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Meta-Analysis
. 2025 Jun 2;8(6):e2516459.
doi: 10.1001/jamanetworkopen.2025.16459.

Transcranial Electrical Stimulation in Treatment of Depression: A Systematic Review and Meta-Analysis

Caili Ren  1   2 , Sandeep R Pagali  3 , Zhen Wang  4 , Simon Kung  1 , Renu Bhargavi Boyapati  5   6 , Karimul Islam  5 , John W Li  1 , K Maureen Shelton  1 , Anne Waniger  1 , Ann M Rydberg  1 , Leslie C Hassett  7 , Paul E Croarkin  1 , Brian N Lundstrom  8 , Alvaro Pascual-Leone  9   10 , Maria I Lapid  1
Affiliations
Meta-Analysis

Transcranial Electrical Stimulation in Treatment of Depression: A Systematic Review and Meta-Analysis

Caili Ren et al. JAMA Netw Open. .

Abstract

Importance: The role and safety of transcranial electrical stimulation (tES) for treating depressive disorders remain under evaluation.

Objective: To evaluate tES treatment in patients with major depressive disorder (MDD) and comorbid depressive conditions.

Data sources: A search of MEDLINE, Embase, Cochrane, APA PsycINFO, and Scopus databases was conducted from inception to September 17, 2024.

Study selection: Randomized clinical trials (RCTs) of adults with MDD, depression with psychiatric comorbidities (DPC), or depression with medical comorbidities (DMC), treated with transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or transcranial random noise stimulation (tRNS), compared with sham or other treatments were included.

Data extraction and synthesis: Independent reviewers extracted data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, with random-effects meta-analysis used for pooling.

Main outcomes and measures: Primary outcomes were depression severity, response and remission rates, and adverse events. Standardized mean differences (SMDs) were reported for continuous outcomes, and odds ratios (ORs) were reported for categorical outcomes. Quality of evidence (QOE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria.

Results: The meta-analysis included 5522 participants from 114 study groups from 88 RCTs (3198 female [58.9%]; mean [range] age, 43.1 [19.4-76.9] years). Most studies (104 study groups from 79 RCTs [91.2%]) evaluated tDCS, while 7 study groups from 6 RCTs (6.1%) evaluated tACS, and 3 study groups from 3 RCTs (2.7%) evaluated tRNS. tES was associated with reduced depressive symptoms (SMD = -0.59; 95% CI, -0.83 to -0.35; low QOE) and improvement in DMC (SMD = -1.05; 95% CI, -1.67 to -0.43; low QOE) and DPC (SMD = -0.78; 95% CI, -1.27 to -0.29; low QOE) compared with MDD (SMD = -0.22; 95% CI, -0.44 to 0.01; low QOE). tDCS was associated with reduced depression in DMC (SMD = -1.05; 95% CI, -1.70 to -0.40; very low QOE) and DPC (SMD = -0.88; 95% CI, -1.40 to -0.36; low QOE) but not MDD. tACS was associated with improved MDD symptoms (SMD = -0.58; 95% CI, -0.96 to -0.20; high QOE) and response rates (OR, 2.07; 95% CI, 1.34 to 3.19; high QOE). Combined tDCS and medication was associated with reduced symptoms (SMD = -0.51; 95% CI, -0.90 to -0.13; moderate QOE) and increased response (OR, 2.25; 95% CI, 1.08 to 4.65; high QOE) in MDD. tDCS combined with psychotherapy was not associated with improvement. Subgroup analysis showed that anodal left dorsolateral prefrontal cortex DCS was associated with improved outcomes. Mild to moderate adverse events were more frequent in tES groups.

Conclusions and relevance: In this systematic review and meta-analysis, tDCS was associated with improvement in depression among patients with DMC and DPC (with smaller benefits in MDD), tACS was associated with improved MDD outcomes (while tRNS had insufficient evidence) in smaller samples, and combined tDCS and medication was associated with improvement in depression. These findings suggest that tES is well-tolerated overall, with only mild to moderate adverse events, and that future research should optimize stimulation parameters and individualize tES interventions.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Pagali reported receiving grants from the Mayo Clinic (small grants grant No. UL1TR002377) and the National Center for Advancing Translational Sciences, a component of the National Institutes of Health (NIH) outside the submitted work. Dr Croarkin reported being a principal investigator at Innosphere in a multicenter supported trial and receiving in-kind equipment support from MagVenture for an NIH-funded study outside the submitted work. Dr Lundstrom reported having intellectual property licensed to Cadence Neuroscience Inc (all contractual rights waived; all funds to Mayo Clinic); being a site investigator for the Medtronic Epilepsy Post-Approval Study, Neuroelectrics Transcranial Direct Current Stimulation for Epilepsy Study, and Rapport Therapeutics; being an industry consultant for Epiminder and Medtronic (all funds to Mayo Clinic), and providing educational support for Dixi Medical outside the submitted work. Dr Pascual-Leone reported being a paid member of scientific advisory boards for Neuroelectrics, AscenZion, and Magstim; receiving grants from the NIH (grant No. R01AG076708), Jack Satter Foundation, and BrightFocus Foundation; and being a co-founder of TI solutions and co-founder and chief medical officer of Linus Health outside the submitted work. Dr. Pascual-Leone is also listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging, and applications of noninvasive brain stimulation in various neurological disorders, as well as digital biomarkers of cognition and digital assessments for early diagnosis of dementia. Dr Lapid reported serving on the scientific advisory board of PurMinds Neuropharma, with the potential for future royalties, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Studies
Figure 2.
Figure 2.. Pooled Effect Size and Quality of Evidence for Primary Depression Symptoms
No studies were available for the following comparisons: (1) transcranial alternating current stimulation (tACS) vs sham in the depression with medical comorbidities (DMC) group and (2) transcranial random noise stimulation (tRNS) vs sham in the depression with psychiatric comorbidities (DPC) group. Studies included are listed in eTable 4 in Supplement 1. Other brain stimulation (OBS) techniques include electroconvulsive therapy, cranial electrotherapy stimulation, and repetitive transcranial magnetic stimulation. Pharmacotherapy indicates treatment involving additional medications (eg, methadone or naltrexone). MDD indicates major depressive disorder; NA, not applicable; SMD, standard mean difference; tDCS, transcranial direct current stimulation; tES, transcranial electrical stimulation.
Figure 3.
Figure 3.. Pooled Effect Size and Quality of Evidence for Treatment Response and Remission
Studies included are listed in eTable 5 in Supplement 1. Other brain stimulation (OBS) techniques include electroconvulsive therapy, cranial electrotherapy stimulation, and repetitive transcranial magnetic stimulation. DMC indicates depression with medical comorbidities; DPC, depression with psychiatric comorbidities; MDD, major depressive disorder; NA, not applicable; OR, odds ratio; tACS, transcranial alternating current stimulation; tDCS, transcranial direct current stimulation; tES, transcranial electrical stimulation; tRNS, transcranial random noise stimulation.
Figure 4.
Figure 4.. Transcranial Electrical Stimulation Compared With Sham Across Diagnostic Groups
Standardized mean differences (SMDs) and 95% CIs are reported in eTable 4 in Supplement 1. DMC indicates depression with medical comorbidities; DPC, depression with psychiatric comorbidities; MDD, major depressive disorder; tACS, transcranial alternating current stimulation; tDCS, transcranial direct current stimulation; tRNS, transcranial random noise stimulation.
See this image and copyright information in PMC

References

    1. Substance Use and Mental Health Services Administration. National Survey on Drug Use and Health. Published 2023. Accessed May 13, 2025. https://www.samhsa.gov/data/data-we-collect/nsduh-national-survey-drug-u...
    1. Lee SH, Kim YK. Application of transcranial direct and alternating current stimulation (tDCS and tACS) on major depressive disorder. Adv Exp Med Biol. 2024;1456:129-143. doi: 10.1007/978-981-97-4402-2_7 - DOI - PubMed
    1. Yang C, Jung B, Lee SH. Transcranial electrical stimulation: clinical implication and practice for treatment of psychiatric illness. Clin Psychopharmacol Neurosci. 2024;22(3):391-404. doi: 10.9758/cpn.23.1118 - DOI - PMC - PubMed
    1. Zhang R, Lam CLM, Peng X, et al. Efficacy and acceptability of transcranial direct current stimulation for treating depression: a meta-analysis of randomized controlled trials. Neurosci Biobehav Rev. 2021;126:481-490. doi: 10.1016/j.neubiorev.2021.03.026 - DOI - PubMed
    1. Wang J, Luo H, Schülke R, Geng X, Sahakian BJ, Wang S. Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis. BMC Med. 2021;19(1):319. doi: 10.1186/s12916-021-02181-4 - DOI - PMC - PubMed

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