In the Zzz Zone: The Effects of Z-Drugs on Human Performance and Driving

Abstract

Despite their improved pharmacokinetic profile, the Z-drugs, zolpidem, zopiclone, and zaleplon, have a spectrum of adverse effects comparable to benzodiazepines. This review focuses on the impairment from Z-drugs on cognition, behavior, psychomotor performance, and driving ability. Z-drugs are short-acting GABA agonists that reduce sleep latency without disturbing sleep architecture. Bizarre behavioral effects have prompted warnings on the prescription, dispensation, and use of Z-drugs. Psychomotor impairment, falls, and hip fractures are more likely to occur with Z-drugs that have longer half-lives, that are taken at higher-than-recommended doses and when mixed with other psychoactive substances including alcohol. Zopiclone and higher doses of zolpidem are more likely to cause anterograde amnesia than zaleplon. Z-drugs, especially zolpidem, are associated with complex behaviors such as sleepwalking, sleep-driving, and hallucinations. Patients taking zopiclone and zolpidem have an increased risk of motor vehicle collisions, over double that of unexposed drivers. Driving impairment occurs with zopiclone and higher doses of zolpidem but is unlikely to occur after 4 h post-zaleplon administration. The residual effect of Z-drugs on next-day cognitive and psychomotor performance has significant impact on lifestyle, safety, and occupational considerations, including motor vehicle and machine operation. The risk-benefit analysis of Z-drugs in the treatment of insomnia, particularly in the elderly, may not favor treatment due to the increased risks of falls and motor vehicle collisions. Prescribers should warn patients taking Z-drugs of minimum time thresholds before they operate machinery or drive motor vehicles.

A Randomized, Double-Blind, Single-Dose, Placebo-Controlled, Multicenter, Polysomnographic Study of Gabapentin in Transient Insomnia Induced by Sleep Phase Advance

“…These are important observations and distinguish gabapentin from various other hypnotic agents, both prescription and OTC, which have been reported to be associated with next-day residual effects. 34,[39][40][41] Overall, there were no clinically meaningful differences in AE frequency or vital sign changes among the three treatment groups. No new safety concerns were identified during the trial.…”

The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation of Wake-Promoting Systems

“…ZOL and similar drugs like eszopiclone are widely prescribed and generally considered effective at inducing sleep (Greenblatt and Roth, 2012), but their use is associated with a high incidence of adverse effects such as driving impairment (Gunja, 2013;Verster et al, 2006), memory impairment (Balkin et al, 1992;Mintzer and Griffiths, 1999;Wesensten et al, 1995Wesensten et al, , 1996, complex sleep behaviors (Chen et al, 2014;Dolder and Nelson, 2008), and psychomotor deficits (Storm et al, 2007;Wesensten et al, 2005), highlighting the need for hypnotics that induce lessfunctional impairment. ALM and other HcrtR antagonists effectively induce sleep (Brisbare-Roch et al, 2007;Cox et al, 2010) but cause less impairment in memory tasks (Dietrich and Jenck, 2010;Morairty et al, 2014) or motor function in rodents (Ramirez et al, 2013;Steiner et al, 2011), dogs (Tannenbaum et al, 2014), and non-human primates (Uslaner et al, 2013) than do traditional hypnotics.…”

Use of benzodiazepines and related drugs in Manitoba: a population-based study

“…Although it has been suggested that Z-drugs have a lower potential for abuse and dependence, 9 their use can also be problematic because of their effects on human performance and driving. 10,11 Because of these potential adverse effects, clinical practice guidelines have advised against the use of benzodiazepines and Z-drugs for longer than 4 weeks, and health agencies worldwide have undertaken anti-benzodiazepine and anti-Z-drug campaigns, not without controversy. [12][13][14][15][16][17][18] However, the dearth of published research studies on this subject suggests that such recommendations have not had a significant impact on the use of benzodiazepines and Z-drugs in various countries.…”