Meta-analysis of on-the-road experimental studies of hypnotics: effects of time after intake, dose, and half-life

Abstract

BACKGROUND: The use of hypnotics is prevalent in the general population. Though these drugs have been shown to be effective, their residual effects may cause significant impairment to the user's driving ability. The objective of this meta-analysis is to determine whether there is a residual effect on driving and better evaluate the safety of hypnotics. METHOD: Randomized double-blind placebo-controlled studies were selected that employed a commonly used and valid driving measure to determine the user's driving ability the day after drug administration. The primary outcome measure for the driving task in all included studies was the Standard Deviation of Lateral Position (SDLP). Fixed effects model meta-analyses were performed. RESULTS: Fourteen studies, published from 1984 to 2013 (295 subjects), were included in this meta-analysis. Overall, significant impairment was found when morning testing (i.e., 10-11 h after initiating sleep) was compared to afternoon testing (i.e., 16-17 h after initiating sleep; P = .0001). Twice the standard dose also showed significant impairment (P = .0001) relative to the standard dose. The time of the test, morning versus afternoon, also had an impact on individual drugs. Middle of the night administration (MOTN) of zolpidem and zopiclone caused significant impairment the following morning, though no such impairment was seen with zaleplon. Finally, half-life was also assessed (short: <6 h, intermediate: 6-12 h, long: >12 h) and both intermediate- and long-acting drugs caused significant impairment the morning after bedtime administration, whereas short acting hypnotics did not. CONCLUSIONS: These analyses indicate that the half-life, dose of the hypnotic, as well as time between treatment and driving, as measured by SDLP, all significantly impact the ability to drive a car after taking hypnotic drugs.