Department of Psychology, City College of New York, New York (Brandt); Division on Substance Use Disorders, New York State Psychiatric Institute, New York (Castillo, Nunes, Luo); Department of Psychiatry, Columbia University Irving Medical Center, New York (Hu, Liu, Nunes, Luo); Department of Biostatistics, Florida International University, Miami (Odom); Division of Biostatistics, Department of Public Health Sciences, University of Miami, Miami (Balise, Feaster).
Am J Psychiatry. 2023 May 1;180(5):386-394. doi: 10.1176/appi.ajp.20220312. Epub 2023 Mar 9.
Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD.
Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models.
By week 24, 39 participants had ≥1 overdose event. The observed frequency of having an overdose event was 15 (5.30%) among 283 patients assigned to naltrexone, eight (1.51%) among 529 patients assigned to methadone, and 16 (1.15%) among 1,387 patients assigned to buprenorphine. Notably, 27.9% of patients assigned to extended-release naltrexone never initiated the medication, and their overdose rate was 8.9% (7/79), compared with 3.9% (8/204) among those who initiated naltrexone. Controlling for sociodemographic and time-varying medication adherence variables and baseline substance use, a proportional hazard model did not show a significant effect of naltrexone assignment. Significantly higher probabilities of experiencing an overdose event were observed among patients with baseline benzodiazepine use (hazard ratio=3.36, 95% CI=1.76, 6.42) and those who either were never inducted on their assigned study medication (hazard ratio=6.64, 95% CI=2.12, 19.54) or stopped their medication after initial induction (hazard ratio=4.04, 95% CI=1.54, 10.65).
Among patients with opioid use disorder seeking medication treatment, the risk of overdose events over the next 24 weeks is elevated among those who fail to initiate or discontinue medication and those who report benzodiazepine use at baseline.
在阿片类药物使用障碍（MOUD）治疗过程中，药物过量的风险尚未明确界定。作者试图通过利用来自三项大型实用 MOUD 临床试验的新数据集来解决这一差距。
对三项试验（N=2199）的不良事件日志（包括药物过量事件）进行了协调，并使用时间依赖性 Cox 比例风险模型对随机分组后 24 周内每个研究组（美沙酮组、纳曲酮组和丁丙诺啡组各一组）的药物过量事件发生风险进行了比较。
在第 24 周时，39 名参与者有≥1 次药物过量事件。观察到的药物过量事件发生率为：纳曲酮组 283 名患者中有 15 例（5.30%），美沙酮组 529 名患者中有 8 例（1.51%），丁丙诺啡组 1387 名患者中有 16 例（1.15%）。值得注意的是，接受延长释放型纳曲酮治疗的患者中有 27.9%从未开始服用药物，其药物过量率为 8.9%（7/79），而开始服用纳曲酮的患者中药物过量率为 3.9%（8/204）。控制社会人口学和随时间变化的药物依从性变量以及基线物质使用情况后，比例风险模型并未显示纳曲酮分配的显著影响。在基线使用苯二氮䓬类药物的患者中（风险比=3.36，95%CI=1.76，6.42）和那些未接受其指定研究药物诱导的患者（风险比=6.64，95%CI=2.12，19.54）或在初始诱导后停止用药的患者（风险比=4.04，95%CI=1.54，10.65）中，药物过量事件发生的可能性显著更高。
在寻求药物治疗的阿片类药物使用障碍患者中，在接下来的 24 周内，那些未能启动或停止用药的患者以及那些在基线时报告使用苯二氮䓬类药物的患者发生药物过量事件的风险更高。
