Dolder Christian R, Nelson Michael H
Wingate University School of Pharmacy, Wingate, North Carolina 28174, USA.
CNS Drugs. 2008;22(12):1021-36. doi: 10.2165/0023210-200822120-00005.
A number of news items and case reports describing complex behaviours (e.g. sleep driving, sleep cooking, sleep eating, sleep conversations, sleep sex) associated with the use of hypnosedative medications have recently received considerable attention. Regulatory agencies examining these reports have subsequently issued warnings regarding the potential of hypnosedative agents to produce complex behaviours. Despite these warnings, little is known about the likelihood, presentation, treatment or prevention of hypnosedative-induced complex behaviours. The purpose of this review is to evaluate the published evidence regarding the clinical presentation, incidence, mechanism and management of sleep-related behaviours induced by nonbenzodiazepine receptor agonists (NBRAs).Review of the literature identified ten published case reports of NBRA-induced complex behaviours involving 17 unique patients. Fifteen of the 17 patients described in the case reports had taken zolpidem, one had taken zaleplon and one had taken zopiclone. The complex behaviours most commonly reported were sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping. Elevated serum concentrations resulting from increased medication dose or drug-drug interactions appeared to play a role in some but not all cases. Sex, age, previous medication exposure and concomitant disease states were not consistently found to be related to the risk of experiencing a medication-induced complex behaviour.From a pharmacological standpoint, enhancement of GABA activity at GABAA receptors (particularly alpha1-GABAA receptors) is a possible mechanism for hypnosedative complex behaviours and amnesia. Evidence suggests that complex behaviour risk may increase with both dose and binding affinity at alpha1-GABAA receptors. The amnesia that accompanies complex behaviours is possibly due to inhibition of consolidation of short- to long-term memory, suggesting that the risk may extend to non-GABAergic hypnosedatives. While amnesia and GABA-related receptor actions are the most frequently discussed mechanisms for complex behaviours in the literature, they do not fully explain such behaviours, suggesting that other mechanisms and factors probably play a role.A number of potential strategies are available to manage or prevent hypnosedative-induced complex behaviours. These include lowering the dose of, or stopping, the offending hypnosedative, switching to a different hypnosedative, treating patients with other classes of medications, using nonpharmacological treatment strategies for patients with sleep disorders, examining drug regimens for potential drug interactions that may predispose patients to experiencing complex behaviours, administering hypnosedative medications appropriately and selecting patients more carefully for treatment in terms of their likelihood of experiencing medication adverse effects.
最近，一些新闻报道和病例报告描述了与使用催眠镇静药物相关的复杂行为（如睡眠驾驶、睡眠烹饪、睡眠进食、睡眠交谈、睡眠性行为），这些报道受到了广泛关注。审查这些报告的监管机构随后发布了关于催眠镇静药物产生复杂行为可能性的警告。尽管有这些警告，但对于催眠镇静药物引起的复杂行为的可能性、表现、治疗或预防知之甚少。本综述的目的是评估已发表的关于非苯二氮䓬受体激动剂（NBRAs）引起的与睡眠相关行为的临床表现、发生率、机制和管理的证据。对文献的回顾确定了10篇已发表的关于NBRAs引起的复杂行为的病例报告，涉及17例独特的患者。病例报告中描述的17例患者中有15例服用了唑吡坦，1例服用了扎来普隆，1例服用了佐匹克隆。最常报告的复杂行为是睡眠进食、伴有物体操纵的梦游、睡眠交谈、睡眠驾驶、睡眠性行为和睡眠购物。在一些但并非所有病例中，药物剂量增加或药物相互作用导致的血清浓度升高似乎起到了一定作用。性别、年龄、既往用药史和伴随疾病状态并未始终被发现与发生药物引起的复杂行为的风险相关。从药理学角度来看，增强GABAA受体（特别是α1-GABAA受体）处的GABA活性是催眠镇静药物引起复杂行为和失忆的一种可能机制。有证据表明，复杂行为风险可能随着剂量和在α1-GABAA受体处的结合亲和力而增加。伴随复杂行为出现的失忆可能是由于短期到长期记忆巩固的抑制，这表明风险可能扩展到非GABA能催眠镇静药物。虽然失忆和与GABA相关的受体作用是文献中最常讨论的复杂行为机制，但它们并不能完全解释这些行为，这表明其他机制和因素可能也起到了作用。有多种潜在策略可用于管理或预防催眠镇静药物引起的复杂行为。这些策略包括降低或停用引起问题的催眠镇静药物、换用其他催眠镇静药物、用其他类别的药物治疗患者、对睡眠障碍患者使用非药物治疗策略、检查药物治疗方案中可能使患者易发生复杂行为的潜在药物相互作用、适当使用催眠镇静药物以及根据患者发生药物不良反应的可能性更谨慎地选择治疗患者。
