Lumateperone improves depression symptoms in bipolar disorder

Treatment with 42-mg lumateperone daily leads to significant improvement in depression symptoms, with no serious safety issues, among patients with major depressive episodes associated with both bipolar I and II disorders, a study has shown.

A team of investigators conducted a phase III randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of lumateperone in patients with bipolar I or II disorder (aged 18–75 years) experiencing a major depressive episode. Participants were randomized to receive either lumateperone 42 mg/day (n=188) or placebo (n=189), administered orally once daily in the evening for 6 weeks.

Efficacy endpoints included change from baseline to day 43 in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale–Bipolar Version severity scale (CGI-BP-S), respectively. Safety outcomes were treatment-emergent adverse events (TEAEs), laboratory parameters, vital signs, extrapyramidal symptoms, and suicidality.

At day 43, lumateperone treatment resulted in significantly greater improvement in MADRS score from baseline (least squares mean difference [MD], –4.6 points; effect size, –0.56) and CGI-BP-S total score (least squares MD, –0.9; effect size, –0.46) compared with placebo. The superiority of lumateperone over placebo in MADRS was noted in both bipolar I and II disorders.

The only TEAEs observed with lumateperone at a clinically meaningful higher rate than placebo were nausea and somnolence, while the incidence of extrapyramidal symptom-related TEAEs was low and comparable to that for placebo. In addition, there were minimal changes in weight, vital signs, or metabolic or endocrine assessments.