Exposure-Response Association Between Concurrent Opioid and Benzodiazepine Use and Risk of Opioid-Related Overdose in Medicare Part D Beneficiaries
Exposure-Response Association Between Concurrent Opioid and Benzodiazepine Use and Risk of Opioid-Related Overdose in Medicare Part D Beneficiaries
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DOI：
10.1001/jamanetworkopen.2018.0919
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发表时间：
2018-06-01
影响因子：
13.8
通讯作者：
Zhang, Yuting
中科院分区：
文献类型：
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作者：
Hernandez, Inmaculada;He, Meiqi;Zhang, Yuting
重要性同时使用苯二氮卓类药物与阿片类药物相关过量风险增加相关;然而，目前尚不清楚过量风险如何随着暴露于两种药物的天数而变化。目的评估同时使用处方阿片类药物和苯二氮卓类药物的天数与过量风险之间的因果关系。和参与者回顾性队列研究的医疗保险D部分索赔数据从2013年1月1日至2014年12月31日。分析于2017年秋季和2018年春季进行。参与者是医疗保险D部分受益人，他们在2014年至少开了1张阿片类药物处方。暴露患者根据服药过量或审查前一天是否有阿片类药物和苯二氮卓类药物供应被分为2组。第一组仅供应阿片类药物（n = 50 583），第二组供应阿片类药物和苯二氮卓类药物（n = 20 665）。根据阿片类药物和苯二氮卓类药物重叠供应的累积天数，将第二组进一步分为4个亚组：伊藤90天（n = 3603），91 - 180天（n = 2930），181 - 270天（n = 4082），271天或以上（n = 10 050）。主要结果和测量构建考克斯比例风险模型以比较阿片类药物相关过量（包括致命和非致命药物过量），控制人口统计学特征、保险因素、临床特征以及独特阿片类药物和苯二氮卓类药物处方者的数量。结果在总共71248名参与者中，男性25 600人（35.9%），白色59 532人（83.6%）。平均（SD）年龄为66.5（14.8）岁。在药物过量或删失事件前一天，71248例接受阿片类药物处方的患者中有20665例（29.0%）同时使用苯二氮卓类药物，20665例同时使用者中有14132例（68.4%）两种药物的重叠供应超过180天。在同时使用阿片类药物和苯二氮卓类药物的第一天，过量的风险最高，并随着时间的推移而降低;与单独使用阿片类药物相比，过量的风险比为5.05（95% CI，3.68-6.93）在同时使用阿片类药物和苯二氮卓类药物的前90天内，1.87（95%CI，1.25-2.80）在90天前没有发生事件的患者中，第91天至第180天。同时使用苯二氮卓类药物与阿片类药物相关过量风险增加5倍相关。有必要实施阻止类阿片和苯二氮卓类药物同时使用的政策。使用这两种药物的患者应密切监测，特别是在同时使用的第一天。
IMPORTANCE Concurrent benzodiazepine use is associated with an increased risk of opioid-related overdose; however, it remains unknown how the overdose risk varies with the days of exposure to both medications.OBJECTIVE To evaluate the exposure-response association between the days with concurrent prescription opioid and benzodiazepine use and the risk of overdose.DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of Medicare Part D claims data from January 1, 2013, to December 31, 2014. Analyses were conducted in fall 2017 and spring2018. Participants were Medicare Part D beneficiaries who filled at least 1 prescription for an opioid in 2014.EXPOSURES Patients were divided into 2 groups based on whether they had opioid and benzodiazepine supplies on the day before overdose or censoring. The first group only had a supply of opioids (n = 50 583) and the second group had supplies of opioids and benzodiazepines (n = 20 665). The second group was further categorized into 4 subgroups based on the cumulative number of days with overlapping supplies of opioids and benzodiazepines: Ito 90 days (n = 3603), 91 to 180 days (n = 2930), 181 to 270 days (n = 4082), and 271 days or more (n = 10 050).MAIN OUTCOMES AND MEASURES Cox proportional hazard models were constructed to compare opioid-related overdose (including fatal and nonfatal overdoses) across time-dependent treatment groups, controlling for demographic characteristics, insurance factors, clinical characteristics, and number of unique opioid and benzodiazepine prescribers.RESULTS Of 71 248 total participants, 25 600 (35.9%) were male and 59 532 (83.6%) were white. Mean (SD) age was 66.5 (14.8) years. On the day before overdose or censoring event, 20 665 of 71 248 patients with an opioid prescription (29.0%) were concurrently using benzodiazepines and 14 132 of 20 665 concurrent users (68.4%) had more than 180 days of overlapping supplies of both medications. The risk of overdose was highest on the first days of concurrent opioid and benzodiazepine use and decreased over time; compared with opioid use alone, the hazard ratio for overdose was 5.05 (95% CI, 3.68-6.93) during the first 90 days of concurrent opioid and benzodiazepine use and 1.87 (95% CI, 1.25-2.80) for days 91 to 180 among those who did not have an event before 90 days.CONCLUSIONS AND RELEVANCE During the first 90 days. concurrent benzodiazepine use is associated with a 5-fold increase in the risk of opioid-related overdose. The implementation of policies deterring concurrent opioid and benzodiazepine use is warranted. Patients using both medications should be closely monitored, particularly during the first days of concurrent use.