Efficacy of Transcranial Alternating Current Stimulation for Major Depressive Disorder and the Role of Intensity: A Systematic Review and Exploratory Meta-Analysis.

Authors

Li Qi, Yue Yu, Xiaomin Pan, Jin Li, Zhishun Gao, Ting Zhang, Wenjia Wang, Kai Wang, Qianqian Li, Tongjian Bai

Published in

Alpha psychiatry. Volume 27. Issue 4. Pages 47383. Epub Jul 31, 2026.

Abstract

Current treatments for major depressive disorder (MDD) are limited by efficacy and adverse effects. Transcranial alternating current stimulation (tACS) has emerged as a promising alternative. However, there is still a lack of systematic evaluation of its effectiveness. Recent studies suggest that currents greater than 7 milliamperes (mA) may be necessary to significantly alter potentials in deep brain regions associated with depression. We conducted a systematic review and exploratory meta-analysis to assess the overall efficacy and safety of tACS for MDD and to explore potential associations regarding current intensity by comparing high-intensity tACS (HI-tACS) and low-intensity tACS (LI-tACS) protocols.
A systematic search of Embase, PubMed, Web of Science, the Cochrane Library, ClinicalTrials.gov, and WHO ICTRP was conducted from inception to January 5, 2026. Data were analyzed using a random-effects model, assessing changes in depressive scale scores, response and remission rates, discontinuation, and adverse events.
Randomized controlled trials with 438 participants were included. Compared to sham stimulation, active tACS was associated with a significant reduction in depressive symptoms (moderate effect size). In an exploratory subgroup analysis, HI-tACS was associated with a larger effect size (large effect) than LI-tACS (small effect), with lower heterogeneity observed within subgroups. The HI-tACS group also showed significantly higher response and remission rates. No significant differences in adverse events or treatment discontinuations were observed between the two subgroups.
Our results suggest that tACS may be a potentially effective treatment for MDD. Data from exploratory subgroup analyses provide preliminary, hypothesis-generating evidence that higher intensity may be associated with improved outcomes. However, given the limited evidence base and substantial heterogeneity, as well as the fact that intensity co-varied with stimulation frequency and other parameters in the included trials, these findings do not establish a sole causal link for intensity. Future large-scale, controlled, multi-arm trials are needed to disentangle these factors and confirm these preliminary observations.
The study has been registered on https://www.crd.york.ac.uk/prospero/ (registration number: CRD42024589889; registration link: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024589889).

PMID:
42694614
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

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