Lumateperone Treatment for Major Depressive Episodes With Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder

Abstract: Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder (BD). This randomized, double-blind, placebo-controlled, multicenter trial (NCT04285515) investigated the efficacy and safety of lumateperone 42mg to treat a major depressive episode (MDE) in patients with major depressive disorder (MDD) or BD with mixed features. Methods: Adults with DSM-5 diagnosed MDD or bipolar I or II disorder with mixed features experiencing an MDE (Montgomery-Asberg Depression Rating Scale [MADRS] Total score≥24 and Clinical Global Impression Scale-Severity [CGI-S] score≥4) were randomized 1:1 to lumateperone 42mg or placebo. Primary and key secondary efficacy outcomes were change from baseline to Day 43 in MADRS Total score and CGI-S score, respectively. Safety was assessed. Results: Of 385 patients treated, 344 (89.4%) completed the study and 383 were in the modified intent-to-treat population (placebo, n=191; lumateperone, n=192). MADRS Total score significantly improved with lumateperone 42mg vs placebo in the combined MDD/BD population (mean change from baseline to Day 43 least squares mean difference vs placebo (LSMD)=−5.7; 95% CI, −7.60, −3.84; effect size=−0.64; PShort Description: This randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of lumateperone 42mg for the treatment of a major depressive episode in patients with major depressive disorder with mixed features or bipolar depression with mixed features. Compared with placebo, lumateperone 42mg significantly improved symptoms of depression and disease severity in the combined and individual major depressive disorder and bipolar depression populations. Treatment with lumateperone was generally safe and well tolerated, consistent with prior studies.Name of Sponsoring Organization(s):