Seltorexant Reduces Core Depressive Symptoms in Patients With Major Depressive Disorder: Analysis Based on MADRS-WOSI and MADRS-6

Abstract: Objectives: To evaluate seltorexant effect in improving depressive symptoms beyond sleep-related improvement in major depressive disorder (MDD) using MADRS-WOSI (MADRS without sleep item) and MADRS-6 (6 core depression items). Methods: In this phase-2b study (NCT03227224), adults with MDD (DSM-5 criteria; inadequate response to 1-3 SSRIs/SNRIs) were randomized 2:1:1 to placebo/seltorexant-20mg/seltorexant-40mg once-daily. After an interim-analysis, newly recruited patients were randomized 3:3:1 to placebo/seltorexant-10mg/seltorexant-20mg once-daily. Randomization was stratified for patients with (baseline Insomnia Severity Index [ISI] score≥15) vs without clinically significant/subthreshold insomnia symptoms (ISI