Lumateperone in the Treatment of Patients With Major Depressive Disorder and Bipolar Disorder With Anxious Distress and Mixed Features

Abstract: Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder (BD). This post hoc analysis of a randomized, double-blind, placebo-controlled trial (Study 403; NCT04285515) investigated lumateperone efficacy in patients with major depressive disorder (MDD) or BD with mixed features and anxious distress. Methods: Adults (18-75 years) with DSM-5 MDD or bipolar I or II disorder with mixed features experiencing a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] Total score≥24, Clinical Global Impression Scale-Severity [CGI-S] score≥4) were randomized 1:1 to 6-week lumateperone 42mg or placebo. Patients with DSM-5 mixed features and DSM-5 anxious distress were evaluated in 3 populations: combined MDD/BD, MDD, and BD. Assessments included change in MADRS Total score, CGI-S score, and MADRS inner tension item score. Results: Of 383 patients in the combined MDD/BD population with mixed features, 244 (placebo, 121; lumateperone, 123) had anxious distress. Lumateperone significantly improved change from baseline vs placebo for MADRS Total score at Day 43 in all populations with anxious distress: combined MDD/BD (least squares mean difference vs placebo [LSMD]=−6.1; 95%CI −8.52, −3.71; effect size [ES]=−0.67; PShort Description: This post hoc analysis of a randomized, double-blind, placebo-controlled trial investigated the efficacy of lumateperone in patients with major depressive disorder (MDD) or bipolar depression (BD) with DSM-5 mixed features and DSM-5 anxious distress. Compared with placebo, lumateperone significantly improved symptoms of major depression, global disease severity, and inner tension in the combined MDD/BD population as well as in individual MDD and individual BD populations with mixed features and anxious distress.Name of Sponsoring Organization(s):