TOPLINE:

Seltorexant, a selective orexin-2 receptor antagonist, was associated with greater improvement in initiation and maintenance of sleep in adults with insomnia than both placebo and zolpidem, a standard insomnia treatment, showed a new study. Treatment-emergent adverse events (TEAEs) were also significantly lower for participants receiving seltorexant than those receiving either placebo or zolpidem.

METHODOLOGY:

• The randomized, double-blind, placebo- and active-controlled dose-finding trial was conducted from 2017 to 2019 at 55 sites across six countries.
• It included more than 300 adults aged 18-85 years with insomnia (Insomnia Severity Index score ≥ 15) and no psychiatric comorbidity. Their mean age was 58 years; 68% were women and 69% were White individuals.
• Participants were randomly assigned to receive nightly for 14 days oral seltorexant at a dose of 5 mg (n = 71), 10 mg (n = 74), or 20 mg (n = 71); placebo (n = 75); or zolpidem (5 or 10 mg, n = 73).
• The primary outcome was initiation of continuous sleep, known as “latency to persistent sleep (LPS),” measured with polysomnography on night 1. Secondary outcomes included wake after sleep onset over the first 6 hours (WASO-6) on nights 1 and 13 and LPS at night 13. TEAEs were monitored throughout the trial.

TAKEAWAY:

• Seltorexant at 10 mg and 20 mg showed greater improvement for night 1 LPS than placebo (by 36% and 49%, respectively), and the 20 mg dose showed greater improvement than zolpidem (by 29%).
• Night 1 WASO-6 was also improved for 10 mg and 20 mg seltorexant compared with placebo (by 32% and 40%, respectively). However, it was comparable between zolpidem and the three seltorexant dose groups.
• LPS at night 13 showed 30% and 28% improvements for 10 mg and 20 mg seltorexant, respectively, vs zolpidem. WASO-6 at night 13 had improvements of 25% and 40% for 10 mg and 20 mg seltorexant, respectively, vs placebo; and the 20 mg dose showed 31% improvement vs zolpidem.
• TEAEs were lower in the combined seltorexant groups (34%) than placebo group (49%) and zolpidem group (43%). Headache was the most common AE (8% for seltorexant vs 11% for placebo and for zolpidem).

IN PRACTICE:

“These data indicate that 10 mg and 20 mg of seltorexant are efficacious doses for participants with insomnia. Seltorexant, up to 20 mg, appeared to be generally better tolerated than zolpidem (5-10 mg) in both adult and older adult populations,” the investigators wrote.

SOURCE:

This study was led by Sofie Mesens, MD, Johnson & Johnson, Beerse, Belgium. It was published online on August 13 in JAMA Psychiatry.

LIMITATIONS:

This study was limited to a subpopulation of individuals with insomnia who did not have psychiatric comorbidities. Additionally, < 3% of participants were women of childbearing age, who represent a major proportion of patients with insomnia. 

DISCLOSURES:

This study was funded by Johnson & Johnson. Several investigators reported having ties with various sources, including Johnson & Johnson. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.