Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Addiction. 2022 Jul;117(7):1972-1981. doi: 10.1111/add.15862. Epub 2022 Mar 21.
AIMS: To characterize comparative risks and benefits of methadone versus buprenorphine/naloxone in a contemporary cohort where the unregulated drug supply is dominated by fentanyl. DESIGN, SETTING AND PARTICIPANTS: Population-based propensity-score matched cohort study conducted in Ontario, Canada among people aged 18+ initiating opioid agonist therapy (OAT) for an opioid use disorder between October 2016 and December 2018 (n = 18 880). INTERVENTION: Initiation of methadone versus buprenorphine/naloxone. MEASUREMENTS: The primary outcome was opioid overdose (fatal and non-fatal) while on treatment, with secondary outcomes including opioid overdose (first 30 days of treatment), treatment discontinuation, health-care interactions related to treatment of opioid use disorder, receiving a weekly supply of take-home doses and opioid overdose within 30 days of treatment discontinuation. Outcomes were assessed over 1 year. FINDINGS: Overall, 7517 people initiating buprenorphine were matched to an equal number of methadone-treated individuals. Risk of opioid overdose while on treatment [hazard ratio (HR) = 0.50; 95% confidence interval (CI) = 0.37-0.68] or within the first 30 days of treatment (HR = 0.51, 95% CI = 0.31-0.85) was lower among buprenorphine recipients compared to methadone recipients. In secondary analyses, people initiating buprenorphine had a higher risk of treatment discontinuation within the first year (median time to discontinuation 104 versus 265 days, HR = 1.43, 95% CI = 1.37-1.49), had lower rates of health-care interactions for OUD (186.4 versus 254.3 per person-year; rate ratio = 0.73; 95% CI = 0.72-0.75), and a higher rate of receiving weekly take-home doses (HR = 2.33; 95% CI = 2.20-2.46). Overdose rates in the period following OAT discontinuation were higher than those observed while on treatment, but did not differ significantly by OAT type. CONCLUSIONS: Although treatment retention is higher among methadone recipients, overdose risk is also elevated compared to buprenorphine recipients. These findings demonstrate the benefits of any OAT on avoidance of overdose, particularly following treatment discontinuation and with the increasingly unpredictable drug supply in North America.
目的：在当前芬太尼主导的非法药物供应环境下，对美沙酮和丁丙诺啡/纳洛酮的相对风险和益处进行特征描述。
设计、环境和参与者：在加拿大安大略省进行的基于人群的倾向评分匹配队列研究，纳入了 2016 年 10 月至 2018 年 12 月期间因阿片类药物使用障碍接受奥曲肽治疗的 18 岁及以上人群（n=18880）。
干预：美沙酮与丁丙诺啡/纳洛酮的起始治疗。
测量：主要结局是治疗期间的阿片类药物过量（致命和非致命），次要结局包括治疗期间的阿片类药物过量（治疗的前 30 天）、治疗中断、与治疗阿片类药物使用障碍相关的治疗相关的医疗保健互动、接受每周带药回家的剂量以及治疗中断后 30 天内的阿片类药物过量。结果在 1 年内进行评估。
结果：总体而言，有 7517 名接受丁丙诺啡治疗的患者与接受美沙酮治疗的患者数量相等。与美沙酮治疗组相比，接受丁丙诺啡治疗的患者在治疗期间（风险比[HR] = 0.50；95%置信区间[CI] = 0.37-0.68）或治疗的前 30 天（HR = 0.51，95% CI = 0.31-0.85）发生阿片类药物过量的风险较低。在次要分析中，起始接受丁丙诺啡治疗的患者在第一年治疗中断的风险更高（中位数停药时间为 104 天与 265 天，HR=1.43，95% CI=1.37-1.49），接受阿片类药物使用障碍治疗的医疗保健互动率较低（每患者年 186.4 次与 254.3 次；率比[RR]=0.73；95% CI=0.72-0.75），且每周带药回家的比例更高（HR=2.33；95% CI=2.20-2.46）。阿片类药物戒断后期间的过量率高于治疗期间，但与阿片类药物类型无显著差异。
结论：尽管美沙酮治疗组的治疗保留率较高，但与丁丙诺啡治疗组相比，过量风险也较高。这些发现表明任何 OAT 都可以避免过量，尤其是在治疗中断后以及北美日益不可预测的药物供应情况下。
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