抗抑郁药治疗背痛和骨关节炎的疗效和安全性：系统评价和荟萃分析。

OBJECTIVE: To investigate the efficacy and safety of antidepressants for back and osteoarthritis pain compared with placebo. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, CINAHL, International Pharmaceutical Abstracts, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to 15 November and updated on 12 May 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials comparing the efficacy or safety, or both of any antidepressant drug with placebo (active or inert) in participants with low back or neck pain, sciatica, or hip or knee osteoarthritis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Pain and disability were primary outcomes. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst pain or disability). A random effects model was used to calculate weighted mean differences and 95% confidence intervals. Safety (any adverse event, serious adverse events, and proportion of participants who withdrew from trials owing to adverse events) was a secondary outcome. Risk of bias was assessed with the Cochrane Collaboration's tool and certainty of evidence with the grading of recommendations assessment, development and evaluation (GRADE) framework. RESULTS: 33 trials (5318 participants) were included. Moderate certainty evidence showed that serotonin-noradrenaline reuptake inhibitors (SNRIs) reduced back pain (mean difference -5.30, 95% confidence interval -7.31 to -3.30) at 3-13 weeks and low certainty evidence that SNRIs reduced osteoarthritis pain (-9.72, -12.75 to -6.69) at 3-13 weeks. Very low certainty evidence showed that SNRIs reduced sciatica at two weeks or less (-18.60, -31.87 to -5.33) but not at 3-13 weeks (-17.50, -42.90 to 7.89). Low to very low certainty evidence showed that tricyclic antidepressants (TCAs) did not reduce sciatica at two weeks or less (-7.55, -18.25 to 3.15) but did at 3-13 weeks (-15.95, -31.52 to -0.39) and 3-12 months (-27.0, -36.11 to -17.89). Moderate certainty evidence showed that SNRIs reduced disability from back pain at 3-13 weeks (-3.55, -5.22 to -1.88) and disability due to osteoarthritis at two weeks or less (-5.10, -7.31 to -2.89), with low certainty evidence at 3-13 weeks (-6.07, -8.13 to -4.02). TCAs and other antidepressants did not reduce pain or disability from back pain. CONCLUSION: Moderate certainty evidence shows that the effect of SNRIs on pain and disability scores is small and not clinically important for back pain, but a clinically important effect cannot be excluded for osteoarthritis. TCAs and SNRIs might be effective for sciatica, but the certainty of evidence ranged from low to very low. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020158521.

目的：评估抗抑郁药治疗腰痛和骨关节炎疼痛的疗效和安全性，与安慰剂相比。

设计：系统评价和荟萃分析。

数据来源：Medline、Embase、Cochrane 对照试验中心注册库、CINAHL、国际药学文摘、ClinicalTrials.gov 和世界卫生组织国际临床试验注册平台，从成立到 2020 年 11 月 15 日，并于 2020 年 5 月 12 日更新。

纳入研究的选择标准：比较任何抗抑郁药与安慰剂（活性或惰性）在腰痛、颈痛、坐骨神经痛、髋或膝骨关节炎患者中的疗效或安全性，或两者兼有的随机对照试验。

数据提取和综合：两名独立审查员提取数据。疼痛和残疾是主要结局。疼痛和残疾评分转换为 0（无疼痛或残疾）至 100（最疼痛或残疾）的量表。使用随机效应模型计算加权均数差异和 95%置信区间。安全性（任何不良事件、严重不良事件以及因不良事件退出试验的参与者比例）是次要结局。使用 Cochrane 协作工具评估偏倚风险，使用推荐评估、制定和评价（GRADE）框架评估证据确定性。

结果：纳入 33 项试验（5318 名参与者）。中度确定性证据表明，选择性 5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）可减少腰痛（平均差异-5.30，95%置信区间-7.31 至-3.30）在 3-13 周，低确定性证据表明 SNRIs 可减少骨关节炎疼痛（-9.72，-12.75 至-6.69）在 3-13 周。非常低确定性证据表明，SNRIs 可在两周或更短时间内减少坐骨神经痛（-18.60，-31.87 至-5.33），但在 3-13 周内无效果（-17.50，-42.90 至 7.89）。低至非常低确定性证据表明三环类抗抑郁药（TCAs）在两周或更短时间内不能减少坐骨神经痛（-7.55，-18.25 至 3.15），但在 3-13 周（-15.95，-31.52 至-0.39）和 3-12 个月（-27.0，-36.11 至-17.89）时有效。中度确定性证据表明，SNRIs 可减少腰痛（3-13 周）（-3.55，-5.22 至-1.88）和骨关节炎引起的残疾（3-13 周）（-5.10，-7.31 至-2.89），低确定性证据在 3-13 周内（-6.07，-8.13 至-4.02）。TCAs 和其他抗抑郁药不能减轻腰痛或残疾。

结论：中度确定性证据表明，SNRIs 对疼痛和残疾评分的影响较小，对腰痛的临床意义不大，但对骨关节炎的临床意义不能排除。TCAs 和 SNRIs 可能对坐骨神经痛有效，但证据的确定性从低到非常低。

系统评价注册：PROSPERO CRD42020158521。