energy, creativity, confidence, and supernormal social functioning. Many do not wish to leave the pleasurable, euphoric state. Some function quite well, and in most, functioning is not markedly impaired. However, in some patients, hypomania manifests as distractibility, irritability, and labile mood, which the patient and others find less attractive.

Depression

A depressive episode has features typical of major depression; the episode must include ≥ 5 of the following during the same 2-wk period, and one of them must be depressed mood or loss of interest or pleasure:

  • Depressed mood most of the day

  • Markedly diminished interest or pleasure in all or almost all activities for most of the day

  • Significant (> 5%) weight gain or loss or decreased or increased appetite

  • Insomnia (often sleep-maintenance insomnia) or hypersomnia

  • Psychomotor agitation or retardation observed by others (not self-reported)

  • Fatigue or loss of energy

  • Feelings of worthlessness or excessive or inappropriate guilt

  • Diminished ability to think or concentrate or indecisiveness

  • Recurrent thoughts of death or suicide, a suicide attempt, or specific plan for suicide

Psychotic features are more common in bipolar depression than in unipolar depression.

Mixed features

An episode of mania or hypomania is designated as having mixed features if ≥ 3 depressive symptoms are present for most days of the episode. This condition is often difficult to diagnose and may shade into a continuously cycling state; the prognosis is worse than that in a pure manic or hypomanic state.

Risk of suicide during mixed episodes is particularly high.

Diagnosis

  • Clinical criteria ( Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition)

  • Thyroxine (T4) and TSH levels to exclude hyperthyroidism

  • Exclusion of stimulant drug abuse clinically or by urine testing

Diagnosis of bipolar disorder is based on identification of symptoms of mania or hypomania as described above, plus a history of remission and relapse. Symptoms must be severe enough to markedly impair social or occupational functioning or to require hospitalization to prevent harm to self or others.

Some patients who present with depressive symptoms may have previously experienced hypomania or mania but 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), although such information is more likely to be provided by relatives. A structured inventory such as the Mood Disorder Questionnaire may be useful. All patients must be asked gently but directly about suicidal ideation, plans, or activity.

Similar acute manic or hypomanic symptoms may result from stimulant abuse or physical disorders such as hyperthyroidism or pheochromocytoma. Patients with hyperthyroidism typically have other physical symptoms and signs, but thyroid function testing (T4 and TSH levels) is a reasonable screen for new patients. Patients with pheochromocytoma are markedly hypertensive; if they are not, testing is not indicated. Other disorders less commonly cause symptoms of mania, but depressive symptoms may occur in a number of disorders (see Table: Some Causes of Symptoms of Depression and Mania).

A review of substance use (especially of amphetamines and cocaine) and urine drug screening can help identify drug causes. However, because drug use may simply have triggered an episode in a patient with bipolar disorder, seeking evidence of symptoms (manic or depressive) not related to drug use is important.

Some patients with schizoaffective disorder have manic symptoms, but such patients rarely return to normal between episodes, and they, unlike most patients with mania, do not show interest in connecting with other people.

Patients with bipolar disorder may also have anxiety disorders (eg, social phobia, panic attacks, obsessive-compulsive disorders), possibly confusing the diagnosis.

Some Causes of Symptoms of Depression and Mania

Type of Disorder

Depression

Mania

Connective tissue

SLE

SLE

Endocrine

Hyperthyroidism

Infectious

General paresis ( parenchymatous neurosyphilis)

TB

Viral hepatitis

Viral pneumonia

AIDS

General paresis

Influenza

St. Louis encephalitis

Neoplastic

Disseminated carcinomatosis

Neurologic

Complex partial seizures (temporal lobe)

Stroke (left frontal)

Complex partial seizures (temporal lobe)

Diencephalic tumors

Head trauma

Multiple sclerosis

Stroke

Nutritional

Other*

Pharmacologic

Amphotericin B

Anticholinesterase insecticides

Barbiturates

Beta-blockers (some, eg, propranolol)

Cimetidine

Corticosteroids

Cycloserine

Estrogen therapy

Indomethacin

Interferon

Mercury

Methyldopa

Metoclopramide

Oral contraceptives

Phenothiazines

Reserpine

Thallium

Vinblastine

Vincristine

Amphetamines

Certain antidepressants

Bromocriptine

Cocaine

Corticosteroids

Levodopa

Methylphenidate

Sympathomimetic drugs

Mental

Dementing disorders in the early phase

*Depression commonly occurs in these disorders, but no causal relationship has been established.

Treatment

  • Mood stabilizers (eg, lithium, certain anticonvulsants), a 2nd-generation antipsychotic, or both

  • Support and psychotherapy

Treatment of bipolar disorder usually has 3 phases:

  • Acute: To stabilize and control the initial, sometimes severe manifestations

  • Continuation: To attain full remission

  • Maintenance or prevention: To keep patients in remission

Although most patients with hypomania can be treated as outpatients, severe mania or depression often requires inpatient management.

Drug treatment of bipolar disorder

  • Mood stabilizers: Lithium and certain anticonvulsants, especially valproate, carbamazepine, and lamotrigine

  • 2nd-generation antipsychotics: Aripiprazole, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone

These drugs are used alone or in combination for all phases of treatment, although at different dosages.

Choice of drug treatment for bipolar disorder can be difficult because all drugs have significant adverse effects, drug interactions are common, and no drug is universally effective. Selection should be based on what has previously been effective and well-tolerated in a given patient. If there is no prior experience (or it is unknown), choice is based on the patient’s medical history (vis-à-vis the adverse effects of the specific mood stabilizer) and the severity of symptoms.

Specific antidepressants (eg, SSRIs) are sometimes added for severe depression, but their effectiveness is controversial; they are not recommended as sole therapy for depressive episodes.

Other treatments

Electroconvulsive therapy (ECT) is sometimes used for depression refractory to treatment and is also effective for mania.

Phototherapy can be useful in treating seasonal bipolar I or bipolar II disorder (with autumn-winter depression and spring-summer hypomania). It is probably most useful as augmentative therapy.

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 adhere to 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.

Support groups (eg, the Depression and Bipolar Support Alliance [ DBSA ]) can help patients by providing a forum to share their common experiences and feelings.

Key Points

  • Bipolar disorder is a cyclic condition that involves episodes of mania with or without depression (bipolar 1) or hypomania plus depression (bipolar 2).

  • Bipolar disorder markedly impairs the ability to function at work and to interact socially, and risk of suicide is significant; however, mild manic states (hypomania) are sometimes adaptive because they can produce high energy, creativity, confidence, and supernormal social functioning.

  • Length and frequency of cycles vary among patients; some patients have only a few over a lifetime, whereas others have 4 episodes/yr (rapid-cycling forms).

  • Only a few patients alternate back and forth between mania and depression during each cycle; in most cycles, one or the other predominates.

  • Diagnosis is based on clinical criteria, but stimulant abuse and physical disorders such as hyperthyroidism or pheochromocytoma must be ruled out by examination and testing.

  • Treatment depends on the manifestations and their severity but typically involves mood stabilizers (eg, lithium, valproate, carbamazepine, lamotrigine) and/or 2nd-generation antipsychotics (eg, aripiprazole, lurasidone, olanzapine, quetiapine, risperidone, ziprasidone).

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • LAMICTAL
  • INDOCIN
  • MARQIBO KIT
  • ABILIFY
  • REGLAN
  • GEODON
  • TAGAMET
  • SEROQUEL
  • TEGRETOL
  • No US brand name
  • LITHOBID
  • ZYPREXA
  • LEVOPHED
  • SEROMYCIN
  • RISPERDAL
  • LATUDA
  • No brand name
  • CONCERTA, RITALIN
  • PARLODEL
  • INDERAL

* This is the Professional Version. *