Lumateperone was found, in a phase 3, randomized, double-blind, placebo-controlled trial, to improve depressive symptoms among patients with bipolar I and II disorders (BD) with major depressive episodes. These findings were published in the American Journal of Psychiatry.
Patients (N=377) with BD and a depression score of ≥20 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and ≥4 on the depression and bipolar illness subscales of the Clinical Global Impressions Scale-Bipolar Version severity scale (CGI-BP-S) were recruited from 54 sites in 6 countries. After a 2-week treatment discontinuation, patients were stratified by BD I and II and randomly assigned in a 1:1 ratio to receive 42 mg/day lumateperone (n=188) or placebo (n=189) for 6 weeks. Response to treatment was defined as a ≥50% decrease in MADRS score and remission as a MADRS score of ≤12 points.
The treatment and control cohorts were aged mean 46 (SD, 14.1) and 44 (SD, 12.9) years, 47.3% and 36.5% were men, 92.0% and 90.5% were White, 79.8% and 79.9% had BD I, and 88.3% and 88.9% experienced 1 to 9 depressive episodes in their lifetime, respectively.
At day 43, lumateperone was associated with a greater MADRS score decrease compared with placebo (least squares mean difference [LSMD], -4.6; 95% CI, -6.34 to -2.83; P <.0001). The improvement to MADRS was observed among the intervention cohort as early as day 8 and continuing thereafter.
Among the lumateperone and placebo cohorts, the response rates were 51.1% and 36.7% (P <.001) and remission rates were 39.9% and 33.5% (P =.018), respectively.
A greater decrease in CGI-BP-S total score was observed among the lumateperone recipients (LSMD, -1.0; 95% CI, -1.46 to -0.61; P <.001) and for the depression (LSMD, -0.5; 95% CI, -0.75 to -0.30; P <.0001) and overall bipolar illness (LSMD, -0.4; 95% CI, -0.65 to -0.22; P <.0001) subscores.
Quality of Life Enjoyment and Satisfaction Questionnaire–Short Form (Q-LES-Q-SF) scores more greatly increased among the lumateperone cohort (LSMD, 4.6; 95% CI, 1.42-7.69; P =.005).
Stratified by BD type, both BD I (LSMD, -4.0; 95% CI, -5.92 to -1.99; P <.0001) and BD II (LSMD, -7.0; 95% CI, -10.92 to -3.16; P <.001) exhibited greater decreases in MADRS scores among the treatment group compared with placebo.
Treatment-emergent adverse events were reported by 54.8% of lumateperone and 50.3% of placebo recipients. More treatment recipients had drug-related treatment-emergent adverse events (41.5% vs 31.2%). The treatment-emergent adverse events which occurred among >5% of lumateperone recipients were somnolence (8.5% vs 1.1%) and nausea (6.4% vs 2.1%) compared with placebo, respectively. Discontinuation due to adverse events occurred among 11 of the lumateperone and 4 of the placebo cohorts.
This study may not be generalizable to the overall BD population, as patients with treatment-resistant illness, imminent suicidal risk, rapid cycling disease, or serious psychiatric comorbidities were excluded.
This study found that lumateperone was well-tolerated and significantly improved depression symptoms among patients with BD who were experiencing a depressive episode.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Calabrese JR, Durgam S, Satlin A, et al. Efficacy and safety of lumateperone for major depressive episodes associated with bipolar I or bipolar II disorder: a phase 3 randomized placebo-controlled trial. Am J Psychiatry. 2021;178(12):1098-1106. doi:10.1176/appi.ajp.2021.20091339