In a randomized, placebo-controlled, adaptive dose–finding study conducted in more than 200 patients with MDD, those with more severe insomnia at baseline had a greater improvement in depressive symptoms versus those with less severe insomnia.
“As seltorexant is an orexin receptor antagonist, it is related to other medications that are marketed as sleeping pills, so it was important to show that its antidepressant efficacy was actually caused by improved sleep,” coinvestigator Michael E. Thase, MD, professor of psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, told this news organization.
University of Pennsylvania
Dr. Michael E. Thase
“This novel antidepressant may well turn out to be a treatment of choice for depressed patients with insomnia,” said Dr. Thase, who is also a member of the medical and research staff of the Corporal Michael J. Crescenz Department of Veterans Affairs Medical Center.
The findings were presented at the American Society of Clinical Psychopharmacology annual meeting.
Clinically meaningful?
In an earlier exploratory study, seltorexant showed antidepressant and sleep-promoting effects in patients with MDD. In a phase 2b study, a 20-mg dose of the drug showed clinically meaningful improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score after 6 weeks of treatment.
In the current analysis, the investigators evaluated the effect of seltorexant in improving depressive symptoms beyond sleep-related improvement in patients with MDD, using the MADRS-WOSI (MADRS without the sleep item).
They also used the six-item core MADRS subscale, which excludes sleep, anxiety, and appetite items.
The 283 participants were randomly assigned 3:3:1 to receive seltorexant 10 mg or 20 mg or placebo once daily. They were also stratified into two groups according to the severity of their insomnia: those with a baseline Insomnia Severity Index [ISI] score of 15 or higher (58%) and those with a baseline ISI score of less than 15 (42%).
Results showed that the group receiving the 20-mg/day dose of seltorexant (n = 61 patients) obtained a statistically and clinically meaningful response, compared with the placebo group (n = 137 patients) after removing the insomnia and other “not core items” of the MADRS. The effect was clearest among those with high insomnia ratings.
Improvement in the MADRS-WOSI score was also observed in the seltorexant 20-mg group at week 3 and week 6, compared with the placebo group.
The LSM average distance
The least squares mean (LSM) average difference between the treatment and placebo groups in the MADRS-WOSI score at week 3 was −3.8 (90% confidence interval, −5.98 to −1.57; P = .005).
At week 6, the LSM between the groups in the MADRS-WOSI score was −2.5 (90% CI, −5.24 to 0.15; P = .12).
The results were consistent with improvement in the MADRS total score. At week 3, the LSM in the MADRS total score was -4.5 (90% CI, -6.96 to -2.07; P = .003) and, at week 6, it was -3.1 (90% CI, -6.13 to -0.16; P = .083).
Seltorexant 20 mg was especially effective in patients who had more severe insomnia.
Commenting on the study, Nagy Youssef, MD, PhD, professor of psychiatry, The Ohio State University Wexner Medical Center, Columbus, said this was “a well-designed study examining a promising compound.”
Ohio State University
Dr. Nagy Youssef
“Especially if replicated, this study shows the promise of this molecule for this patient population,” said Dr. Youssef, who was not involved with the research.
The study was funded by Janssen Pharmaceutical of Johnson & Johnson. Dr. Thase reports financial relationships with numerous companies. Dr. Youssef reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.