Influence of Zolpidem and Sleep Inertia on Balance and Cognition During Nighttime Awakening: A Randomized Placebo-Controlled Trial

Sleep and Chronobiology Laboratory, Department of Integrative Physiology, Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Journal of the American Geriatrics Society (Impact Factor: 4.57). 01/2011; 59(1):73-81. DOI: 10.1111/j.1532-5415.2010.03229.x
Source: PubMed

ABSTRACT To determine whether sleep inertia (grogginess upon awakening from sleep) with or without zolpidem impairs walking stability and cognition during awakenings from sleep.
Three within-subject conditions hypnotic medication (zolpidem), placebo (sleep inertia), and wakefulness control randomized using balanced Latin square design.
Sleep laboratory.
Twelve older and 13 younger healthy adults.
Five milligrams of zolpidem or placebo 10 minutes before scheduled sleep (double-blind: zolpidem or sleep inertia); placebo before sitting in bed awake for 2 hours after their habitual bedtime (single-blind: wakefulness control).
Tandem walk on a beam and cognition, measured using computerized performance tasks, approximately 120 minutes after treatment.
No participants stepped off the beam on 10 practice trials. Seven of 12 older adults stepped off the beam after taking zolpidem, compared with none after sleep inertia and three after wakefulness control. Fewer young adults stepped off the beam: three after taking zolpidem, one after sleep inertia, and none after wakefulness control. Number needed to harm analyses showed one tandem walk failure for every 1.7 (95% confidence interval (CI)=1.4-2.0) older and 5.5 (95% CI=5.2-5.8) younger adults treated with zolpidem. Cognition was significantly more impaired after zolpidem exposure than with wakefulness control in older and younger participants (working memory: older, -4.3 calculations, 95% CI=-7.0 to -1.7; younger, -12.4 calculations, 95% CI=-18.2 to -6.7; Stroop: older, 76-ms increase (95% CI=13.5-138.4 ms); younger, 126-ms increase, 95% CI=34.7-217.5 ms), whereas sleep inertia significantly impaired cognition in younger but not older participants.
Zolpidem produced clinically significant balance and cognitive impairments upon awakening from sleep. Because impaired tandem walk predicts falls and hip fractures and because impaired cognition has important safety implications, use of nonbenzodiazepine hypnotic medications may have greater consequences for health and safety than previously recognized.

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    • "Benzodiazepines have been associated with increased risk of hip fracture, but estimates diverge [6–10]. Z-hypnotics have previously been considered less harmful [11], but growing evidence suggests that they are not safer than benzodiazepines regarding either falls [12] or hip fractures [13, 14]. "
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    ABSTRACT: Purpose Anxiolytics and hypnotics are widely used and may cause injurious falls. We aimed to examine associations between exposure to anxiolytics and hypnotics and the risk of hip fracture among all older people in Norway. Further, we wanted to examine associations between exposure to hypnotics and time of fracture. Methods A nationwide prospective cohort study of people in Norway born before 1945 (n = 906,422) was conducted. We obtained information on all prescriptions of anxiolytics and hypnotics dispensed in 2004–2010 (the Norwegian Prescription Database) and all primary hip fractures in 2005–2010 (the Norwegian Hip Fracture Registry). We compared the incidence rates of hip fracture during drug exposure and non-exposure by calculating the standardized incidence ratio (SIR). Results Altogether, 39,938 people (4.4 %) experienced a primary hip fracture. The risk of hip fracture was increased for people exposed to anxiolytics (SIR 1.4, 95 % confidence interval (CI) 1.4–1.5) and hypnotics (SIR 1.2, 95 % CI 1.1–1.2); the excess risk was highest regarding short-acting benzodiazepine anxiolytics (SIR 1.5, 95 % CI 1.4–1.6). Benzodiazepine-like hypnotics (z-hypnotics) were associated with higher excess risk of hip fracture at night (SIR 1.3, 95 % CI 1.2–1.4) than during the day (SIR 1.1, 95 % CI 1.1–1.2). Conclusions Older people had an increased risk of hip fracture during anxiolytic or hypnotic drug use, including short-acting benzodiazepine anxiolytics and z-hypnotics that were previously considered less harmful; cautious prescribing is therefore needed. People using z-hypnotics were at greatest excess risk at night; this association deserves further investigation.
    European Journal of Clinical Pharmacology 07/2014; 70(7). DOI:10.1007/s00228-014-1684-z · 2.97 Impact Factor
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    ABSTRACT: To determine whether zolpidem is a safer alternative to benzodiazepines. Retrospective cohort study. Community based. Health maintenance organization members with an initial prescription for zolpidem (n = 43,343), alprazolam (n = 103,790), lorazepam (n = 150,858), or diazepam (n = 93,618). Zolpidem and benzodiazepine prescriptions were identified from pharmacy databases. Rates of nonvertebral fractures and hip fractures requiring hospitalization were compared before and after an initial prescription for each treatment, adjusting for confounders using doubly robust estimation. In patients aged 65 and older, the rates of nonvertebral fractures and dislocations were similar in the pre- treatment intervals. The rate ratios (RRs) for the 90-day posttreatment interval relative to the pretreatment interval were 2.55 (95% confidence interval (CI) = 1.78-3.65; P < .001) for zolpidem, 1.14 (95% CI = 0.80-1.64; P = .42) for alprazolam, 1.53 (95% CI = 1.23-1.91; P < .001) for lorazepam, and 1.97 (95% CI = 1.22-3.18; P = .01) for diazepam. The ratio of RRs (RRR)-the RR in the posttreatment period adjusted for the corresponding RR in the pretreatment period-were 2.23 (95% CI = 1.36-3.66; P = .006) for zolpidem relative to alprazolam, 1.68 (95% CI = 1.12-2.53; P = .02) for zolpidem relative to lorazepam, and 1.29 (95% CI = 0.72-2.30; P = .32) for zolpidem relative to diazepam. The RRs decreased with time from the initial prescription (trend P < .001), as would be expected if the association is causal. In older adults, the risk of injury with zolpidem exceeded that with alprazolam and lorazepam and was similar to that with diazepam. If the associations are causal, then the high incidence of these fractures implies that these treatment induce a substantial number of fractures and consequential costs. Further study of the association is imperative.
    Journal of the American Geriatrics Society 10/2011; 59(10):1883-90. DOI:10.1111/j.1532-5415.2011.03591.x · 4.57 Impact Factor
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    ABSTRACT: Impaired driving associated with sedative/hypnotic use is often called sleep driving. Sleep driving is most often described as a variant of sleepwalking. A recent case provides the first complete clinical history and description of a sleep-driving case associated with sleepwalking from beginning to end. Sleepwalking-related behavior accounted for the onset and beginning of the episode. However, residual drug effects were also required to account for the driver's behavior at the end of the episode. Sleepwalking and residual drug effects after an awakening may overlap and be required to account for the impaired driver's behavior.
    Sleep Medicine Clinics 12/2011; 6(4):441-445. DOI:10.1016/j.jsmc.2011.08.003
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