The effects of different dosages of dual orexin receptor antagonists and zolpidem on sleep and cognitive function: A meta-analysis and systematic review

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ObjectiveWe aimed to compare the efficacy and safety profiles of different dosages of dual orexin receptor antagonists (DORAs) and zolpidem on insomnia and cognitive function. MethodsDatabases including PubMed, Embase, Cochrane Library, Scopus, and Google Scholar were searched for relevant articles. The standard mean difference (SMD) was generated for consecutive variants. A dose‒response meta-regression model was constructed in RStudio 4.2.1 to compare the efficacy and safety of low, medium and high doses of DORAs and zolpidem on cognitive function and insomnia. ResultsA total of 22 studies with 8,223 subjects were included. Compared with the placebo, low and medium doses of DORAs significantly decreased motor vehicle accidents/violations (SMD= -0.02, 95 % CI: -0.21 to 0.17 and SMD= -0.36, 95 % CI: -0.52 to -0.20, respectively), whereas medium and high doses of zolpidem significantly increased this index (SMD=0.77, 95 % CI: 0.39 to 1.16 and SMD=1.17, 95 % CI: 0.62 to 1.72, respectively). In addition, the total sleep time (TST) of low, medium, and high doses of DORAs was SMD=0.28, 95 % CI: - 0.15 to 0.70; SMD=1.36, 95 % CI: 0.87 to 1.86; and SMD=2.59, 95 % CI: 1.89 to 3.30, respectively. The TST of zolpidem at low, medium, and high doses was SMD=1.01, 95 % CI: 0.18 to 1.83; SMD=1.94, 95 % CI: 0.46 to 3.43; and SMD=1.71, 95 % CI: 0.86 to 2.56, respectively. ConclusionWe recommend DORAs as the best intervention for insomnia. DORAs were highly effective in inducing and maintaining sleep without impairing cognition. More head-to-head studies are needed to extend and consolidate our findings.