Adjunctive Treatment With Seltorexant Improved Patient-Reported Depressive Symptoms, Insomnia Symptoms, and Overall Health in Major Depressive Disorder With Insomnia

Background: We report secondary/exploratory endpoints assessing patient-reported depressive symptoms, insomnia symptoms, and health-related quality of life (HRQoL) from a phase 3, double-blind, randomized, placebo-controlled study (NCT04533529) of adjunctive orexin-2 receptor antagonist seltorexant in adults with major depressive disorder with insomnia symptoms (MDDIS) and inadequate response to 1-2 SSRI/SNRI.

Methods: Eligible participants were randomized 1:1 to receive seltorexant 20mg or placebo, plus existing SSRI/SNRI, for 6 weeks. Patient Health Questionaire-9 (PHQ-9) total score and Patient Global Impression of Change (PGI-C) assessed patient-reported depressive symptoms; Patient Global Impression of Severity (PGI-S) and European Quality of Life Group, 5-Dimension, 5-Level EQ visual analog scale (EQ-VAS) assessed patient-reported insomnia symptoms and HRQoL, respectively. Analyses used mixed effects models for repeated measures (PHQ-9, PGI-C, PGI-S) or analysis of covariance (EQ-VAS). A least-squares (LS) mean difference 95% confidence interval (CI) that does not include 0 suggests a potential treatment effect.

Results: The LS mean difference (95% CI) in the change in PHQ-9 total, PGI-S “difficulty falling/staying asleep”, PGI-S “not feeling rested the next day”, and EQ-VAS scores from baseline to day 43 between the seltorexant (n=209) and placebo (n=210) groups was -2.1 (-3.30; -0.93), -0.4 (-0.57, -0.14), -0.2 (-0.44, -0.04), and 4.8 (1.48; 8.17), respectively. The LS mean difference (95% CI) in PGI-C score at day 43 between seltorexant and placebo groups was -0.3 (-0.60, -0.09).

Conclusions: From the patient’s perspective, adjunctive treatment with seltorexant improved depressive symptoms, insomnia symptoms, and HRQoL, compared to placebo, in adults with MDDIS and an inadequate response to SSRI/SNRI.