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Purpose <p>Sedative-hypnotics for insomnia carry risks of adverse effects and dependence. We reviewed how lemborexant, a dual orexin receptor antagonist (DORA), compares with sedative-hypnotics (benzodiazepines and z-drugs) in adults with insomnia across sleep, adverse events, dependence, and switching.</p> Methods <p>We conducted a PRISMA-guided systematic narrative review (not a meta-analysis; not prospectively registered), searching PubMed, Google Scholar, Embase, Cochrane CENTRAL, and PsycINFO from January 2000 (last searched 10 June 2026). Two reviewers independently screened and extracted data; risk of bias was assessed with Cochrane RoB 2 and ROBINS-I and certainty with GRADE, and synthesis followed SWiM.</p> Results <p>Sixteen reports (12 unique studies) were included. The only head-to-head efficacy comparator was zolpidem; no trial has compared lemborexant with a benzodiazepine or a non-zolpidem agent for insomnia efficacy. Against zolpidem, lemborexant improved objective polysomnographic sleep onset, maintenance, and efficiency (moderate certainty), although subjective sleep maintenance was mixed (zolpidem was superior on diary-reported wake after sleep onset at one month). At therapeutic doses it caused less next-day postural instability (moderate certainty), psychomotor/cognitive separation was clearest versus supratherapeutic zolpidem (low certainty). Falls and switching signals were of very low certainty, and abuse potential did not differ significantly from zolpidem (not lower).</p> Conclusion <p>Lemborexant is a promising alternative to zolpidem, with a favourable objective-sleep and next-day-safety profile (in older adults), but evidence against the broader sedative-hypnotic class is absent and most safety and switching signals are of low certainty; broader, long-term, head-to-head trials against benzodiazepines and other agents are needed.</p>

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Lemborexant Versus Sedative-Hypnotics in the Treatment of Insomnia: A Systematic Narrative Review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Benjamin Holloway,
  • Jake Sandrini

摘要

Purpose

Sedative-hypnotics for insomnia carry risks of adverse effects and dependence. We reviewed how lemborexant, a dual orexin receptor antagonist (DORA), compares with sedative-hypnotics (benzodiazepines and z-drugs) in adults with insomnia across sleep, adverse events, dependence, and switching.

Methods

We conducted a PRISMA-guided systematic narrative review (not a meta-analysis; not prospectively registered), searching PubMed, Google Scholar, Embase, Cochrane CENTRAL, and PsycINFO from January 2000 (last searched 10 June 2026). Two reviewers independently screened and extracted data; risk of bias was assessed with Cochrane RoB 2 and ROBINS-I and certainty with GRADE, and synthesis followed SWiM.

Results

Sixteen reports (12 unique studies) were included. The only head-to-head efficacy comparator was zolpidem; no trial has compared lemborexant with a benzodiazepine or a non-zolpidem agent for insomnia efficacy. Against zolpidem, lemborexant improved objective polysomnographic sleep onset, maintenance, and efficiency (moderate certainty), although subjective sleep maintenance was mixed (zolpidem was superior on diary-reported wake after sleep onset at one month). At therapeutic doses it caused less next-day postural instability (moderate certainty), psychomotor/cognitive separation was clearest versus supratherapeutic zolpidem (low certainty). Falls and switching signals were of very low certainty, and abuse potential did not differ significantly from zolpidem (not lower).

Conclusion

Lemborexant is a promising alternative to zolpidem, with a favourable objective-sleep and next-day-safety profile (in older adults), but evidence against the broader sedative-hypnotic class is absent and most safety and switching signals are of low certainty; broader, long-term, head-to-head trials against benzodiazepines and other agents are needed.