A patient with bipolar I disorder on lithium monotherapy experiences a breakthrough manic episode. His lithium level is 0.7 mEq/L. The psychiatrist decides to add an antipsychotic. Which second-generation antipsychotic has the STRONGEST evidence for acute mania AND is LEAST likely to cause metabolic syndrome?
- A Olanzapine
- B Quetiapine
- C Aripiprazole ✓
- D Clozapine
Correct answer: C. Aripiprazole
Explanation
Aripiprazole is a dopamine partial agonist (D2 partial agonist, 5-HT1A partial agonist, 5-HT2A antagonist) with robust FDA approval for acute manic/mixed episodes and maintenance in bipolar I. Crucially, aripiprazole has the most favorable metabolic profile among atypical antipsychotics—it has minimal effect on weight, lipids, and glucose. Olanzapine and quetiapine both have strong antimanic evidence but carry significantly higher risk for weight gain, dyslipidemia, and new-onset diabetes. Clozapine is reserved for treatment-resistant cases.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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