The pharmaceutical therapies for insomnia that are now available have a number of drawbacks. Thus, this research was set to evaluate the new selective orexin-2 receptor antagonist seltorexant's effective dosage range, safety, and tolerability in treating insomnia condition.
This placebo-controlled polysomnography trial was carried out at 55 locations across 6 countries between November 2017 and April 2019 and was examined in August 2019. The people (ages 18–64) and older people (ages 65–85) without psychiatric comorbidities who had insomnia (insomnia severity index score ≥15) were included. For 14 days, participants were randomized 1:1:1:1:1 to receive zolpidem (5–10 mg), a placebo, or oral seltorexant (5–20 mg) per night.
A total of 364 individuals (mean age 57.8 years; 67.6% female) were randomly assigned to receive zolpidem (n=73), seltorexant 5 mg (n=71), 10 mg (n=74), or 20 mg (n=71), a placebo (n=75), or both. Seltorexant showed a substantial dose-response impact on latency to persistent sleep (LPS) on the first night.
It was superior to zolpidem at 20 mg and showed notable improvements at 10 and 20 mg when compared to placebo. At these dosages, there was also a substantial improvement in wake after sleep onset over 6 hours (WASO-6). The benefits of seltorexant in LPS and WASO-6 persisted until night 13, although zolpidem's decreased.
Seltorexant 10 mg and 20 mg increased LPS by 30% and 28%, respectively, as compared to zolpidem at night 13, while 20 mg decreased WASO-6 by 31%. Seltorexant caused fewer treatment-emergent adverse events (TEAEs) (33.8%) than either zolpidem (42.5%) or a placebo (49.3%). In seltorexant groups, there were two severe TEAEs and a couple asymptomatic TEAEs linked to ECG that resulted in cessation.
Overall, seltorexant showed promise in initiating and maintaining sleep in adults and older people with insomnia who did not have mental comorbidities in this study at doses of 10 mg and 20 mg. The effectiveness of zolpidem decreased over the 14-day treatment period, but seltorexant at doses of 10 and 20 mg remained effective.
Source:
Mesens, S., Krystal, A. D., Melkote, R., Xu, H., Pandina, G., Saoud, J. B., Luthringer, R., Savitz, A., & Drevets, W. C. (2025). Efficacy and safety of seltorexant in insomnia disorder: A randomized clinical trial. JAMA Psychiatry (Chicago, Ill.). https://doi.org/10.1001/jamapsychiatry.2025.1999
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