Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder: A Systematic Review and Network Meta-Analysis

IF 4.7 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Evidence‐Based Medicine Pub Date : 2026-09-25 Epub Date: 2026-07-01 DOI:10.1111/jebm.70155

Yue Zhang, Jinyang Meng, Xiaobo Liu, Hong Tang, Dongling Zhong, Yuxi Li, Jialin Li, Juan Li, Yongxin Cui, Anren Zhang, Chen Xue, Rongjiang Jin

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引用次数: 0

Abstract

Objective

This systematic review and network meta-analysis (NMA) aimed to compare and rank the efficacy and acceptability of different repetitive transcranial magnetic stimulation (rTMS) modalities for major depressive disorder (MDD).

Methods

The following databases were searched from inception to October 8, 2025: PubMed, Embase, the Cochrane Library, Web of Science, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang Database. In order to identify relevant unpublished studies and ongoing clinical trials, gray literature and trial registries were examined. The randomized controlled trials that investigated the effect of rTMS interventions for MDD were included. We included studies involving adults (aged ≥ 18 years) with a clinical diagnosis of unipolar MDD, which utilized at least two of the following rTMS modalities: low-frequency left (LFL-) rTMS, high-frequency left (HFL-) rTMS, low-frequency right (LFR-) rTMS, high-frequency right (HFR-) rTMS, bilateral (BL-) rTMS, deep TMS (dTMS), theta burst stimulation (TBS), accelerated rTMS (aTMS), synchronized TMS (sTMS), or sham stimulation. The primary endpoints were efficacy (response rate) and acceptability (dropout rate). Additionally, the symptom remission rate was assessed as a secondary outcome. Two authors independently completed the article selection and data extraction. We also evaluated the risk of bias in the included studies with the Cochrane ROB 2.0 tool. The certainty of evidence for each outcome was assessed using the Confidence in Network Meta-Analysis (CINeMA) framework. A conventional pairwise meta-analysis was performed using RevMan software. A NMA was performed with Markov chain Monte Carlo simulations to facilitate indirect comparisons across different rTMS modalities. We applied funnel plots to examine publication bias and assessed the robustness of our findings through sensitivity analysis and subgroup analysis.

Results

A total of 141 trials comprising 10,587 participants with MDD were included. The aTMS (odds ratio [OR]: 4.14; 95% confidence interval [CI] 2.14, 8.01), TBS (OR: 4.47; 95% CI, 3.13, 6.37), BL (OR: 3.93; 95% CI, 2.56, 6.03), HFL (OR: 3.34; 95% CI, 2.80, 3.98), LFR (OR: 2.90; 95% CI, 2.13, 3.95) demonstrated significantly greater efficacy than sham control. Additionally, aTMS (OR: 4.44; 95% CI, 1.02, 19.29), TBS (OR: 4.78; 95% CI, 1.23, 18.62), BL (OR: 4.21; 95% CI, 1.06, 16.71) also showed superior efficacy compared to LFL. Furthermore, sTMS was less effective than TBS (OR: 0.27; 95% CI, 0.08, 0.94). In terms of achieving remission, TBS (OR: 4.81; 95% CI, 2.59, 8.95), BL (OR: 4.69; 95% CI, 2.27, 9.69), HFL (OR: 3.35; 95% CI, 2.34, 4.81), and LFR (OR: 3.27; 95% CI, 1.48, 7.24) were all significantly superior to sham control. The estimated relative ranking of treatments suggested that TBS (87.2%) might be the most efficacious among all rTMS modalities. The surface under the cumulative ranking curve (SUCRA) probabilities for acceptability were as follows: BL (80.1%), dTMS (78.1%), LFR (62.8%), HFL (56.5%), sham (50.0%), TBS (49.9%), sTMS (34.0%), aTMS (28.3%), LFL (10.4%). Our sensitivity analysis excluding high-risk studies yielded largely consistent results with the primary analysis. In particular, the superiority of TBS over sham stimulation remained stable. Although the effect sizes were slightly reduced, the estimates remained statistically significant. In the treatment-resistant depression (TRD) subgroup, TBS demonstrated the highest probability of response (SUCRA: 87.5%) and remission (SUCRA: 79.2%), with efficacy significantly superior to sham stimulation. In the non-TRD subgroup, aTMS ranked best for response rate (SUCRA: 83.0%), while LFR achieved the highest remission rate (SUCRA: 81.5%; OR: 7.16). No significant differences in acceptability were observed between any active intervention and sham across all subgroups. The risk-of-bias assessment categorized 87 studies as high risk, 51 as having some concerns, and only three as low risk. CINeMA results showed that the comparison of BL versus sham had moderate confidence for remission rate, while other comparisons for response, remission, and acceptability were largely rated as low or very low confidence.

Conclusions

TBS had the highest probability of being the most effective rTMS modality for depression, but the confidence intervals overlapped across multiple comparisons, and the effect sizes were modest. High-quality head-to-head trials are needed to confirm these probabilistic rankings.

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重复经颅磁刺激治疗重度抑郁症：系统回顾和网络荟萃分析。

目的：本系统综述和网络荟萃分析（NMA）旨在比较不同重复经颅磁刺激（rTMS）治疗重度抑郁症（MDD）的疗效和可接受性。方法：检索自建库至2025年10月8日的数据库：PubMed、Embase、Cochrane图书馆、Web of Science、中国生物医学数据库（CBM）、中国知网（CNKI）、中国科技期刊库（VIP）、万方数据库。为了确定相关的未发表的研究和正在进行的临床试验，我们检查了灰色文献和试验注册。研究rTMS干预治疗重度抑郁症效果的随机对照试验被纳入。我们纳入了临床诊断为单极重度抑郁症的成年人（年龄≥18岁）的研究，这些研究至少使用了以下两种rTMS方式：低频左（LFL-） rTMS、高频左（HFL-） rTMS、低频右（LFR-） rTMS、高频右（HFR-） rTMS、双侧（BL-） rTMS、深度TMS （dTMS）、θ波脉冲刺激（TBS）、加速rTMS （aTMS）、同步TMS （sTMS）或假刺激。主要终点是疗效（有效率）和可接受性（辍学率）。此外，症状缓解率作为次要结果进行评估。两位作者独立完成文章选择和数据提取。我们还使用Cochrane ROB 2.0工具评估纳入研究的偏倚风险。使用网络荟萃分析（CINeMA）框架评估每个结果证据的确定性。采用RevMan软件进行常规两两元分析。通过马尔可夫链蒙特卡罗模拟进行NMA，以促进不同rTMS模式之间的间接比较。我们应用漏斗图检查发表偏倚，并通过敏感性分析和亚组分析评估我们发现的稳健性。结果：共纳入141项试验，包括10587名重度抑郁症患者。aTMS（优势比[OR]: 4.14； 95%可信区间[CI] 2.14, 8.01）、TBS （OR: 4.47; 95% CI, 3.13, 6.37）、BL （OR: 3.93; 95% CI, 2.56, 6.03）、HFL （OR: 3.34; 95% CI, 2.80, 3.98）、LFR （OR: 2.90; 95% CI, 2.13, 3.95）的疗效显著高于假对照组。此外，aTMS （OR: 4.44; 95% CI, 1.02, 19.29）、TBS （OR: 4.78; 95% CI, 1.23, 18.62）、BL （OR: 4.21; 95% CI, 1.06, 16.71）也显示出优于LFL的疗效。此外，sTMS的疗效低于TBS （OR: 0.27; 95% CI, 0.08, 0.94）。就实现缓解而言，TBS （OR: 4.81; 95% CI, 2.59, 8.95）、BL （OR: 4.69; 95% CI, 2.27, 9.69）、HFL （OR: 3.35; 95% CI, 2.34, 4.81）和LFR （OR: 3.27; 95% CI, 1.48, 7.24）均显著优于假对照组。估计的相对治疗排名表明，TBS（87.2%）可能是所有rTMS方式中最有效的。累积排序曲线下面（SUCRA）可接受概率依次为：BL（80.1%）、dTMS（78.1%）、LFR（62.8%）、HFL（56.5%）、sham（50.0%）、TBS（49.9%）、sTMS（34.0%）、aTMS（28.3%）、LFL（10.4%）。我们的敏感性分析排除了高风险研究，结果与初步分析基本一致。特别是，TBS相对于假刺激的优势保持稳定。虽然效应量略有减少，但估计结果在统计上仍然显著。在难治性抑郁症（TRD）亚组中，TBS表现出最高的缓解概率（SUCRA: 87.5%）和缓解概率（SUCRA: 79.2%），其疗效显著优于假刺激。在非trd亚组中，aTMS的缓解率最高（SUCRA: 83.0%），而LFR的缓解率最高（SUCRA: 81.5%; OR: 7.16）。在所有亚组中，积极干预和假干预的可接受性没有显著差异。风险偏倚评估将87项研究归为高风险，51项为有一定顾虑，只有3项为低风险。CINeMA结果显示，BL与sham在缓解率方面的比较具有中等置信度，而其他在反应、缓解和可接受性方面的比较大多被评为低置信度或极低置信度。结论：TBS最有可能成为治疗抑郁症最有效的rTMS方式，但在多个比较中置信区间重叠，效应量适中。需要高质量的正面试验来证实这些概率排名。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Evidence‐Based Medicine MEDICINE, GENERAL & INTERNAL-

CiteScore

11.20

自引率

1.40%

发文量

期刊介绍： The Journal of Evidence-Based Medicine (EMB) is an esteemed international healthcare and medical decision-making journal, dedicated to publishing groundbreaking research outcomes in evidence-based decision-making, research, practice, and education. Serving as the official English-language journal of the Cochrane China Centre and West China Hospital of Sichuan University, we eagerly welcome editorials, commentaries, and systematic reviews encompassing various topics such as clinical trials, policy, drug and patient safety, education, and knowledge translation.