Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics

• Published in: European neuropsychopharmacology Vol. 81; p. 53
• Main Authors: Fornaro, Michele, Caiazza, Claudio, Rossano, Flavia, Cilmi, Flavia, De Prisco, Michele, Vieta, Eduard, Thompson, Trevor, Solmi, Marco, Carvalho, Andre Ferrer, Iasevoli, Felice, de Bartolomeis, Andrea
• Format: Journal Article
• Language: English
• Published: Netherlands 01.04.2024
• Subjects: Automobile Driving; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - therapeutic use; Psychomotor Performance - drug effects; Randomized Controlled Trials as Topic - methods; Sleep Initiation and Maintenance Disorders - drug therapy; Sleep Wake Disorders - drug therapy; Hypnotic; Sleep drugs; Safety; Driving performance
• ISSN: 1873-7862; 1873-7862
• DOI: 10.1016/j.euroneuro.2024.01.011

Sleep medications often carry residual effects potentially affecting driving safety, warranting network meta-analysis (NMA). PubMed/EMBASE/TRID/Clinicaltrials.gov/WHO-ICTRP/WebOfScience were inquired for randomized controlled trials of hypnotic driving studies in persons with insomnia and healthy subjects up to 05/28/2023, considering the vehicle's standard deviation of lateral position - SDLP (Standardized Mean Difference/SMD) and driving impairment rates on the first morning (co-primary outcomes) and endpoint. Risk-of-bias, global/local inconsistencies were measured, and CINeMA was used to assess the confidence in the evidence. Of 4,805 identified records, 26 cross-over RCTs were included in the systematic review, of which 22 entered the NMA, focusing on healthy subjects only. After a single administration, most molecules paralleled the placebo, outperforming zopiclone regarding SDLP. In contrast, ramelteon 8 mg, daridorexant 100 mg, zolpidem 10 mg bedtime, zolpidem middle-of-the-night 10 mg and 20 mg, mirtazapine 15-30 mg, and triazolam 0.5 mg performed significantly worse than placebo. Lemborexant 2.5-5 mg, suvorexant 15-20 mg, and zolpidem 3.5 mg middle-of-the-night associated with lower impairment than zopiclone. Repeated administration (maximum follow-up time of ten days) caused fewer residual effects than acute ones, except for flurazepam. Heterogeneity and inconsistency were negligible. Confidence in the evidence was low/very low. Sensitivity analyses confirmed the main analyses. Most FDA-approved hypnotics overlapped placebo at in-label doses, outperforming zopiclone. Repeated administration for 15 days or less reduced residual effects, warranting further research on the matter.