Designer benzodiazepines: a report of exposures recorded in the National Poison Data System, 2014–2017

<b>Importance:</b> Exposures to novel psychoactive substances are reported with increasing frequency in both the medical literature and the lay press. While the majority of reports describe synthetic cannabinoids and cathinones, a lesser understood family is the “designer benzodiazepines”. The current literature describing human exposures to these compounds is comprised of case reports and small case series. <b>Objective:</b> The primary objectives of this study are to describe epidemiologic trends and clinical effects of designer benzodiazepine use. <b>Methods:</b> Data regarding single agent exposures to designer benzodiazepines between 1 January 2014 and 31 December 2017 was obtained from the National Poison Data System. Substances queried include: adinazolam, clonazolam, cloniprazepam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, nifoxipam, norflurazepam, and pyrazolam. Data was summarized descriptively. <b>Results:</b> 234 single agent exposures in 40 states were reported during the study period. The annual number of exposures increased each year, from 26 in 2014 to 112 in 2017, amounting to a 330% increase. The most common exposures were etizolam (<i>n</i> = 162) and clonazolam (<i>n</i> = 50). The most common clinical effects were drowsiness/lethargy (65%), and slurred speech (17%). 3% required intubation, 36% of cases required hospital admission, 22% to the intensive care unit. There was 1 death in the study population. <b>Conclusions:</b> The incidence of exposures to designer benzodiazepines is rising. Clinical effects are generally consistent with a sedative-hypnotic toxidrome. Severe effects, including death, seemed relatively uncommon in the study population.

**研究背景与意义**：新型精神活性物质暴露的相关报道在医学文献与大众媒体中愈发频繁。现有报道多聚焦于合成大麻素与卡西酮类物质，而“设计类苯二氮䓬类（designer benzodiazepines）”则是一类认知程度较低的化合物家族。目前针对此类化合物人体暴露的相关文献，仅由个案报告与小型病例系列研究构成。
**研究目的**：本研究的核心目标为阐明设计类苯二氮䓬类药物使用的流行病学趋势与临床效应。
**研究方法**：本研究从美国国家毒物数据系统（National Poison Data System）提取2014年1月1日至2017年12月31日期间，单一药物暴露于设计类苯二氮䓬类的相关数据。所纳入查询的物质包括：阿地唑仑（adinazolam）、氯唑仑（clonazolam）、氯尼西泮（cloniprazepam）、二氯西泮（diclazepam）、依替唑仑（etizolam）、氟溴西泮（flubromazepam）、氟溴唑仑（flubromazolam）、甲氯西泮（meclonazepam）、尼福西泮（nifoxipam）、去甲氟西泮（norflurazepam）以及吡唑仑（pyrazolam）。研究数据采用描述性汇总分析方法进行整理。
**研究结果**：本研究周期内，全美40个州共报告234例单一药物暴露事件。年度暴露例数逐年递增，从2014年的26例升至2017年的112例，增幅达330%。最常见的暴露物质为依替唑仑（*n*=162）与氯唑仑（*n*=50）。最频发的临床效应为嗜睡/昏睡（占比65%）以及言语含糊（占比17%）。3%的病例需实施气管插管，36%的病例需住院治疗，其中22%收入重症监护病房。研究队列中仅出现1例死亡病例。
**研究结论**：设计类苯二氮䓬类药物暴露的发生率呈上升趋势。其临床效应总体符合镇静催眠类药物中毒综合征。本研究队列中，包括死亡在内的严重效应相对罕见。