Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis

Wei Zheng; Dong-Bin Cai; Sha Nie; Jian-Hua Chen; Xing-Bing Huang; Stephan Goerigk; Andre Russowsky Brunoni; Wei Zheng

doi:10.3389/fpsyt.2023.1154354

Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis

Front Psychiatry. 2023 Mar 22:14:1154354. doi: 10.3389/fpsyt.2023.1154354. eCollection 2023.

Authors

Wei Zheng¹, Dong-Bin Cai², Sha Nie³, Jian-Hua Chen³, Xing-Bing Huang³, Stephan Goerigk^{4

5

6}, Andre Russowsky Brunoni^{7

8

9}, Wei Zheng³

Affiliations

¹ Xiamen Xian Yue Hospital, Xiamen, China.
² Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
³ The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
⁴ Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
⁵ Department of Psychological Methodology and Assessment, Ludwig-Maximilians-University, Munich, Germany.
⁶ Department of Psychology, Charlotte Fresenius Hochschule, Munich, Germany.
⁷ Center for Clinical and Epidemiological Research and Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of São Paulo, São Paulo, Brazil.
⁸ Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
⁹ Laboratory of Neuroscience and National Institute of Biomarkers in Psychiatry, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.

Abstract

Objective: We performed a meta-analysis of randomized, double-blind, controlled trials (RCTs) to systematically investigate the therapeutic effects and tolerability of transcranial alternating current stimulation (tACS) for the treatment of patients with major depressive disorder (MDD).

Methods: Electronic search of PubMed, PsycINFO, EMBASE, Chinese National Knowledge Infrastructure, Wanfang database, and the Cochrane Library up to 1 April 2022. Double-blind RCTs examining the efficacy and safety of tACS for patients with MDD were included. The primary outcome was the improvement of depressive symptoms following a course of tACS treatment. Data were analyzed using Review Manager Version 5.3 (Cochrane IMS, Oxford, UK). Study quality was assessed using the Cochrane risk of bias and Jadad scale. Publication bias was assessed using a funnel plot and the Egger test.

Results: We identified 883 articles, of which 4 RCTs with 5 active treatment arms covering 224 participants with MDD on active tACS (n = 117) and sham tACS (n = 107) were eligible for inclusion. Meta-analysis of depressive symptoms at post-tACS found an advantage of active tACS over sham tACS (n = 212, standard mean difference (SMD) = -1.14, 95% confidence interval (CI): -2.23, -0.06; I ² = 90%, P = 0.04). The significant superiority of active tACS over sham tACS in improving depressive symptoms remained in a sensitivity analysis. Active tACS was significantly superior to sham tACS regarding depressive symptoms at the 4 week follow-up (SMD = -1.07, 95% CI: -2.05, -0.08; I ² = 88%, P = 0.03) and study-defined remission [risk ratio (RR) = 2.07, 95% CI: 1.36, 3.14, I ² = 9%, P = 0.0006]. The discontinuation rate due to any reason was similar between the two groups (P > 0.05). All included studies were rated as high quality (Jadad score ≥ 3), with funnel plots of primary outcome not suggestive of publication bias.

Conclusion: tACS appeared to be modestly effective and safe for improving depressive symptoms in patients with MDD, although further studies are warranted.

Keywords: major depressive disorder; meta-analysis; remission; response; transcranial alternating current stimulation (tACS).

Publication types

Systematic Review

Grants and funding

This study was funded by the National Natural Science Foundation of China (82101609), Scientific Research Project of Guangzhou Bureau of Education (202032762), Science and Technology Program Project of Guangzhou (202102020658), Guangzhou Health Science and Technology Project (20211A011045), Guangzhou Science and Technology Project of Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine (20212A011018), China International Medical Exchange Foundation (Z-2018-35-2002), Guangzhou Clinical Characteristic Technology Project (2019TS67), Science and Technology Program Project of Guangzhou (202102020658), and Guangdong Hospital Association (2019ZD06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.