Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.
Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.
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DOI：
10.1136/bmj.j1550
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发表时间：
2017-04-26
期刊：
影响因子：
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通讯作者：
Pastor-Barriuso R
中科院分区：
文献类型：
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作者：
Sordo L;Barrio G;Bravo MJ;Indave BI;Degenhardt L;Wiessing L;Ferri M;Pastor-Barriuso R
目的比较阿片类药物依赖者在美沙酮或丁丙诺啡替代治疗期间和之后的全因死亡率和过量死亡率的风险，并分析开始和停止治疗后死亡率风险的趋势。 设计：系统综述和荟萃分析。 数据来源Medline、Embase、PsycINFO和LILACS，截至2016年9月。 研究选择在阿片类药物依赖者中进行的前瞻性或回顾性队列研究，这些研究报告了在美沙酮或丁丙诺啡阿片类药物替代治疗期间和之后的随访期间因各种原因或过量而死亡。 数据提取和综合两名独立的审查员进行数据提取和评估研究质量。通过使用多变量随机效应荟萃分析，将美沙酮或丁丙诺啡队列中治疗期间和治疗结束时的死亡率合并。 结果有19个合格队列，随访122 885人接受美沙酮治疗1.3-13.9年，15 831人接受丁丙诺啡治疗1.1-4.5年。美沙酮治疗组和非美沙酮治疗组的合并全因死亡率分别为11.3和36.1/1000人年（未校正的外出率比为3.20，95%置信区间为2.65至3.86），丁丙诺啡治疗组和非丁丙诺啡治疗组的合并全因死亡率分别为4.3和9.5（2.20，1.34至3.61）。在汇总趋势分析中，全因死亡率在美沙酮治疗的前四周急剧下降，并在离开治疗后两周逐渐下降。在诱导期间和丁丙诺啡治疗的剩余时间内，全因死亡率保持稳定。过量死亡率的演变类似，美沙酮治疗前后的合并过量死亡率为2.6和12.7/1000人年（未校正的外-内率比为4.80，2.90 - 7.96），丁丙诺啡治疗前后的合并过量死亡率为1.4和4.6。 结论：美沙酮和丁丙诺啡治疗的保留与阿片类药物依赖者全因和过量死亡风险的大幅降低相关。美沙酮治疗的诱导阶段和两种药物治疗结束后立即离开的时间是死亡风险特别增加的时期，应通过公共卫生和临床策略来减轻这种风险。这些发现可能很重要，但必须进行进一步的研究，以适当解释阿片类药物替代治疗之间以及每次治疗前后死亡风险比较中的潜在混杂和选择偏倚。
Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, and LILACS to September 2016. Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.