Psychopharmacology (2011) 215:321–332 which influence exposure to these drugs need to be taken into account. Especially if there is a dose–response relation- ship between car driving performance and dose of the drug, then factors which increase exposure (e.g., gender, race, age, or P450 polymorphism) are likely to display more pronounced car driving impairment, which may reach levels of clinical relevance. Consequently, it should be recommended to always take factors likely to affect drug exposure and response, such as cytochrome P450 polymorphism into account when designing future studies on drug effects on driving. In the present study, single doses of zopiclone 7.5 mg increased SDLP by 2.6 cm over placebo. Mean difference in SDLP with placebo and its 95% CI upper limit exceeded the non-inferiority margin of 2.5 cm and the CI excluded zero. These data support findings from a number of previous studies that assessed the influence of zopiclone 7.5 mg on SDLP as measured in the standardized highway driving test (Leufkens et al. 2009; Leufkens and Vermeeren 2009; Vermeeren 2004). All of these studies demonstrated that evening doses of zopiclone produced residual driving impairment in the morning. In all studies, the impairing effects of zopiclone 7.5 mg were comparable to a BAC between 0.5 and 0.8 mg/ml. In the present study, impairment after zopiclone (verum) confirmed the sensitivity of the highway driving test for sedative drug effects and confirmed previous warnings concerning driving (Leufkens et al. 2009; Leufkens and Vermeeren 2009; Vermeeren 2004). Overall, low doses of esmirtazapine (1.5 mg) did not produce any relevant driving impairment after single and repeated dosing. Driving impairment did occur after a higher single dose of emirtazapine (4.5 mg) but resolved after repeated doses. 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