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Seltorexant shows antidepressant effect in MDD

Treatment with seltorexant improved depressive symptoms compared with placebo and the antidepressant efficacy was maintained for a month, according to be exploratory findings published in Translational Psychiatry.

“Despite promising preclinical evidence for a role of orexin-receptor antagonists in the treatment of depressive symptoms, at present clinical evidence is scarce,” Kasper Recourt, MS, from the Center for Human Drug Research, The Netherlands, and colleagues wrote. “The dual orexin1/2 (DORA) antagonist suvorexant is an approved treatment for insomnia, but not for MDD.”

In a phase 1b study, researchers examined the antidepressant effect and the effects of night-time arousal suppression on depressive symptoms in patients with major depressive disorder who received seltorexant.

Overall, 47 patients with MDD were randomized in a 2:1:1 ratio to receive daily seltorexant 20 mg, diphenhydramine 25 mg or placebo at bedtime for 28 days Recourt and colleagues evaluated depressive symptoms using the 17-item Hamilton Depression Rating Scale (HDRS) and the effects on sleep using polysomnography and the Leeds Sleep Evaluation Questionnaire (LSEQ). They also monitored vital signs, suicidal ideation and adverse events to determine the safety and tolerability of seltorexant.

Compared to placebo and diphenhydramine, treatment with seltorexant lead to a greater reduction in core depressive symptoms on average (mean reduction in HDRS = –3.6 and –4.1 vs. –5.5). In addition, the observed antidepressant effects of seltorexant were unrelated to its effect on sleep, according to the results.

Recourt and colleagues also reported that the significant efficacy of seltorexant compared with placebo and diphenhydramine for core depressive symptoms remained up to day 29.

The results showed that the antidepressant efficacy of seltorexant vs. placebo corresponded to an overall increase in EEG power as well as a relative increase in delta-power and decrease in theta-, alpha- and beta power during stage 2 sleep.

The investigators also reported that treatment with seltorexant was safe and well-tolerated. The most commonly occurring adverse events included somnolence, fatigue headache, dizziness, abdominal discomfort and nightmares, and no serious adverse events occurred among those receiving seltorexant. Suicidal ideation scores either improved or were maintained from screening through the end of study, the results showed.

“Overall, treatment with seltorexant showed antidepressant effects on core depressive symptoms as well as a trend towards improving patients’ self-reported sleep experience,” Recourt and colleagues wrote. “This antidepressant effect with onset as early as day 11 of exposure of 20 mg seltorexant versus placebo and diphenhydramine in a relatively small number of patients with MDD warrants study in a larger sample of MDD patients.” – by Savannah Demko

Disclosure: Recourt reports no relevant financial disclosures.