Highway driving performance and cognitive functioning the morning after bedtime and middle-of-the-night use of gaboxadol, zopiclone and zolpidem

Experimental Psychopharmacology Unit, Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Journal of Sleep Research (Impact Factor: 3.35). 06/2009; 18(4):387-96. DOI: 10.1111/j.1365-2869.2009.00746.x
Source: PubMed


Gaboxadol is a selective extrasynaptic GABA(A) receptor agonist previously in development for the treatment of insomnia. Due to its short half-life (1.5-2 h) it is expected to be free from residual effects the next morning. The present study assessed the residual effects of evening and middle-of-the-night administration of 15 mg of gaboxadol on cognitive, psychomotor and driving performance. Twenty-eight healthy volunteers entered the study with 25 (12 women; mean age 31.4 years) completing a double-blind, placebo-controlled, active-referenced five-way cross-over study. Each treatment night subjects ingested one capsule at 23:00 hours and one at 04:00 hours. Treatments were placebo at both times, 15 mg gaboxadol or 7.5 mg zopiclone followed by placebo, and placebo followed by 15 mg gaboxadol or 10 mg zolpidem. Effects on cognition and psychomotor performance were assessed between 07:30 and 08:30 hours and on driving between 09:00 and 10:00 hours. Driving, as measured by standard deviation of lateral position in an on-the-road driving test, was almost significantly (P < 0.07) impaired after evening administration of gaboxadol for the all-subjects-completed set (n = 25) but significantly (P < 0.05) in the full analysis set (n = 28). Effects of all other active treatments on driving were significant. Evening administration of gaboxadol had minor effects on divided attention only, whereas middle-of-the-night administration impaired performance significantly in all tests except memory. Zolpidem and zopiclone impaired performance significantly in every test except tracking after zopiclone; 15 mg of gaboxadol can produce minor residual effects on driving after evening administration. Administration later at night is associated with moderately impairing residual effects on driving and psychomotor performance but not on memory.

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    • "fkens et al. 2009b). A similar finding was demonstrated for gaboxadol, a GABA-a receptor agonist. Driving performance was unimpaired after an of the studies testing hypnotics in the on-the-road driving test. The acute and subchronic effects are indicated in terms of blood alcohol concentration (BAC) required to achieve the same level of impairment. et al. Leufkens et al. 2009b A, afternoon; BAC, blood alcohol concentration; M, morning; MOTN, middle-of-the-night administration. a Levels of 0.5 g/L or greater are given in bold. 1986; Leufkens et al. 2009a)), while triazolam increased SDLP both on day 1 and day 5 (equivalent to BACs of >0.8 and 1.0 g/L respectively) and midazolam increased SDLP only on day 5 (eq"
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    ABSTRACT: This chapter concentrates on the effect of psychoactive prescription drugs on driving performance using the on-the-road driving test. It provides an overview of medicinal drugs that could impair driving performance as tested with the on-the-road driving test. Hypnotics are meant to induce sleep in patients who suffer from insomnia. However, hypnotic drugs often cause residual sedation the morning after evening- or middle-of-the-night (MOTN) administration which may lead to impaired driving performance. Anxiolytic drugs are used for treatment of anxiety. The chapter provides an overview of the results of antidepressants on the on-the-road driving test. It talks about other drugs like antiepileptic drugs and methylphenidate. It is essential that drugs are screened thoroughly on their potential to affect patients' driving performance and that patients receive the most up-to-date information about the impairing potential of the drugs they are using.
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    • "In epidemiological studies, for example, it has been shown that use of hypnotics is related to an increased risk of becoming involved in traffic and occupational accidents (Ray et al. 1992; Hemmelgarn et al. 1997; Barbone et al. 1998; Neutel 1998; Dubois et al. 2008; Dassanayake et al. 2011). Experimental studies assessing actual driving performance after administration of hypnotics confirm these data by showing residual driving impairment in the morning after dosing (Volkerts and O’Hanlon 1988; Vermeeren 1995; Vermeeren et al. 1998, 2002; Verster et al. 2002; Leufkens et al. 2009). "
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    • "The results of this study help further research to quantify drug effects. For example, the hypnotics gaboxadol (15 mg) and zolpidem (10 mg) taken in the middle of the night were found to increase reaction time in the DAT the next morning on average by 184 ms (Leufkens et al. 2009). These effects are comparable to the effects of a BAC of 0.8 g/L on the same test in the present study. "
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