FDA-approved pharmacologic treatments for bipolar depression

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 26-year-old man is evaluated for a 3-month history of depressed mood, poor concentration, decreased energy, increased sleep, and weight gain. He reports missing many days at work and that his work performance has lagged. He has no suicidal ideation. He states that his current symptoms differ markedly from his usual state of being “highly upbeat and energetic” and having high job performance. He has experienced several 30- to 40-day periods of high energy during which he sleeps little and makes “bad choices” (such as spending sprees and “one-night stands”). He has not experienced hallucinations. Medical history is notable for treatment of depression during college with a 6-month course of sertraline. He stopped the drug when he felt “energetic.” He is currently taking no medications.

Physical examination is unremarkable. Laboratory studies are normal.

Which of the following is the most appropriate treatment?

A: Desipramine
B: Paroxetine
C: Quetiapine
D: Venlafaxine

MKSAP Answer and Critique

The correct answer is C: Quetiapine.

Treatment with the atypical antipsychotic drug quetiapine is appropriate for this patient with bipolar I disorder, which is defined as one or more manic episodes. A manic episode is characterized by at least 7 days of severe, abnormally expansive, euphoric, or irritable mood associated with at least three of the following symptoms (four if irritable mood only): grandiosity or inflated self-esteem, pressured speech, flight of ideas, distractibility, increased goal-directed activity or psychomotor agitation, excessive involvement in pleasurable activities with high potential for adverse consequences (for example, spending sprees or sexual encounters), and lessened need for sleep. Dysfunction is substantial. The episode is not attributable to the physiologic effects of a substance or to another medical condition. Most patients with bipolar I disorder experience depressive episodes and are at an increased risk for suicide. Periods of depression are more frequent than periods of mania or hypomania in patients with bipolar disorder.

In selecting therapy for patients with bipolar disorder, it is paramount to identify the patient’s current phase of illness. For the manic or hypomanic phase of illness, there are 10 different treatments, including one typical antipsychotic agent, lithium, two antiepileptic agents, and six atypical antipsychotic agents. Patients presenting in the depressive phase of illness have two treatment options (quetiapine monotherapy or combination olanzapine-fluoxetine). Different treatment options are available for patients in the maintenance phase of illness. Because identifying the patient’s phase of illness and determining complex treatment choices are required, it is paramount that psychiatrists are involved in the care of patients with bipolar disorder.

This patient has acute depression. FDA-approved pharmacologic treatments for bipolar depression are quetiapine alone and combination olanzapine-fluoxetine. Patients with bipolar depression treated with quetiapine should be monitored for hypersomnolence, weight gain, tardive dyskinesia, and hyperglycemia. Lamotrigine is FDA approved for maintenance treatment of bipolar I disorder. Lamotrigine can be prescribed for patients taking quetiapine who experience unacceptable side effects or no improvement of depression.

Antidepressant monotherapy is not recommended (nor FDA approved) for depressed patients with bipolar disorder given lack of efficacy and risk for switching affected patients to hypomania or mania. Therefore, this patient should not receive desipramine, paroxetine, or venlafaxine.

Key Point

FDA-approved pharmacologic treatments for bipolar depression are quetiapine monotherapy and combination olanzapine-fluoxetine.

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