Bipolar and Related Disorders

Bipolar and related disorders are associated with changes in behavior, energy, sleep, and cognition and characterized by episodic recurrent mania, hypomania, and depression. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes the following disorders in the category of bipolar and related disorders:

• Bipolar I Disorder

• Bipolar II Disorder

• Cyclothymic Disorder

• Substance/Medication-Induced Bipolar and Related Disorder

• Bipolar and Related Disorder Due to Another Medical Condition

• Other Specified Bipolar and Related Disorder

• Unspecified Bipolar and Related Disorder

Diagnosis

Bipolar I and Bipolar II Disorders

The diagnosis of bipolar I disorder requires the occurrence of at least one manic episode, whereas the diagnosis of bipolar II requires at least one major depressive episode plus one or more hypomanic episodes without any manic episodes.

• Manic episodes are defined as periods of elevated, euphoric, irritable, and labile mood occurring for most of the day for at least one week. Patients may also exhibit associated symptoms of disinhibition or disregard for expected social boundaries.

• Hypomanic episodes consist of periods of elevated mood lasting at least 4 days (but not as long as one week) and include features of manic episodes with reduced severity of symptoms. For example, patients may express flight of ideas in manic episodes, but formation of thought may be more organized in hypomanic episodes.

The following table describes the DSM-5 diagnostic criteria for distinguishing bipolar I from bipolar II disorder:

Cyclothymic Disorder

The DSM-5 defines cyclothymic disorder as the presence of hypomanic and depressive symptoms that do not meet the criteria for either a hypomanic episode or a major depressive episode. During a period of at least 2 years, hypomanic and depressive periods are present for at least half the time and individuals are not symptom-free for more than 2 consecutive months.

Substance/Medication-Induced Bipolar and Related Disorder

Diagnostic criteria include an altered-mood episode that is due to substance intoxication or withdrawal or exposure to a medication that does not persist beyond the effect of the substance or medication. Cocaine or phencyclidine (PCP) can cause these mood disturbances. Medications such as glucocorticoids can also cause symptoms of mania. These conditions must all be considered in patients with mood elevations.

Bipolar and Related Disorder Due to Another Medical Condition

The presence of manic or hypomanic episodes where the history and examination indicate the presence of another medical condition (e.g., multiple sclerosis, stroke, or endocrine disturbances). Mood disorders often follow the diagnosis of these conditions.

Other Specified Bipolar and Related Disorder or Unspecified Bipolar and Related Disorder

This diagnosis replaces the DSM-IV category of Bipolar Disorder Not Otherwise Specified. It includes symptoms characteristic of bipolar or related disorder that may be clinically impairing but do not meet the strict criteria for bipolar I, II, or cyclothymic disorders because of variation in the duration of episodes or severity. If the clinician explains why criteria are not met, the diagnosis is considered specified. If no reason is given, the diagnosis is considered unspecified.

Treatment

Acute Mania

Treatment recommendations for acute episodes of mania include the following:

• Hospitalization may be necessary to stabilize environmental stimuli and protect the patient from harming themselves or others.

• Begin with a first-line monotherapy or combination therapy (e.g., lithium, quetiapine, divalproex alone, or quetiapine plus lithium/divalproex).

• For more-rapid control (e.g., in patients with agitation or who pose a safety threat to themselves or others), start with combination therapy.

• Treatment choices depend on clinical features. If a patient is uncooperative, medications with intramuscular (IM) or intravenous (IV) routes may be easier to administer.

The use of antidepressants in the management of bipolar depression is controversial and potentially problematic because antidepressants can induce new episodes of mania. In one study, adjunctive antidepressant therapy with a mood stabilizer was not associated with increased rates of durable recovery.

Maintenance Therapy for Bipolar Disorder

Choice of medication or combinations of medications for maintenance therapy are based on efficacy, safety, and tolerability. Patients may need to try a series of adjustments (additions and subtractions) to achieve the best effect. A history of response to a medication may be helpful. Consideration should also be given to comorbid psychiatric conditions and the polarity of the disorder (manic vs. depression predominant polarity). For bipolar 1 disorder, medications shown to be effective in the acute phase should be continued in the maintenance phase of treatment to reduce the risk of relapse.

• Lithium, divalproex, and atypical antipsychotics (e.g., quetiapine, olanzapine, aripiprazole, and risperidone) are all first-line treatments for maintenance therapy in bipolar disorder.

  • Divalproex is associated with teratogenic risk and should be used with caution in women of child-bearing age.

  • Chronic use of lithium increases risk of kidney injury and should be avoided in patients with renal failure.

• Some evidence supports the use of the antipsychotics haloperidol and carbamazepine for maintenance therapy, but they are considered second-line treatment because of safety and tolerability.

The following table summarizes approved drugs for management of bipolar disorder:

(Source: Bipolar Disorder. N Engl J Med 2020.)