Objective To review interventions to reduce long term opioid treatment in people with chronic non-cancer pain, considering efficacy on dose reduction and discontinuation, pain, function, quality of life, withdrawal symptoms, substance use, and adverse events. Design Systematic review and meta-analysis of randomised controlled trials and non-randomised studies of interventions. Data sources Medline, Embase, PsycINFO, CINAHL, and the Cochrane Library searched from inception to July 2021. Reference lists and previous reviews were also searched and experts were contacted. Eligibility criteria for study selection Original research in English. Case reports and cross sectional studies were excluded. Data extraction and synthesis Two authors independently selected studies, extracted data, and used the Cochrane risk-of-bias tools for randomised and non-randomised studies (RoB 2 and ROBINS-I). Authors grouped interventions into five categories (pain self-management, complementary and alternative medicine, pharmacological and biomedical devices and interventions, opioid replacement treatment, and deprescription methods), estimated pooled effects using random effects meta-analytical models, and appraised the certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). Results Of 166 studies meeting inclusion criteria, 130 (78%) were considered at critical risk of bias and were excluded from the evidence synthesis. Of the 36 included studies, few had comparable treatment arms and sample sizes were generally small. Consequently, the certainty of the evidence was low or very low for more than 90% (41/44) of GRADE outcomes, including for all non-opioid patient outcomes. Despite these limitations, evidence of moderate certainty indicated that interventions to support prescribers’ adherence to guidelines increased the likelihood of patients discontinuing opioid treatment (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1), and that these prescriber interventions as well as pain self-management programmes reduced opioid dose more than controls (intervention v control, mean difference –6.8 mg (standard error 1.6) daily oral morphine equivalent, P<0.001; pain programme v control, −14.31 mg daily oral morphine equivalent, 95% confidence interval −21.57 to −7.05). Conclusions Evidence on the reduction of long term opioid treatment for chronic pain continues to be constrained by poor study methodology. Of particular concern is the lack of evidence relating to possible harms. Agreed standards for designing and reporting studies on the reduction of opioid treatment are urgently needed. Review registration PROSPERO CRD42020140943. See appendices 1-8 for all data available.

中文翻译：

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减少长期阿片类药物治疗慢性非癌症疼痛的干预措施的功效：系统评价和荟萃分析


目的 回顾减少慢性非癌性疼痛患者长期阿片类药物治疗的干预措施，考虑剂量减少和停药、疼痛、功能、生活质量、戒断症状、物质使用和不良事件的疗效。设计 对干预措施的随机对照试验和非随机研究进行系统回顾和荟萃分析。数据来源 Medline、Embase、PsycINFO、CINAHL 和 Cochrane 图书馆检索了从开始到 2021 年 7 月的数据。还检索了参考文献列表和之前的综述，并联系了专家。研究选择的资格标准 用英语进行原创性研究。病例报告和横断面研究被排除在外。数据提取和合成 两位作者独立选择研究、提取数据，并使用 Cochrane 偏倚风险工具进行随机和非随机研究（RoB 2 和 ROBINS-I）。作者将干预措施分为五类（疼痛自我管理、补充和替代医学、药理学和生物医学设备和干预措施、阿片类药物替代治疗和停用方法），使用随机效应荟萃分析模型估计汇总效应，并评估证据的确定性使用 GRADE（建议、评估、制定和评估的分级）。结果 在符合纳入标准的 166 项研究中，130 项（78%）被认为存在严重偏倚风险，并被排除在证据综合之外。在 36 项纳入的研究中，很少有具有可比治疗组的研究，而且样本量通常较小。因此，超过 90% (41/44) 的 GRADE 结果（包括所有非阿片类药物患者的结果）的证据质量较低或非常低。 尽管存在这些局限性，中等质量的证据表明，支持处方者遵守指南的干预措施增加了患者停止阿片类药物治疗的可能性（调整后的比值比 1.5，95% 置信区间 1.0 至 2.1），并且这些处方者干预措施与疼痛自我管理计划比对照减少的阿片类药物剂量更多（干预与对照，平均差 –6.8 mg（标准误差 1.6）每日口服吗啡当量，P<0.001；疼痛计划与对照相比，每日口服吗啡当量 -14.31 mg，95% 置信度区间-21.57至-7.05）。结论 减少长期阿片类药物治疗慢性疼痛的证据仍然受到不良研究方法的限制。特别令人担忧的是缺乏与可能造成的危害相关的证据。迫切需要制定和报告减少阿片类药物治疗研究的商定标准。查看注册 PROSPERO CRD42020140943。有关所有可用数据，请参阅附录 1-8。