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

Objective: We aimed to compare the efficacy and safety profiles of different dosages of dual orexin receptor antagonists (DORAs) and zolpidem on insomnia and cognitive function. Methods: Databases 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. Results: A 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. Conclusion: We 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.