National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
Lancet Psychiatry. 2023 Jun;10(6):386-402. doi: 10.1016/S2215-0366(23)00095-0. Epub 2023 May 8.
Opioid dependence is associated with substantial health and social burdens, and opioid agonist treatment (OAT) is highly effective in improving multiple outcomes for people who receive this treatment. Methadone and buprenorphine are common medications provided as OAT. We aimed to examine buprenorphine compared with methadone in the treatment of opioid dependence across a wide range of primary and secondary outcomes.
We did a systematic review and meta-analysis in accordance with GATHER and PRISMA guidelines. We searched Embase, MEDLINE, CENTRAL, and PsycINFO from database inception to Aug 1, 2022; clinical trial registries and previous relevant Cochrane reviews were also reviewed. We included all RCTs and observational studies of adults (aged ≥18 years) with opioid dependence comparing treatment with buprenorphine or methadone. Primary outcomes were retention in treatment at 1, 3, 6, 12, and 24 months, treatment adherence (measured through doses taken as prescribed, dosing visits attended, and biological measures), or extra-medical opioid use (measured by urinalysis and self-report). Secondary outcomes were use of benzodiazepines, cannabis, cocaine, amphetamines, and alcohol; withdrawal; craving; criminal activity and engagement with the criminal justice system; overdose; mental and physical health; sleep; pain; global functioning; suicidality and self-harm; and adverse events. Single-arm cohort studies and RCTs that collected data on buprenorphine retention alone were also reviewed. Data on study, participant, and treatment characteristics were extracted. Study authors were contacted to obtain additional data when required. Comparative estimates were pooled with use of random-effects meta-analyses. The proportion of individuals retained in treatment across multiple timepoints was pooled for each drug. This study is registered with PROSPERO (CRD42020205109).
We identified 32 eligible RCTs (N=5808 participants) and 69 observational studies (N=323 340) comparing buprenorphine and methadone, in addition to 51 RCTs (N=11 644) and 124 observational studies (N=700 035) that reported on treatment retention with buprenorphine. Overall, 61 studies were done in western Europe, 162 in North America, 14 in north Africa and the Middle East, 20 in Australasia, five in southeast Asia, seven in south Asia, two in eastern Europe, three in central Europe, one in east Asia, and one in central Asia. 1 040 827 participants were included in these primary studies; however, gender was only reported for 572 111 participants, of whom 377 991 (66·1%) were male and 194 120 (33·9%) were female. Mean age was 37·1 years (SD 6·0). At timepoints beyond 1 month, retention was better for methadone than for buprenorphine: for example, at 6 months, the pooled effect favoured methadone in RCTs (risk ratio 0·76 [95% CI 0·67-0·85]; I·=74·2%; 16 studies, N=3151) and in observational studies (0·77 [0·68-0·86]; I·=98·5%; 21 studies, N=155 111). Retention was generally higher in RCTs than observational studies. There was no evidence suggesting that adherence to treatment differed with buprenorphine compared with methadone. There was some evidence that extra-medical opioid use was lower in those receiving buprenorphine in RCTs that measured this outcome by urinalysis and reported proportion of positive urine samples (over various time frames; standardised mean difference -0·20 [-0·29 to -0·11]; I·=0·0%; three studies, N=841), but no differences were found when using other measures. Some statistically significant differences were found between buprenorphine and methadone among secondary outcomes. There was evidence of reduced cocaine use, cravings, anxiety, and cardiac dysfunction, as well as increased treatment satisfaction among people receiving buprenorphine compared with methadone; and evidence of reduced hospitalisation and alcohol use in people receiving methadone. These differences in secondary outcomes were based on small numbers of studies (maximum five), and were often not consistent across study types or different measures of the same constructs (eg, cocaine use).
Evidence from trials and observational studies suggest that treatment retention is better for methadone than for sublingual buprenorphine. Comparative evidence on other outcomes examined showed few statistically significant differences and was generally based on small numbers of studies. These findings highlight the imperative for interventions to improve retention, consideration of client-centred factors (such as client preference) when selecting between methadone and buprenorphine, and harmonisation of data collection and reporting to strengthen future syntheses.
Australian National Health and Medical Research Council.
阿片类药物依赖与大量的健康和社会负担有关，而阿片类激动剂治疗（OAT）在改善接受该治疗的人群的多种结局方面非常有效。美沙酮和丁丙诺啡是作为 OAT 提供的常见药物。我们旨在研究丁丙诺啡与美沙酮在广泛的主要和次要结局方面治疗阿片类药物依赖的效果。
我们根据 GATHER 和 PRISMA 指南进行了系统评价和荟萃分析。我们从数据库建立到 2022 年 8 月 1 日，在 Embase、MEDLINE、CENTRAL 和 PsycINFO 中进行了搜索；还审查了临床试验注册处和之前的相关 Cochrane 综述。我们纳入了所有比较丁丙诺啡或美沙酮治疗阿片类药物依赖的成人（年龄≥18 岁）的 RCT 和观察性研究。主要结局是在 1、3、6、12 和 24 个月时的治疗保留率、治疗依从性（通过规定剂量的服用、就诊次数和生物测量来衡量）或额外的阿片类药物使用（通过尿液分析和自我报告来衡量）。次要结局是使用苯二氮䓬类药物、大麻、可卡因、苯丙胺和酒精；戒断；渴望；犯罪活动和与刑事司法系统的接触；过量；心理健康；睡眠；疼痛；整体功能；自杀意念和自残；以及不良事件。还审查了仅收集丁丙诺啡保留数据的单臂队列研究和 RCT。提取研究、参与者和治疗特征的数据。当需要时，联系研究作者以获取额外数据。使用随机效应荟萃分析汇总了具有可比性的估计值。对于每种药物，都汇总了在多个时间点保留在治疗中的个体比例。这项研究已在 PROSPERO（CRD42020205109）上注册。
我们确定了 32 项符合条件的 RCT（N=5808 名参与者）和 69 项观察性研究（N=323340）比较丁丙诺啡和美沙酮，此外还有 51 项 RCT（N=11644 名参与者）和 124 项观察性研究（N=700035）报告了丁丙诺啡的治疗保留情况。总体而言，61 项研究在西欧进行，162 项在北美进行，14 项在北非和中东进行，20 项在澳大拉西亚进行，5 项在东南亚进行，7 项在南亚进行，2 项在东欧进行，3 项在中欧进行，1 项在东亚进行，1 项在中亚进行。这些主要研究纳入了 1040827 名参与者；然而，只有 572111 名参与者报告了性别，其中 377991（66.1%）名男性和 194120（33.9%）名女性。平均年龄为 37.1 岁（SD 6.0）。在 1 个月以上的时间点，美沙酮的保留率优于丁丙诺啡：例如，在 RCT 中，6 个月时，风险比有利于美沙酮（0.76 [95%CI 0.67-0.85]；I²=74.2%；16 项研究，N=3151），在观察性研究中，风险比也有利于美沙酮（0.77 [0.68-0.86]；I²=98.5%；21 项研究，N=155111）。RCT 中的保留率通常高于观察性研究。没有证据表明丁丙诺啡与美沙酮相比，治疗依从性存在差异。有一些证据表明，接受丁丙诺啡治疗的人尿液中转录分析和报告阳性尿液样本比例（在不同时间范围内）的额外阿片类药物使用较少（标准均数差-0.20 [-0.29 至-0.11]；I²=0.0%；三项研究，N=841），但使用其他措施时未发现差异。在一些次要结局方面，丁丙诺啡和美沙酮之间存在一些统计学上显著的差异。接受丁丙诺啡治疗的人可卡因使用、渴望、焦虑和心脏功能障碍减少，治疗满意度增加；接受美沙酮治疗的人住院和酒精使用减少。这些次要结局的差异基于数量有限的研究（最多五项），并且通常在研究类型或相同结构的不同措施之间不一致（例如，可卡因使用）。
来自试验和观察性研究的证据表明，美沙酮的治疗保留率优于丁丙诺啡。对检查的其他结局的比较证据显示，差异很小，且通常基于数量有限的研究。这些发现强调了加强干预措施以提高保留率、在选择美沙酮和丁丙诺啡时考虑以客户为中心的因素（例如客户偏好）以及协调数据收集和报告以加强未来综合分析的必要性。
澳大利亚国家卫生和医学研究理事会。
