Cariprazine in bipolar disorder: clinical efficacy, tolerability, and place in therapy

Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist in late-stage clinical development for the treatment of bipolar disorder (manic/mixed and depressive episodes), as well as for schizophrenia, and as an adjunctive agent for the treatment of major depressive disorder. Three phase 2 or 3, 3-week, randomized controlled trials in bipolar mania or mixed episodes have been completed and reported as poster presentations or in press releases by the manufacturer. Superiority over placebo on the Young Mania Rating Scale total score was evidenced for daily doses of cariprazine 3-12 mg/day. In short-term randomized controlled trials, cariprazine does not appear to adversely impact metabolic variables, prolactin, or the electrocardiogram (ECG) QT interval. The most commonly encountered adverse events in the mania trials were extrapyramidal disorder, akathisia, insomnia, vomiting, restlessness, sedation, vision blurred, and pain in extremity in the phase 2 trial where this was presented in a poster, and akathisia, extrapyramidal disorder, tremor, dyspepsia, vomiting, dizziness, diarrhea, somnolence, restlessness, and pyrexia for the phase 3 trial where this was presented in a poster. With the exception of akathisia and extrapyramidal disorder, the differences in incidence versus placebo for these events were generally small. If approved by regulatory authorities, cariprazine would join aripiprazole as the second dopamine receptor partial agonist antipsychotic available for clinical use in persons with bipolar mania or mixed episodes. Cariprazine differs from aripiprazole in terms of dopamine D3 receptor selectivity. Further studies would be helpful to discern the distinguishing features of cariprazine from other antimanic agents.