Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences (LIM-27) and National Institute of Biomarkers in Neuropsychiatry (INBioN), Department and Institute of Psychiatry, Hospital das Clínicas - HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:105-113. doi: 10.1016/j.pnpbp.2017.10.016. Epub 2017 Oct 28.
Although several studies indicate that placebo response is large to antidepressant pharmacotherapy in major depressive disorder (MDD), no updated meta-analysis has quantified the magnitude of the placebo (sham) response to repetitive transcranial magnetic stimulation (rTMS) in MDD yet.
To conduct a systematic review and meta-analysis on this issue in randomized controlled trials (RCTs) involving participants with MDD; and to explore potential moderators.
PubMed/MEDLINE, Embase, PsycINFO, and Web of Science electronic databases were searched from inception up to March 15, 2017 for RCTs that investigated the efficacy of any rTMS modality compared to sham intervention in participants with acute depressive episodes. Cochrane Risk of Bias Tool was used to estimate risks. We estimated the placebo effect size (Hedges's g, random-effects model) response using placebo groups baseline and endpoint depressive symptom scores. Meta-regressions have been employed to explore potential moderators of response.
Sixty-one studies met eligibility criteria (N=1328; mean age, 47years; 57% females). Placebo response was large (g=0.8, 95% CI=0.65-0.95, p<0.01) regardless of the modality of intervention. Placebo response was directly associated with publication year and depression improvement of the active group, and inversely associated with higher levels of treatment-resistant depression. Other moderators, including gender, age, and stimulator type, were not associated with the outcome. Overall, 24.6%, 67.2%, and 8.2% of studies had an overall low, unclear, and high bias risk, respectively.
Placebo response in rTMS depression trials was large and associated with depression improvement of the active treatment group. Such result suggests that excluding placebo responders with a run-in phase may not confer advantage since response to 'active' rTMS may decrease as well. Moreover, placebo response may be a component of therapeutic response to rTMS in MDD. In addition, placebo response increase over time could indicate improvement in rTMS trial designs, including better sham rTMS methods.
尽管有几项研究表明，在重度抑郁症（MDD）中，安慰剂对抗抑郁药物治疗的反应很大，但尚无更新的荟萃分析量化 MDD 中重复经颅磁刺激（rTMS）的安慰剂（假）反应的幅度。
在涉及 MDD 参与者的随机对照试验（RCT）中对此问题进行系统评价和荟萃分析；并探讨潜在的调节因素。
从建库至 2017 年 3 月 15 日，检索 PubMed/MEDLINE、Embase、PsycINFO 和 Web of Science 电子数据库，以查找比较急性抑郁发作患者任何 rTMS 模式与假干预比较的疗效的 RCT。使用 Cochrane 偏倚风险工具评估风险。我们使用安慰剂组的基线和终点抑郁症状评分来估计安慰剂效应大小（Hedges's g，随机效应模型）。进行了荟萃回归以探讨反应的潜在调节因素。
61 项研究符合入选标准（N=1328；平均年龄 47 岁；57%为女性）。无论干预方式如何，安慰剂反应都很大（g=0.8，95%CI=0.65-0.95，p<0.01）。安慰剂反应与干预的发表年份和活跃组的抑郁改善直接相关，与治疗抵抗性抑郁症的水平升高成反比。其他调节因素，包括性别、年龄和刺激器类型，与结果无关。总体而言，24.6%、67.2%和 8.2%的研究分别具有总体低、不明确和高偏倚风险。
rTMS 抑郁试验中的安慰剂反应很大，与积极治疗组的抑郁改善有关。这样的结果表明，由于“活跃”rTMS 的反应也可能降低，因此排除有预试验的安慰剂反应者可能没有优势。此外，安慰剂反应可能是 MDD 中 rTMS 治疗反应的一个组成部分。此外，随着时间的推移，安慰剂反应的增加可能表明 rTMS 试验设计的改善，包括更好的假 rTMS 方法。
