Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.
Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.
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DOI：
10.1001/jamapsychiatry.2021.0976
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发表时间：
2021-09-01
期刊：
影响因子：
25.8
通讯作者：
Degenhardt, Louisa
中科院分区：
文献类型：
--
作者：
Santo, Thomas Jr;Clark, Brodie;Degenhardt, Louisa
重要性：阿片类药物依赖者的死亡率高于一般人群。阿片受体激动剂治疗（OAT）是治疗阿片依赖的有效方法；然而，目前还没有关于OAT与具体死亡原因之间关系的系统综述。目的：评估OAT治疗时间与死亡率的关系。数据来源：检索截至2020年2月18日的Embase、MEDLINE和PsycINFO数据库，包括临床试验注册和以前的Cochrane综述。研究选择：所有收集阿片类药物依赖患者在接受和未接受OAT时全因或特定原因死亡率数据的观察性研究均被纳入。随机临床试验（rct）也被纳入。数据提取和综合：本系统评价和荟萃分析遵循系统评价和荟萃分析首选报告项目（PRISMA）指南。提取研究、参与者和治疗特征的数据；计算人年、全因死亡率和特定原因死亡率。采用随机效应荟萃分析汇总粗死亡率和死亡率比（rr）。主要结局和测量：按环境和参与者特征划分的全因死亡率和病因特异性死亡率。特别评价美沙酮和丁丙诺啡OAT。结果：共纳入15项随机对照试验（RCTs） 3852名受试者和36项主要队列研究（primary cohort study） 749名 634名受试者。在队列研究中，OAT期间的全因死亡率是OAT结束期间死亡率的一半以上（RR,0.47; 95% CI, 0.42-0.53）。无论患者的性别、年龄、地理位置、HIV状态、丙型肝炎病毒状态以及是否通过注射服用药物，这种关联都是一致的。美沙酮（RR,0.47; 95% CI, 0.41-0.54）与丁丙诺啡（RR,0.34; 95% CI, 0.26-0.45）的相关性无显著差异。在OAT期间，自杀（RR, 0.48; 95% CI, 0.37-0.61）、癌症（RR, 0.72; 95% CI, 0.52-0.98）、药物相关（RR, 0.41; 95% CI, 0.33-0.52）、酒精相关（RR, 0.59; 95% CI, 0.49-0.72）和心血管相关（RR, 0.69; 95% CI, 0.60-0.79）死亡率的风险较低。在美沙酮治疗的前4周，全因死亡率和药物相关中毒率几乎是OAT治疗剩余时间的两倍（RR, 2.01; 95% CI, 1.55-5.09），但丁丙诺啡组没有这种情况（RR, 0.58; 95% CI, 0.18-1.85）。停止OAT治疗后4周的全因死亡率高出6倍（RR, 6.01; 95% CI, 4.32-8.36），未接受OAT治疗的剩余时间的全因死亡率高出一倍（RR, 1.81; 95% CI, 1.50-2.18）。阿片类激动剂治疗与监禁期间（RR, 0.06; 95% CI, 0.01-0.46）和出狱后较低的死亡率相关（RR, 0.09; 95% CI, 0.02-0.56）。结论和相关性：本系统综述和荟萃分析发现OAT与较低的死亡率相关。然而，获得OAT的机会仍然有限，OAT的覆盖率仍然很低。改善全球可及性的工作可能具有重要的人口层面效益。
Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality.Objective: To estimate the association of time receiving OAT with mortality.Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews.Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included.Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses.Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically.Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR,0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR,0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR,0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56).Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.