The efficacy of lumateperone across symptoms of a major depressive episode with mixed features in patients with major depressive disorder and bipolar disorder: Post hoc analyses.

INTRODUCTION: Current treatments for major depressive episodes may not resolve all symptoms, with residual symptoms predicting disease relapse, recurrence, and functional impairment. This post hoc analysis of Study 403 (NCT04285515), a randomized, double-blind, placebo-controlled trial in patients with major depressive disorder (MDD) or bipolar disorder presenting with a major depressive episode with mixed features, evaluated the breadth of efficacy of lumateperone 42 mg across depressive symptoms assessed by Montgomery-Åsberg Depression Rating Scale (MADRS) single item scores.

METHODS: Adults aged 18-75 years who met DSM-5 criteria for MDD or bipolar disorder with depressive episode with mixed features were randomized 1:1 to receive 6-week lumateperone 42 mg or placebo treatment.

RESULTS: Among 383 patients in the modified intent-to-treat population, lumateperone significantly improved 9 out of 10 MADRS items, except Suicidal Thoughts, versus placebo at Day 43, with earliest significant improvements observed from Days 8-15. A significantly higher proportion of patients had reduced symptom severity with lumateperone versus placebo across a range of individual MADRS items. A smaller percentage of patients with moderate-to-severe baseline symptoms (MADRS score ≥4) continued to have item scores ≥4 at end of treatment with lumateperone compared with placebo across all individual MADRS items, except for the Suicidal Thoughts item. Young Mania Rating Scale Total score improved from baseline to Day 43 versus placebo, with fewer patients experiencing mania worsening.

CONCLUSION: Lumateperone 42 mg improved a broad range of depressive symptoms in patients with MDD and bipolar depression with mixed features, supporting its therapeutic potential in these conditions.