The Effect of Dual Orexin Receptor Antagonists on Next-Day Driving: A Systematic Review and Meta-Analysis

Residual sedation from hypnotic drugs is a causal factor for many motor vehicle accidents. The objective of this systematic literature review and meta-analysis was to assess the impact of currently available DORAs on next-day driving by including daridorexant, which was approved by the US FDA and EMA in early 2023. Six on-the-road (OTR) and simulator driving studies were identified for lemborexant, suvorexant, daridorexant, and for zopiclone. Pairwise random-effects meta-analyses were performed to assess the mean difference in standard deviation of lateral position (∆SDLP) between each treatment and placebo. Clinical relevance was concluded if ≥2.4 cm difference was seen in SDLP between active intervention and placebo for the OTR tests. No validated SDLP threshold has been established for simulator tests. After first administration of the insomnia treatment, ∆SDLP between placebo and lemborexant 5 mg or 10 mg was not statistically significant or clinically relevant. In elderly, SUV 15 mg did not impair driving. However, in adults SUV 20 mg did statistically impair driving, but without clinical relevance. ∆SDLP for daridorexant 50 mg was statistically significant after single dosing. After repeated dosing, SDLP for all DORAs were not statistically different from placebo. Zopiclone 7.5 mg significantly impaired driving after the first administration, validating the sensitivity of the driving tests. Patients should be informed about the possible impact of DORAs on driving, particularly after treatment initiation.