Dose-response meta-analysis of dual orexin receptor antagonists on sleep parameters and implications for orexin-mediated arousal.
Sleep MedSep 7, 2026 (epub)
Clinical ResearchPsychiatry
Claudio Caiazza, Laura Palagini, Claudia Toni et al.
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In 30 seconds
This meta-analysis evaluated the dose-response effects of dual orexin receptor antagonists (DORAs) on sleep parameters in adults with insomnia disorder. Analyzing 21 randomized placebo-controlled trials, the study found that DORAs improved sleep-continuity outcomes, with effects plateauing within approved dose ranges, indicating limited benefits from higher doses.
Key findings
- DORAs improved total sleep time and sleep efficiency with dose-related effects.
- Effects often plateaued within or near approved dose ranges, indicating limited benefits from higher doses.
- Lemborexant showed lower attenuation in sleep-continuity outcomes after repeated use.
- Sleep-architecture analyses indicated modest drug-specific changes in sleep stages.
Why it matters
Understanding the dose-response relationship of DORAs is crucial for optimizing treatment strategies in insomnia disorder, as it informs clinicians about the efficacy and potential limitations of higher dosing.