BACKGROUND AND AIMS Benzodiazepines are commonly prescribed to patients with opioid use disorder receiving buprenorphine treatment, yet may increase overdose risk. However, prescribed benzodiazepines may improve retention in care by reducing buprenorphine discontinuation and thus may prevent relapse to illicit opioid use. We aimed to test the association between benzodiazepine prescription and fatal opioid overdose, non-fatal opioid overdose, all-cause mortality, and buprenorphine discontinuation. DESIGN AND SETTING This was a retrospective cohort study using 5 individually linked data sets from Massachusetts, USA government agencies. PARTICIPANTS We studied 63,389 Massachusetts residents aged 18 years or older who received buprenorphine treatment between January 2012 and December 2015. MEASUREMENTS Filled benzodiazepine prescription during buprenorphine treatment was the main independent variable. The primary outcome was time to fatal opioid overdose. Secondary outcomes were time to non-fatal opioid overdose, all-cause mortality, and buprenorphine discontinuation. We defined buprenorphine discontinuation as having a 30-day gap without another prescription following the end date of the previous prescription. We used Cox proportional hazards models to calculate hazards ratios that tested the association between receipt of benzodiazepines and all outcomes, restricted to periods during buprenorphine treatment. FINDINGS Of the 63,389 individuals who received buprenorphine, 24% filled at least one benzodiazepine prescription during buprenorphine treatment. Thirty-one percent of the 183 deaths from opioid overdose occurred when individuals received benzodiazepines during buprenorphine treatment. Benzodiazepine receipt during buprenorphine treatment was associated with an increased risk of fatal opioid overdose adjusted hazard ratio (HR) =3.02; (95% confidence interval [CI], 1.97-4.62), non-fatal opioid overdose, adjusted HR=1.98 (95% CI 1.58-2.48), all-cause mortality, adjusted HR=2.05 (95% CI 1.64-2.55), and a decreased risk of buprenorphine discontinuation, adjusted HR=0.78 (95% CI 0.75-0.80). CONCLUSIONS Benzodiazepine receipt appears to be associated with both increased risk of opioid overdose and all-cause mortality and decreased risk of buprenorphine discontinuation among people receiving buprenorphine.

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在接受丁丙诺啡治疗的人群中，处方苯二氮卓类药物、过量死亡和丁丙诺啡停用之间的关联

背景和目的苯二氮卓类药物通常用于接受丁丙诺啡治疗的阿片类药物使用障碍患者，但可能会增加药物过量的风险。然而，处方苯二氮卓类药物可以通过减少丁丙诺啡的停药来提高护理保留率，从而可以防止非法使用阿片类药物的复发。我们旨在测试苯二氮卓类药物处方与致死性阿片类药物过量、非致死性阿片类药物过量、全因死亡率和丁丙诺啡停用之间的关联。设计和设置 这是一项回顾性队列研究，使用来自美国马萨诸塞州政府机构的 5 个单独关联的数据集。参与者 我们研究了 2012 年 1 月至 2015 年 12 月期间接受丁丙诺啡治疗的 63,389 名 18 岁或以上的马萨诸塞州居民。测量 丁丙诺啡治疗期间填写的苯二氮卓处方是主要的自变量。主要结果是致死性阿片类药物过量的时间。次要结果是发生非致命阿片类药物过量的时间、全因死亡率和丁丙诺啡停用。我们将丁丙诺啡停药定义为在上一次处方结束日期之后没有其他处方的情况下有 30 天的间隔。我们使用 Cox 比例风险模型来计算风险比，以测试苯二氮卓类药物的接受与所有结果之间的关联，仅限于丁丙诺啡治疗期间。结果 在接受丁丙诺啡治疗的 63,389 人中，24% 的人在丁丙诺啡治疗期间至少服用了一种苯二氮卓类处方。在 183 名阿片类药物过量死亡中，有 31% 发生在个人在丁丙诺啡治疗期间接受苯二氮卓类药物治疗时。丁丙诺啡治疗期间接受苯二氮卓类药物与致死性阿片类药物过量的风险增加相关，调整后的风险比 (HR) = 3.02；（95% 置信区间 [CI]，1.97-4.62），非致死性阿片类药物过量，调整后 HR=1.98（95% CI 1.58-2.48），全因死亡率，调整后 HR=2.05（95% CI 1.64-2.55）和丁丙诺啡停药风险降低，调整后的 HR=0.78（95% CI 0.75-0.80）。结论 苯二氮卓类药物的使用似乎与阿片类药物过量风险和全因死亡率的增加以及丁丙诺啡患者停用丁丙诺啡的风险降低有关。丁丙诺啡治疗期间接受苯二氮卓类药物与致死性阿片类药物过量的风险增加相关，调整后的风险比 (HR) = 3.02；（95% 置信区间 [CI]，1.97-4.62），非致死性阿片类药物过量，调整后 HR=1.98（95% CI 1.58-2.48），全因死亡率，调整后 HR=2.05（95% CI 1.64-2.55）和丁丙诺啡停用风险降低，调整后的 HR=0.78（95% CI 0.75-0.80）。结论 接受苯二氮卓类药物似乎与阿片类药物过量和全因死亡率的风险增加有关，并与丁丙诺啡患者停用丁丙诺啡的风险降低有关。丁丙诺啡治疗期间接受苯二氮卓类药物与致死性阿片类药物过量的风险增加相关，调整后的风险比 (HR) = 3.02；（95% 置信区间 [CI]，1.97-4.62），非致死性阿片类药物过量，调整后 HR=1.98（95% CI 1.58-2.48），全因死亡率，调整后 HR=2.05（95% CI 1.64-2.55）和丁丙诺啡停用风险降低，调整后的 HR=0.78（95% CI 0.75-0.80）。结论 苯二氮卓类药物的使用似乎与阿片类药物过量风险和全因死亡率的增加以及丁丙诺啡患者停用丁丙诺啡的风险降低有关。全因死亡率，调整后 HR=2.05（95% CI 1.64-2.55），丁丙诺啡停药风险降低，调整后 HR=0.78（95% CI 0.75-0.80）。结论 苯二氮卓类药物的使用似乎与阿片类药物过量风险和全因死亡率的增加以及丁丙诺啡患者停用丁丙诺啡的风险降低有关。全因死亡率，调整后 HR=2.05（95% CI 1.64-2.55），丁丙诺啡停药风险降低，调整后 HR=0.78（95% CI 0.75-0.80）。结论 苯二氮卓类药物的使用似乎与阿片类药物过量风险和全因死亡率的增加以及丁丙诺啡患者停用丁丙诺啡的风险降低有关。