对 Z 类药物滥用和依赖的洞察：对向欧洲药品管理局疑似药物不良反应数据库报告的审查。
An Insight into Z-Drug Abuse and Dependence: An Examination of Reports to the European Medicines Agency Database of Suspected Adverse Drug Reactions.
机构信息
Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom.
出版信息
Int J Neuropsychopharmacol. 2019 Apr 1;22(4):270-277. doi: 10.1093/ijnp/pyz007.
BACKGROUND
Although originally marketed as safe alternatives to the habit-forming benzodiazepines, growing numbers of zaleplon, zolpidem, and zopiclone ("Z-drugs") clinical concerns relating to their potential of abuse, dependence, and withdrawal have been reported over time. We aimed here at assessing these issues analyzing datasets of adverse drug reactions provided by the European Medicines Agency through the EudraVigilance system.
METHODS
Analyzing the adverse drug reactions databases of each Z-drug, descriptive analyses have been performed on cases and proportional reporting ratios (PRRs) computed.
RESULTS
An overall number of 33 240 (e.g., 23 420 zolpidem; 9283 zopiclone; and 537 zaleplon) misuse-, abuse-, dependence-, and withdrawal-related adverse drug reactions, corresponding to some 6246 unique patients given Z-drugs, were here identified. Cases were studied and described, including demographic characteristics and clinical data such as concomitant drugs, doses, routes of administration, and outcomes of the reactions (being fatalities recorded). Considering PRR values and in comparison with zopiclone, zolpidem was more frequently involved in both misuse/abuse and withdrawal issues. Zolpidem and zopiclone presented with the same dependence risk, but zopiclone was most involved in overdose adverse drug reactions. Compared with zaleplon, zopiclone presented higher dependence and overdose-related issues but slightly lower misuse/abuse and withdrawal PRR values.
CONCLUSION
Current data may only represent a gross underestimate of the real prevalence of Z-drug misuse. Caution should be exercised when prescribing those molecules, especially for patients with psychiatric illnesses and/or history of drug abuse. We recommend the need to invest in proactive pharmacovigilance activities to better and promptly detect, understand, and prevent any possible misuse potential of prescribed medications.
背景
尽管佐匹克隆、扎来普隆和唑吡坦最初被宣传为苯二氮䓬类药物的安全替代品，但随着时间的推移，越来越多的临床医生报告了与这些药物滥用、依赖和戒断相关的问题。我们旨在通过欧洲药品管理局（EMA）通过 EudraVigilance 系统提供的不良药物反应数据评估这些问题。
方法
对每种 Z 药物的不良药物反应数据库进行分析，对病例进行描述性分析，并计算比例报告比（PRR）。
结果
共发现 33240 例（例如 23420 例佐匹克隆；9283 例唑吡坦；537 例扎来普隆）与误用、滥用、依赖和戒断相关的不良药物反应，涉及约 6246 名接受 Z 药物治疗的独特患者。对这些病例进行了研究和描述，包括人口统计学特征和临床数据，如伴随用药、剂量、给药途径以及反应的结果（记录了死亡事件）。考虑到 PRR 值，与佐匹克隆相比，扎来普隆更频繁地涉及误用/滥用和戒断问题。唑吡坦和佐匹克隆具有相同的依赖风险，但佐匹克隆更易发生过量用药不良药物反应。与扎来普隆相比，佐匹克隆呈现出更高的依赖和过量相关问题，但误用/滥用和戒断 PRR 值略低。
结论
目前的数据可能仅代表 Z 药物滥用的真实流行率的粗略低估。在开处方时应谨慎使用这些药物，尤其是对有精神疾病和/或药物滥用史的患者。我们建议有必要投资于积极的药物警戒活动，以更好、更及时地发现、理解和预防处方药物的任何潜在滥用风险。
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