Sordo Luis, Barrio Gregorio, Bravo Maria J, Indave B Iciar, Degenhardt Louisa, Wiessing Lucas, Ferri Marica, Pastor-Barriuso Roberto
National Centre for Epidemiology, Carlos III Institute of Health, Madrid, Spain.
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
BMJ. 2017 Apr 26;357:j1550. doi: 10.1136/bmj.j1550.
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. Systematic review and meta-analysis. Medline, Embase, PsycINFO, and LILACS to September 2016. 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. 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. 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. 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.
比较美沙酮或丁丙诺啡替代治疗期间及之后阿片类药物依赖者的全因死亡风险和过量用药死亡风险，并描述治疗开始和停止后死亡风险的趋势。系统评价和荟萃分析。检索截至2016年9月的Medline、Embase、PsycINFO和LILACS数据库。纳入关于阿片类药物依赖者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及之外的随访期内的全因死亡或过量用药死亡情况。两名独立评审员进行数据提取并评估研究质量。通过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非治疗期间的死亡率合并。共有19个符合条件的队列，随访了122885名接受美沙酮治疗1.3至13.9年的患者以及15831名接受丁丙诺啡治疗1.1至4.5年的患者。美沙酮治疗期间和非治疗期间的合并全因死亡率分别为每1000人年11.3例和36.1例（未调整的非治疗期与治疗期死亡率比值为3.20，95%置信区间为2.65至3.86），丁丙诺啡治疗期间和非治疗期间的合并全因死亡率分别降至每1000人年4.3例和9.5例（2.20，1.34至3.61）。在汇总趋势分析中，美沙酮治疗的前四周全因死亡率急剧下降，停止治疗两周后逐渐下降。丁丙诺啡治疗诱导期和其余治疗期间全因死亡率保持稳定。过量用药死亡情况演变相似，美沙酮治疗期间和非治疗期间的汇总过量用药死亡率分别为每1000人年2.6例和12.7例（未调整的非治疗期与治疗期死亡率比值为4.80，2.90至7.96），丁丙诺啡治疗期间和非治疗期间分别为1.4例和4.6例。维持美沙酮和丁丙诺啡治疗与阿片类药物依赖者全因死亡和过量用药死亡风险的大幅降低相关。美沙酮治疗的诱导期以及停止使用这两种药物后的即刻是死亡风险特别增加的时期，公共卫生和临床策略应加以应对以降低此类风险。这些发现可能具有重要意义，但必须进行进一步研究，以适当考虑阿片类药物替代治疗之间死亡率风险比较以及每种治疗期间和非治疗期间潜在的混杂因素和选择偏倚。
