澳大利亚悉尼大学Paul Glare团队对减少长期阿片类药物治疗慢性非癌性疼痛的干预效果进行了系统评价和荟萃分析。相关论文于2022年4月4日发表在《英国医学杂志》上。

该研究旨在评价减少慢性非癌症疼痛患者长期阿片类药物治疗的干预措施，考虑在剂量减少和停药、疼痛、功能、生活质量、戒断症状、药物使用和不良事件方面的疗效。研究人员从MEDLINE、EMBASE和Cochrane图书馆等大型数据库中检索从建库至2021年7月的文献，还搜索了参考列表和之前的评论，并联系专家。

筛选出英语原创研究。排除病例报告和横断面研究。对符合资格的随机对照试验和非随机干预研究进行系统回顾和荟萃分析。由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。

研究人员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、阿片类替代治疗和减压疗法），使用随机效应荟萃分析模型估计汇总效应，并使用等级（建议等级、评估等级、开发等级和评价等级）评估证据的确定性。

在166项符合纳入标准的研究中，130项（78%）被认为存在严重的偏倚风险，并被排除在证据汇总之外。在纳入的36项研究中，几乎没有可比的治疗组，样本量通常较小。因此，超过90%（41/44）的分级结果（包括所有非阿片类患者结果）的证据确定性较低或非常低。

尽管存在这些局限性，但中等确定性的证据表明，支持处方医生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，校正后的优势比1.5；这些处方干预措施以及疼痛自我管理方案比对照组更能减少阿片类药物的剂量（干预组与对照组相比平均每天减少6.8mg口服吗啡当量；疼痛自我管理组与对照组相比平均每天减少14.31mg口服吗啡当量）。

研究结果表明，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学的限制。尤其令人担忧的是，缺乏与潜在危害有关的证据。迫切需要为减少阿片类治疗的研究设计和报告商定标准。

附：英文原文

Title: Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis

Author: Nicholas Avery, Amy G McNeilage, Fiona Stanaway, Claire E Ashton-James, Fiona M Blyth, Rebecca Martin, Ali Gholamrezaei, Paul Glare

Issue&Volume: 2022/04/04

Abstract:

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.

DOI: 10.1136/bmj-2021-066375

Source: https://www.bmj.com/content/377/bmj-2021-066375