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

• Published in: European neuropsychopharmacology 2024-04, Vol.81, p.53-63
• 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: Article
• Language: English
• Subjects: Driving performance; Hypnotic; Safety; Sleep drugs
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2024.01.011

•Sleep medications often carry residual effects potentially affecting driving safety.•Considering the vehicle's standard deviation of lateral position, most molecules paralleled the placebo, outperforming zopiclone.•Repeated administration caused fewer residual effects compared to acute one, except for flurazepam.•Repeated administration reduced residual effects. 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.