Next-morning driving performance after middle-of-the-night administration of hypnotic drugs: Evidence from dutch on-road driving studies

Introduction: Sleep maintenance problems are common, hence treatments enabling people to more rapidly fall asleep after middle-of-thenight (MOTN) awakenings, without impairing next morning alertness, are needed. The current literature review compared the effects of MOTN administration on morning driving ability, i.e. a potentially dangerous daily activity that can be impaired. Methods: A literature search was conducted identifying on-the-road driving studies examining the effects of MOTN administration of hypnotics on morning driving performance. In a standardized 100-km highway driving test in normal trafic, subjects were instructed to drive with a steady lateral position and constant speed of 95 km/h. Primary outcome measure of the driving test was the Standard Deviation of Lateral Position (SDLP, cm), i.e. the weaving of the car. Results: Four on-road driving studies were identiied. Driving performance after MOTN administration of traditional benzodiazepine hypnotics was not examined. Zolpidem (10 mg and 20 mg, oral immediate release tablets) signiicantly impaired on-road driving in a dose-dependent manner, when tested 4 hours after MOTN administration. Also, gaboxadol (15 mg) and zopiclone (7.5 mg) signiicantly impaired nextmorning driving after MOTN administration. Impairment with these drugs was worse than seen with a blood alcohol concentration (BAC) of 0.05%, i.e. the legal limit for driving in many countries. In contrast, buffered sublingual zolpidem tartate (3.5 mg) and zaleplon (10 mg and 20 mg) did not signiicantly affect driving 4 hours after MOTN administration. Except for sublingual zolpidem, all of the other medications are off label use for MOTN insomnia. Conclusion: Driving was not affected 4 hours after MOTN administration of sublingual zolpidem tartate (3.5 mg) or zaleplon (10 mg and 20 mg). Signiicant driving impairment was found after MOTN administration of zolpidem (10 and 20 mg), gaboxadol (15 mg), and zopiclone (7.5 mg).