The efficacy and safety of dual orexin receptor antagonists in obstructive sleep apnea: A systematic review and meta‐analysis of randomised controlled trials

Summary Dual orexin receptor antagonists (DORAs) are indicated for the treatment of insomnia disorder. However, DORAs may change sleep parameters, thus having adverse effects on patients with obstructive sleep apnea (OSA). This meta‐analysis clarified the impact of DORAs in OSA treatment on sleep architecture and respiratory parameters. We systematically searched PubMed, Embase, and Cochrane Central databases for randomised control trials published up to May 2024. The search focussed on studies discussing the effects of DORAs on sleep architecture in patients with OSA. Nonrandomised studies were excluded. A meta‐analysis using a random‐effects model was performed. The patients were categorised into subgroups based on the treatment protocol (single or multiple dosages). The Cochrane risk of bias tool for randomised trials assessed the risk of bias. Our meta‐analysis included four randomised placebo‐controlled trials, encompassing 126 patients with a mean age of 49.1 years. The effects of DORAs on sleep architecture and respiratory parameters were examined. The main findings were as follows: DORAs significantly increased the total sleep time and improved sleep efficiency. However, they did not affect rapid eye movement sleep. DORAs also showed a trend towards decreased wake after sleep onset and did not increase the apnea–hypopnea index. DORAs did not increase the percentage of total sleep time with oxygen saturation lower than 90% and 85% compared with placebo, respectively. Furthermore, DORAs were not associated with significantly higher adverse effects compared with placebo. This meta‐analysis demonstrated that DORAs improve sleep and do not impair nighttime respiratory function in patients with OSA.