Middle-of-the-Night Administration of Sleep Medication: A Critical Review of the Effects on Next Morning Driving Ability
Joris C. Verster, Aurora J.A.E. van de Loo, Margaret L. Moline and Thomas Roth
Affiliation: Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacology, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Study Objectives: Sleep maintenance problems are common, hence treatments enabling patients to fall asleep
more rapidly after middle-of-the-night (MOTN) awakenings, without impairing next morning alertness, are needed. This
literature review compares the effects of MOTN administration of various hypnotics on morning driving ability, a
potentially dangerous daily activity under conditions of impairment.
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
traffic, subjects were instructed to drive with a steady lateral position and constant speed of 95 km/h. The primary
outcome measure of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), i.e. weaving of the car.
Results: Four driving studies were identified. Driving performance after MOTN administration of traditional
benzodiazepine hypnotics was not examined. Zolpidem (10 mg and 20 mg, oral immediate release tablets) significantly
impaired driving in a dose-dependent manner, when tested 4 hours after MOTN administration. Also, gaboxadol (15 mg)
and zopiclone (7.5 mg) significantly impaired next-morning driving after MOTN administration. In contrast, sublingual
zolpidem (3.5 mg) and zaleplon (10 mg and 20 mg) did not significantly affect driving 4 hours after MOTN
Conclusion: Driving was not affected 4 hours after MOTN administration of sublingual zolpidem (3.5 mg) or zaleplon (10
mg and 20 mg). Significant driving impairment was found after MOTN administration of zolpidem (10 and 20 mg),
gaboxadol (15 mg), and zopiclone (7.5 mg).
Keywords: Benzodiazepines, driving, hypnotic drugs, middle-of-the-night, sleep medication, zolpidem.
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