Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study
Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study
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DOI：
10.1016/s2215-0366(15)00366-1
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发表时间：
2015-10-01
影响因子：
64.3
通讯作者：
Degenhardt, Louisa
中科院分区：
文献类型：
--
作者：
Kimber, Jo;Larney, Sarah;Degenhardt, Louisa
背景阿片类药物依赖增加过早死亡的风险。使用美沙酮或丁丙诺啡的阿片类药物替代疗法可降低死亡风险，尤其是药物相关过量。临床指南推荐美沙酮作为阿片类药物替代治疗的第一线。我们的目的是通过比较治疗诱导时、治疗中药物转换后和治疗停止后的全因死亡率和药物相关过量死亡率，来测试丁丙诺啡治疗是否比美沙酮治疗具有更低的死亡风险。（n=32 033），来自澳大利亚新南威尔士州，从2001年8月1日至2010年12月31日开始接受美沙酮或丁丙诺啡治疗，包括190 232.6人-年的随访。我们比较了全因和药物相关过量死亡的粗死亡率（CMR），以及根据年龄、性别、治疗期间或治疗结束时间、药物类型、结果：与美沙酮组相比，在治疗的前4周内，开始使用丁丙诺啡的患者的全因死亡率和药物相关死亡率降低（校正的全因MRR 2.17，95% CI 1.29-3.67;校正的药物相关MRR 4.88，1.73-13.69）。对于剩余的治疗时间，药物相关死亡风险没有差异（校正的MRR 1.18，95% CI 0.89-1.56），但弱证据表明丁丙诺啡的全因死亡率低于美沙酮（1.66，1.40-1.96）。在治疗停止后的4周内，全因死亡率没有差异，但美沙酮的药物相关死亡率较低（校正的全因MRR 1.12，0.79-1.59;校正的药物相关MRR 0.50，0.29-0.86）。在治疗期间从丁丙诺啡转换为美沙酮的患者在美沙酮治疗的前4周内的死亡率低于仅接受美沙酮治疗的匹配对照组（CMR差异7.1/1000人-年，95% CI 0.1-14.0）;从丁丙诺啡转换为美沙酮或转换为任何一种药物超过前4周的死亡率没有差异。解释在阿片样物质替代疗法的前4周中具有高死亡风险的环境中，丁丙诺啡似乎降低了这一时期的死亡率，但此后或对于药物的治疗中转换，注意到丁丙诺啡和美沙酮之间几乎没有差异。我们的研究结果和进一步评估的阶梯式治疗模式的跨队列确证是必要的。
Background Opioid dependence increases risk of premature mortality. Opioid substitution therapy with methadone or buprenorphine reduces mortality risk, especially for drug-related overdose. Clinical guidelines recommend methadone as the first line of opioid substitution therapy. We aimed to test whether buprenorphine treatment has a lower mortality risk than does methadone treatment by comparing all-cause mortality and drug-related overdose mortality at treatment induction, after in-treatment medication switches, and following treatment cessation.Methods We did a retrospective cohort study of all patients with opioid dependency (n=32 033) in New South Wales, Australia, who started a methadone or buprenorphine treatment episode from Aug 1, 2001, to Dec 31, 2010, including 190 232.6 person-years of follow-up. We compared crude mortality rates (CMRs) for all-cause and drug-related overdose mortality, and mortality rate ratios (MRRs) according to age, sex, period in or out of treatment, medication type, and in-treatment switching.Findings Patients who initiated with buprenorphine had reduced all-cause and drug-related mortality during the first 4 weeks of treatment compared with those who initiated with methadone (adjusted all-cause MRR 2.17, 95% CI 1.29-3.67; adjusted drug-related MRR 4.88, 1.73-13.69). For the remaining time on treatment, drug-related mortality risk did not differ (adjusted MRR 1.18, 95% CI 0.89-1.56), but weak evidence suggested that all-cause mortality was lower for buprenorphine than methadone (1.66, 1.40-1.96). In the 4 weeks after treatment cessation, all-cause mortality did not differ, but drug-related mortality was lower for methadone (adjusted all-cause MRR 1.12, 0.79-1.59; adjusted drug-related MRR 0.50, 0.29-0.86). Patients who switched from buprenorphine to methadone during treatment had lower mortality in the first 4 weeks of methadone treatment than matched controls who received methadone only (CMR difference 7.1 per 1000 person-years, 95% CI 0.1-14.0); no mortality difference was noted for switches from buprenorphine to methadone or for switches to either medication beyond the first 4 weeks of treatment.Interpretation In a setting with high risk of death in the first 4 weeks of opioid substitution therapy, buprenorphine seemed to reduce mortality in this period, but little difference between buprenorphine and methadone was noted thereafter or for in-treatment switching of medications. Cross-cohort corroboration of our findings and further assessment of the stepped treatment model is warranted.