抗抑郁药治疗慢性疼痛的不良反应：一项系统评价和荟萃分析。
Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis.
作者信息
Riediger Carina, Schuster Tibor, Barlinn Kristian, Maier Sarah, Weitz Jürgen, Siepmann Timo
机构信息
Department of General, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Germany.
出版信息
Front Neurol. 2017 Jul 14;8:307. doi: 10.3389/fneur.2017.00307. eCollection 2017.
BACKGROUND
Antidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT), there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.
METHODS
Systematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.
RESULTS
Out of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82]) followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.
CONCLUSION
Our synthesized data analysis confirmed overall tolerability of low-dose antidepressants for the treatment of chronic pain and revealed drug specific risk profiles. This encompassing characterization of adverse effect profiles might be useful in defining multimodal treatment regimens for chronic pain which also consider patients' comorbidities and co-medication.
背景
抗抑郁药广泛用于慢性疼痛的治疗。其应用剂量低于产生抗抑郁作用所需的剂量。虽然大型随机对照试验（RCT）已报道抗抑郁药对慢性疼痛的疗效，但关于不良反应和耐受性的数据并不一致。我们旨在综合RCT数据，以探讨抗抑郁药治疗慢性疼痛的不良反应谱和耐受性。
方法
根据系统评价和Meta分析的首选报告项目指南，对不同抗抑郁药治疗慢性疼痛的副作用和安全性进行系统文献研究和Meta分析。检索了美国国立生物技术信息中心图书馆和MEDLINE。随机安慰剂对照试验纳入定量数据合成。
结果
在1975篇筛选的文章中，1995年至2015年发表的33篇论文纳入我们的综述，23项研究纳入Meta分析。除去甲替林外，我们分析中纳入的所有抗抑郁药与安慰剂相比，不良反应风险均更高。最常见的不良反应是口干、头晕、恶心、头痛和便秘。阿米替林、米氮平、地昔帕明、文拉法辛、氟西汀和去甲替林显示出最高的安慰剂效应调整后的不良反应风险。因不良反应而停药的风险在去甲替林中最高（风险比：4.09，95%置信区间[1.31；12.82]），其次是米那普明、文拉法辛和度洛西汀。抗抑郁药治疗下最常见的不良反应是口干、头晕、恶心、头痛和便秘，其次是心悸、出汗和嗜睡。然而，总体耐受性较高。每种抗抑郁药都显示出不同的不良反应风险谱。
结论
我们的综合数据分析证实了低剂量抗抑郁药治疗慢性疼痛的总体耐受性，并揭示了药物特异性风险谱。这种全面的不良反应谱特征可能有助于确定慢性疼痛的多模式治疗方案，该方案也考虑了患者的合并症和联合用药情况。
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