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: 2.95). 06/2009; 18(4):387-96. DOI: 10.1111/j.1365-2869.2009.00746.x
Source: PubMed

ABSTRACT 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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Available from: Tim Leufkens, Aug 10, 2015
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    • "Trazodone's preferential prescription may be related to its perception as a safer substitute for other hypnotics. Standard hypnotics have been implicated in increased risk of motor vehicle accidents and memory problems (Leufkens et al., 2009). In contrast, trazodone's adverse behavioral effects have rarely been studied. "
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    ABSTRACT: Trazodone is prescribed widely as a sleep aid, although it is indicated for depression, not insomnia. Its daytime cognitive and psychomotor effects have not been investigated systematically in insomniacs. The primary goal of this study was to quantify, in primary insomniacs, the hypnotic efficacy of trazodone and subsequent daytime impairments. Sixteen primary insomniacs (mean age 44 years) participated, with insomnia confirmed by overnight polysomnography (sleep efficiency ≤ 85%). Trazodone 50 mg was administered to participants 30 min before bedtime for 7 days in a 3-week, within-subjects, randomized, double-blind, placebo-controlled design. Subjective effects, equilibrium (anterior/posterior body sway), short-term memory, verbal learning, simulated driving and muscle endurance were assessed the morning after days 1 and 7 of drug administration. Sleep was evaluated with overnight polysomnography and modified Multiple Sleep Latency Tests (MSLT) on days 1 and 7. Trazodone produced small but significant impairments of short-term memory, verbal learning, equilibrium and arm muscle endurance across time-points. Relative to placebo across test days, trazodone was associated with fewer night-time awakenings, minutes of Stage 1 sleep and self-reports of difficulty sleeping. On day 7 only, slow wave sleep was greater and objective measures of daytime sleepiness lower with trazodone than with placebo. Although trazodone is efficacious for sleep maintenance difficulties, its associated cognitive and motor impairments may provide a modest caveat to health-care providers.
    Journal of Sleep Research 05/2011; 20(4):552-8. DOI:10.1111/j.1365-2869.2011.00928.x · 2.95 Impact Factor
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    • "The results obtained with Zc confirmed those found in previous studies showing that this drug had residual effects the next morning in healthy subjects, young ( (Bocca et al. 1999; Leufkens et al. 2009; Vermeeren et al. 1998; Vermeeren et al. 2002) or old (Leufkens and Vermeeren 2009) as well as in middle-aged patients with insomnia (Staner et al. 2005). Comparisons of monotonous driving performance with different alcohol concentrations have revealed that in both young and aged subjects, the residual effects of Zc can be compared to a blood alcohol concentration (BAC) of about 0.5 g/L (Vermeeren 2004). "
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    ABSTRACT: Although hypnotics are primarily used by older people, the residual effects the morning after a single nighttime intake of the two most commonly prescribed hypnotics, zolpidem (Zp) and zopiclone (Zc), on older middle-aged drivers have not been evaluated and compared. Sixteen healthy subjects, 55 to 65 years of age, participated in this double-blind, balanced, cross-over study. Zc (7.5 mg), Zp (10 mg) and flunitrazepam (Fln) (1 mg) or a placebo was administered at each subject's home at 11.00 pm. The next morning, at 9.00 am, the subjects had to drive in a simulated monotonous driving environment for 1 h. During each morning session, two blood samples were collected, and subjective feelings of alertness were completed three times. In comparison to placebo, Zp and Zc equivalently and significantly impaired the standard deviation of lateral position, the standard deviation of speed and the number of road exits. Detectable blood concentrations were found with Zp in 11 subjects at 8.30 am and at 1.30 pm. The subjective alertness factor was significantly impaired with Zp. This is the first study revealing residual effects of Zp on driving performance in ageing drivers which are similar to that of Zc. Studying the effects of medication in different age ranges appears useful to complete the studies on behavioural-pharmacological effects of medication. To reduce the incidence of driving accidents due to prescription drugs, patients should be warned at the time of treatment initiation that they should avoid driving.
    Psychopharmacology 11/2010; 214(3):699-706. DOI:10.1007/s00213-010-2075-5 · 3.99 Impact Factor
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