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

ArticleinJournal of the American Geriatrics Society 59(1):73-81 · January 2011with34 Reads
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.
    • "The first forced desynchrony assessed, in order: a 20-min visual vigilance task [Psychomotor Vigilance Task (PVT)], working memory/cognitive speed tasks [2-min mathematical addition test (ADD)] and a 1.5-min Digit Symbol Substitution Test (DSST) (). The second forced desynchrony assessed, in order: Karolinska Sleepiness Scale (KSS) and goaldirected behaviours and cognitive control on selective visual attention tasks [spatial-configuration visual search task (SPATIAL) and conjunction visual search task (CONJ)] () and cognitive speed and the inhibitory control component of executive function [Stroop Colour Word Task (STROOP)] (Frey et al., 2011 ) (descriptions of STROOP and visual search tasks in the Supporting information). "
    [Show abstract] [Hide abstract] ABSTRACT: Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. © 2015 European Sleep Research Society.
    Full-text · Article · Mar 2015
    • "Because these medications act via the benzodiazepine receptor- GABA complex, a similar side effect profile for non-benzodiazepine sedative-hypnotics and benzodiazepines is plausible. Indeed, clinical trials have reported comparable rates of CNS side effects, such as drowsiness, fatigue, impaired cognitive and motor function, postural sway, and ataxia67821222324. Due to its observational nature, our analysis has several limitations, most notably confounding by indication. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: To ascertain whether use of non-benzodiazepine sedative-hypnotics is associated with risk of falls and compare this to risk of falls associated with use of benzodiazepines. Methods: Among 4450 community-dwelling men, aged 71 years and older, enrolled in the population-based prospective cohort study, Osteoporotic Fractures in Men (MrOS), use of nonbenzodiazepine sedative-hypnotics and benzodiazepines was assessed by interview and verified from medication containers at the third annual visit of the MrOS study. Falls in the subsequent one-year period were ascertained by tri-annual questionnaires and a computerized dictionary used to categorize type of medication. Results: In age-adjusted models, non-benzodiazepine sedative hypnotic use was associated with an increased risk of any falls (one or more falls) (RR 1.44, 95% CI 1.15, 1.81) and recurrent falls (2 or more falls) (RR 1.51, 95% CI 1.07, 2.14). Use of benzodiazepines was associated with a similar increase in age-adjusted risk of falling. Depressive symptoms, inability to stand from a chair, and instrumental activities of daily living (IADL) impairment modestly attenuated these associations. The association between non-benzodiazepine sedative-hypnotic use and falls was most pronounced among men without a history of falls in the previous year: in a multivariable model controlling for multiple potential confounders, the RR of any falls was 1.74 (95% CI 1.13, 2.68) in this subgroup. Conclusions: Use of non-benzodiazepine sedative-hypnotics is associated with an increased risk of falls. Non-pharmacologic approaches to sleep disturbances may represent the safest approach to sleep difficulties in older adults.
    Article · Jul 2014
    • "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]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Jul 2014
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