Seltorexant, Adjunctive to Antidepressants, in Adults With Major Depressive Disorder With Insomnia Symptoms: Results of a Double-Blind, Randomized, Placebo-Controlled Study
Background: This double-blind, randomized, placebo-controlled phase 3 study (NCT04533529) compared the efficacy and safety of adjunctive seltorexant to placebo in participants with major depressive disorder (MDD) with insomnia symptoms (IS) who had experienced inadequate response to 1-2 SSRI/SNRI.
Methods: Eligible participants were randomized 1:1 to receive seltorexant 20 mg or matching placebo for 6 weeks, while continuing their baseline SSRI/SNRI. The primary efficacy endpoint was change from baseline to day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Key secondary efficacy endpoints were changes from baseline to day 43 in MADRS without sleep item (MADRS-WOSI) total score and Patient Reported Outcome Measurement Information System-Sleep Disturbance 8-item short-form (PROMIS-SD-8a) T-score. Efficacy was analyzed via mixed effects models for repeated measures.
Results: 588 participants with MDD were randomized (seltorexant: n=284 [216 with IS]; placebo: n=304 [228 with IS]), of which 586 received ≥1 dose of study drug (mean age 45.1 years, 77.1% white, 76.6% female). The primary and key secondary efficacy endpoints significantly improved with seltorexant versus placebo at day 43; the least-squares mean difference (95% CI; 2-sided p) in MADRS total score: -2.6 (-4.53, -0.74; p=0.007), MADRS-WOSI total score: -2.0 (-3.75, -0.28; p=0.023), and PROMIS-SD-8a T-score: -3.7 (-5.48, -2.00; p < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 36.0%/40.3% of seltorexant/placebo recipients. One participant in each group experienced non drug-related serious TEAE(s).
Conclusions: Seltorexant showed significant and clinically meaningful antidepressant effects, beyond improvement of insomnia symptoms. Seltorexant demonstrated a safety profile similar to placebo.
