Bipolar disorders are characterized by episodes of mania and depression, which may alternate, although many patients have a predominance of one or the other. The 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 (see also Bipolar Disorder in Children and Adolescents). Lifetime prevalence is about 4%.

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. Incidence is about equality between men and women.
• Bipolar II disorder: Defined by the presence of major depressive episodes with at least one hypomanic episode but no full-fledged manic episodes. Incidence is somewhat higher for females.
• 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-year) periods that include both hypomanic and depressive episodes; however, these episodes do not meet the specific criteria for bipolar or major depressive disorder.

 

• Etiology of Bipolar Disorder

The exact cause of bipolar disorder is unknown. Heredity plays a significant role. There is also evidence of dysregulation of the neurotransmitters serotonin, norepinephrine, and dopamine.

Psychosocial factors may be involved. Stressful life events are often associated with the 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

• Sympathomimetics (eg, cocaine, amphetamines)
• Alcohol
• Certain antidepressants (eg, tricyclics, noradrenergic reuptake inhibitors)

 

• Symptoms and Signs of Bipolar Disorders

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 months; depressive episodes typically last longer than manic or hypomanic ones.

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/year). Only a minority alternate back and forth between mania and depression with each cycle; in most, one or the other predominates.

Patients may attempt or complete suicide. The 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 week of a persistently elevated, expansive, or irritable mood and persistently increased goal-directed activity or a noticeable increase of 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 leads to intrusive behaviour 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 a complete loss of coherent thinking and behaviour.

Hypomania

A hypomanic episode is a less extreme variant of mania involving a distinct episode that lasts ≥ 4 days with behaviour 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 as energy noticeably increases, 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 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-week period, and one of them must be depressed mood or loss of interest or pleasure and, with the exception of suicidal thoughts or attempts, all symptoms must be present nearly every day:

• 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 a 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 then worse than that in a pure manic or hypomanic state.

The risk of suicide during mixed episodes is particularly high.

 

• Diagnosis of Bipolar Disorders
• Clinical criteria (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition)
• Thyroxine (T4) and thyroid-stimulating hormone (TSH) levels to exclude hyperthyroidism.
• Exclusion of stimulant drug abuse clinically or by blood or urine testing

Diagnosis of bipolar disorder is based on the identification of symptoms of mania or hypomania as described above, plus a history of remission and relapse. A diagnosis of bipolar I disorder requires manic symptoms 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 have marked intermittent or sustained hypertension; if hypertension is absent, testing for pheochromocytoma 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 blood or 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 have psychotic features that may persist beyond the abnormal mood episodes.

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

 

• Treatment of Bipolar Disorders
• 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 therapy for bipolar disorder

Drugs for bipolar disorder include.

• Mood stabilizers: Lithium and certain anticonvulsants, especially valproate, carbamazepine, and lamotrigine
• 2nd-generation antipsychotics: Aripiprazole, lurasidone, olanzapine, quetiapine, risperidone, ziprasidone, and cariprazine.

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

The 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 the patient has not previously been given drugs to treat bipolar disorder (or drug history is unknown), the 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, selective serotonin reuptake inhibitors [SSRIs]) are sometimes added for severe depression, but their effectiveness is controversial; they are not recommended as sole therapy for depressive episodes. Ketamine infusion has also been shown to be effective in the treatment of severe bipolar depression.

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 depressive symptoms of seasonal (with autumn-winter depression and spring-summer hypomania) or nonseasonal bipolar I or bipolar II disorder. It is probably most useful as augmentative therapy.

Transcranial magnetic stimulation, which is sometimes used to treat severe, resistant depression, has also proven effective in bipolar depression.

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 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 the 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/year (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 use disorder 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, cariprazine).