Zopiclone as Positive Control in Studies Examining the Residual Effects of Hypnotic Drugs on Driving Ability

Joris      C. Verster; D.      Warren Spence; Azmeh      Shahid; Seithikurippu      R. Pandi-Perumal; Thomas      Roth

Abstract

Zopiclone (7.5 mg) is frequently used as a positive control in studies that examine the residual effects of hypnotic drugs on driving ability and related skills. This review summarizes studies examining the effects of zopiclone, and discusses its usefulness as a comparator drug for investigations of residual effects of novel sleep medication. A literature review (Pubmed and Embase) was conducted searching for studies that tested zopiclone on driving. Cross references were checked for additional papers.

Eight studies utilizing the standardized on-the-road driving test consistently showed that in the morning following bedtime administration zopiclone (7.5 mg) significantly impaired driving performance. A total of 191 healthy volunteers were tested after placebo and zopiclone (7.5 mg). Meta analyses showed no significant differences in driving performance after zopiclone (7.5 mg) between adult and elderly healthy volunteers. The combined effect size (ES) and 95% confidence interval (95%CI) for healthy volunteers was 0.782 (0.620, 0.944). Relative to placebo, an average increment of 3.0 cm in Standard Deviation of Lateral Position (SDLP) was observed when treated with zopiclone (7.5 mg). This deviation was higher than the increment in SDLP reported for drivers with a blood alcohol concentration of 0.05% (+2.4 cm). Results from driving simulators and psychometric tests are consistent with the on-road driving test results.

In conclusion, zopiclone (7.5 mg) is a reliable positive control, that consistently shows significant and meaningful impairment on the on-the-road driving test.

Keywords: zopiclone, driving, SDLP, comparator, active control, clinical trials, Hypnotic Drugs, Non-benzodiazepine Alternatives, Digit Symbol Substitution Test, Critical Flicker Fusion Test