Treatment of chronic insomnia in elderly adults with dual orexin receptor antagonists: a systematic review and meta-analysis

Study Objectives Chronic insomnia is common among older adults, and its management is particularly challenging due to changes in sleep architecture, multimorbidity, and increased vulnerability to adverse drug effects. Dual orexin receptor antagonists have emerged as a novel therapeutic class with promising efficacy and tolerability profiles. However, evidence specific to older adults remains limited. Here, we performed the first systematic review and meta-analysis specifically evaluating the efficacy and safety of dual orexin receptor antagonists in elderly patients with chronic insomnia (PROSPERO CRD42024565687).Methods Randomized controlled trials were identified from MEDLINE, Scopus, and ClinicalTrials.gov. Objective polysomnographic outcomes, including latency to persistent sleep, total sleep time, and wake after sleep onset, as well as subjective sleep measures, were analyzed, along with safety outcomes.Results Ten studies met the inclusion criteria for the systematic review, with five studies contributing to the meta-analysis. The quantitative synthesis comprised 2235 patients in the experimental group and 1409 patients in the control group. Overall, compared with placebo dual orexin receptor antagonists reduced wake after sleep onset and latency to persistent sleep while increasing total sleep time after 1 month and 3 months of treatment. Importantly, dual orexin receptor antagonists increased subjective total sleep time. Finally, daridorexant showed a favorable safety profile, whereas lemborexant and suvorexant were associated with higher rates of treatment-emergent adverse events than placebo, without an increase in serious adverse events.Conclusions Despite limited evidence, dual orexin receptor antagonists appear effective and generally safe for treating chronic insomnia in the elderly, supporting their role as a valuable therapeutic option.