Lumateperone in the Treatment of Major Depressive Disorder and Bipolar Depression With Mixed Features: Efficacy Across Symptoms
Introduction: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or II disorder. This prospectively defined analysis of a randomized, double-blind, placebo-controlled trial (Study 403; NCT04285515) evaluated lumateperone efficacy on individual depressive symptoms by Montgomery-Åsberg Depression Rating Scale (MADRS) single-item scores in patients with depressive episodes associated with major depressive disorder (MDD) or bipolar depression with mixed features.
Methods: Adults (18-75 years) with DSM-5–defined MDD or bipolar I or II disorder experiencing a major depressive episode (MADRS Total score≥24, Clinical Global Impression Scale-Severity score≥4) with mixed features were randomized 1:1 to 6-week lumateperone 42mg or placebo. MADRS single-item scores were evaluated by-visit. Safety was assessed.
Results: Lumateperone significantly improved MADRS Total score vs placebo at Day 43 (placebo, n=191; lumateperone, n=192; least squares mean difference vs placebo [LSMD]=−5.7; P < .0001). The lumateperone group showed significantly greater improvements (P < .01) on 9 of 10 MADRS items vs the placebo group on Day 43: apparent sadness (LSMD=−0.9), reported sadness (LSMD=−0.8), inner tension (LSMD=−0.6), reduced sleep (LSMD=−0.9), reduced appetite (LSMD=−0.5), concentration difficulties (LSMD=−0.4), lassitude (LSMD=−0.6), inability to feel (LSMD=−0.7), and pessimistic thoughts (LSMD=−0.4). Apparent sadness and reduced sleep had the largest improvements with lumateperone vs placebo at Day 43 and the earliest significant reductions (Day 8; P < .05). Lumateperone was well-tolerated and there was no worsening in Young Mania Rating Scale Total score.
Conclusion: Lumateperone 42mg significantly improved a broad range of depression symptoms compared with placebo in depressed patients with mixed features associated with MDD or bipolar depression.
