A randomized, adaptive dose-finding, placebo-controlled study depicted that people with more severe insomnia at baseline exhibited better amelioration in depressive symptoms with seltorexant use compared to those with less severe insomnia. Utilizing Montgomery-Asberg Depression Rating Scale-Without Sleep Item (MADRS-WOSI), Fran Lowry et al. aimed to assess the impact of seltorexant (orexin receptor antagonist) to mitigate depressive symptoms beyond sleep-related enhancement in people with major depressive disorder.

Overall, 283 subjects were randomly segregated (3:3:1) to get 10 mg or 20 mg seltorexant or placebo once a day. Based on severity of insomnia, stratification of the subjects was done: (i) Subjects with a baseline Insomnia Severity Index score of less than 15 (42%), and (ii) Subjects with a baseline Insomnia Severity Index score of 15 or higher (58%). Also, the six-item core MADRS subscale that excluded sleep, anxiety, and appetite items was used.

Compared to the placebo group (n = 137 patients), the group receiving seltorexant (20 mg/day, n = 61) attained a clinically and statistically meaningful response following the removal of insomnia and other "not core items" of MADRS. Among those with high insomnia ratings, the impact was clearest. In comparison with the placebo group, betterment in the MADRS-WOSI score was also witnessed in the 20-mg seltorexant group at weeks 3 and 6.

The least squares mean (LSM) average difference between the study groups in the MADRS-WOSI score at week 3 and week 6 was −3.8 and −2.5 respectively. The findings were consistent with improvements in MADRS total score. At week 3 and week 6, the LSM in the MADRS total score was -4.5 and -3.1 respectively. Hence, the novel anti-depressant seltorexant appears to be valuable for people suffering from sleep disturbance and concomitant major depressive disorder.