Association of eszopiclone, zaleplon, or zolpidem with complex sleep behaviors resulting in serious injuries, including death

Harbourt, Kelly; Nevo, Ofir Noah; Zhang, Rongmei; Chan, Vicky; Croteau, David

doi:10.1002/pds.5004

Cited by 26 publications

(13 citation statements)

References 14 publications

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“…Withdrawal from short-acting hypnotics, such as triazolam, can be followed by automatisms at night, with amnesia the next day for the behavior. Withdrawal from bedtime doses of zolpidem, zaleplon, zopiclone, and eszopiclone has been associated in a few reported cases with complex sleep behaviors, including sleep driving [192], resulting in injury or, in a small number of individuals, death from automobile crashes, hypothermia, overdoses, falls, and gunshot wounds [193]. Rebound insomnia is more common than other discontinuation syndromes with eszopiclone.…”

Section: Issues Complicating Benzodiazepine Usementioning

confidence: 99%

Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice

Dubovsky

Marshall

2022

Psychother Psychosom

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Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.

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Section: Issues Complicating Benzodiazepine Usementioning

confidence: 99%

Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice

Dubovsky

Marshall

2022

Psychother Psychosom

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“…Z-drugs, and zolpidem in particular, are more often associated with complex sleep behaviours (e.g., parasomnias) then benzodiazepines ( Harbourt et al, 2020 ). This may be explained by the maintenance of slow-wave sleep combined with the decreased muscle-relaxing effect of Z-drugs compared to benzodiazepines ( Chopra et al, 2013 ).…”

Section: Preventive Strategiesmentioning

confidence: 99%

Fatigue in Aviation: Safety Risks, Preventive Strategies and Pharmacological Interventions

Wingelaar-Jagt

Wingelaar²,

Riedel

et al. 2021

Front. Physiol.

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Fatigue poses an important safety risk to civil and military aviation. In addition to decreasing performance in-flight (chronic) fatigue has negative long-term health effects. Possible causes of fatigue include sleep loss, extended time awake, circadian phase irregularities and work load. Despite regulations limiting flight time and enabling optimal rostering, fatigue cannot be prevented completely. Especially in military operations, where limits may be extended due to operational necessities, it is impossible to rely solely on regulations to prevent fatigue. Fatigue management, consisting of preventive strategies and operational countermeasures, such as pre-flight naps and pharmaceuticals that either promote adequate sleep (hypnotics or chronobiotics) or enhance performance (stimulants), may be required to mitigate fatigue in challenging (military) aviation operations. This review describes the pathophysiology, epidemiology and effects of fatigue and its impact on aviation, as well as several aspects of fatigue management and recommendations for future research in this field.

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“…In April 2019, the FDA added a Boxed Warning to the prescribing information for zolpidem highlighting the risk of rare, albeit serious, injuries (including deaths) due to adverse sleep behaviors, including sleepwalking, sleep driving, and other activities while not fully awake. Common zolpideminduced delirium and sleep-related complex behavior include accidents, falls, overdoses as well as risks to others included assaults, vehicular accidents, various crimes, and civil actions that occurred during zolpidem-induced delirium and sleep related complex behaviors (Greenblatt and Zammit, 2012;Park et al, 2016;FDA, 2019a;Harbourt et al, 2020;Westermeyer and Carr, 2020). Recently and increased concern has been developed regarding its misuse and risk of abuse (Schifano et al, 2019).…”

Section: Zolpidemmentioning

confidence: 99%

“…Zaleplon 10 mg has also been shown to be free of residual hypnotic or sedative effects despite nocturnal administration as little as 2 h before waking in normal subjects compared with zolpidem (Danjou et al, 1999). In April 2019, the FDA added a Boxed Warning for Z-drugs, including zaleplon, advising that rare but serious injuries have happened because of sleep behaviors, including sleepwalking, sleep driving, and engaging in other activities while not fully awake (Greenblatt and Zammit, 2012;Park et al, 2016;FDA, 2019a;Harbourt et al, 2020;Westermeyer and Carr, 2020).…”

Section: Zaleplonmentioning

confidence: 99%

Pharmacotherapeutic management of insomnia and effects on sleep processes, neural plasticity, and brain systems modulating stress: A narrative review

Palagini

Bianchini

2022

Front. Neurosci.

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IntroductionInsomnia is a stress-related sleep disorder, may favor a state of allostatic overload impairing brain neuroplasticity, stress immune and endocrine pathways, and may contribute to mental and physical disorders. In this framework, assessing and targeting insomnia is of importance.AimSince maladaptive neuroplasticity and allostatic overload are hypothesized to be related to GABAergic alterations, compounds targeting GABA may play a key role. Accordingly, the aim of this review was to discuss the effect of GABAA receptor agonists, short-medium acting hypnotic benzodiazepines and the so called Z-drugs, at a molecular level.MethodLiterature searches were done according to PRISMA guidelines. Several combinations of terms were used such as “hypnotic benzodiazepines” or “brotizolam,” or “lormetazepam” or “temazepam” or “triazolam” or “zolpidem” or “zopiclone” or “zaleplon” or “eszopiclone” and “insomnia” and “effects on sleep” and “effect on brain plasticity” and “effect on stress system”. Given the complexity and heterogeneity of existing literature, we ended up with a narrative review.ResultsAmong short-medium acting compounds, triazolam has been the most studied and may regulate the stress system at central and peripheral levels. Among Z-drugs eszopiclone may regulate the stress system. Some compounds may produce more “physiological” sleep such as brotizolam, triazolam, and eszopiclone and probably may not impair sleep processes and related neural plasticity. In particular, triazolam, eszopiclone, and zaleplon studied in vivo in animal models did not alter neuroplasticity.ConclusionCurrent models of insomnia may lead us to revise the way in which we use hypnotic compounds in clinical practice. Specifically, compounds should target sleep processes, the stress system, and sustain neural plasticity. In this framework, among the short/medium acting hypnotic benzodiazepines, triazolam has been the most studied compound while among the Z-drugs eszopiclone has demonstrated interesting effects. Both offer potential new insight for treating insomnia.

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Association of eszopiclone, zaleplon, or zolpidem with complex sleep behaviors resulting in serious injuries, including death

Cited by 26 publications

References 14 publications

Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice

Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice

Fatigue in Aviation: Safety Risks, Preventive Strategies and Pharmacological Interventions

Pharmacotherapeutic management of insomnia and effects on sleep processes, neural plasticity, and brain systems modulating stress: A narrative review

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