Optimized multichannel 4 mA vs conventional transcranial direct current stimulation for major depressive disorder: A randomized sham-controlled trial.

Overview

1. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Medical Faculty, RWTH Aachen University,Aachen, Germany
2. Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors,Dortmund, Germany
3. Department of Clinical Psychology, Faculty of Medicine, Zanjan University of Medical Sciences,Zanjan, Iran
4. Donders Institute for Brain, Cognition, and Behaviour, Radboud University,Nijmegen, The Netherlands
5. Department of Information Technology and Electrical Engineering, ETH Zurich,Zurich, Switzerland
6. Department of Biomedical Engineering, Faculty of Electrical Engineering, K. N. Toosi University of Technology,Tehran, Iran
7. Neuroelectrics Barcelona,Barcelona, Spain
8. Bielefeld University, University Hospital OWL, Protestant Hospital of Bethel Foundation, University Clinic of Psychiatry and Psychotherapy,Bielefeld, Germany
9. German Center for Mental Health,Bochum, Germany

Abstract

Major depressive disorder is a prevalent mental condition and the second most disabling disease. Transcranial direct current stimulation (tDCS), with advantages such as affordability, home-use application, and mild side effects, has been proposed for treating depression. Yet, its clinical efficacy is not established. Optimizing tDCS interventions for more effective and feasible clinical application is a need and topic of ongoing research. This randomized, sham‑controlled trial compares the efficacy of computationally optimized multichannel tDCS (4 mA), a less source-demanding alternative for personalized tDCS, vs conventional tDCS (2 mA) for treating unipolar depression. Seventy-one patients were randomly assigned to the optimized multichannel tDCS, conventional tDCS, and sham tDCS arms, of whom 60 provided endpoint data. In the optimized multichannel tDCS, electrical current was delivered via 7 small electrodes (max 1.65 mA per electrode; total injected current per polarity ≈ 4 mA [precisely 3.99 mA]) while in the conventional (2 mA per electrode) and sham tDCS, two 35 cm² sponge electrodes were used. Intervention efficacy and treatment response were evaluated before the intervention, at weeks 2, 4, 6, and 1- and 3-month post-intervention, and cognitive functions and brain connectivity changes were assessed before and after the intervention. Both active tDCS interventions significantly reduced depressive symptoms compared to the sham group after the intervention. The optimized multichannel tDCS demonstrated earlier and stronger symptom alleviation than conventional tDCS. It additionally improved cognitive control and modulated functional connectivity markers associated with depression pathophysiology. The mean change in the primary clinical outcome from baseline to the study endpoint was 6.30 in the sham group and 13.50 and 21.50 in the conventional and multichannel tDCS groups, with corresponding response rate (≥50% symptom reduction) of 20% (4/20), 45% (9/20), and 75% (15/20), respectively. Blinding was unsuccessful only in the optimized multichannel arm, likely due to more intense stimulation-related sensations, however, this did not impact clinical outcomes. The optimized multichannel 4 mA tDCS shows clinical efficacy for treating depression, warranting further investigations in the future. Trial Registration Identifier: NCT06165445 / IRCT20210517051330N1.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• osf:xm4vq, at OSF; found in “Data availability”

Data availability

The data used in this trial will be publicly available at OSF upon manuscript publication via: https://osf.io/xm4vq/overview?view_only=8d2e65ed25ec437c911eaecb8c34ae5d

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

• Publisher: n/a → Springer Nature

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 2 keywords, 9 MeSH terms, 1 funder, 73 references, 1 integrity notice.

Cite

This paper

Salehinejad, M. A., Abdi, M., Dadashi, M., Habibi, M., Hallajian, A.-H., Sharifi, K., Khadem, A., Salvador, R., Ruffini, G., & Nitsche, M. A. (2026). Optimized multichannel 4 mA vs conventional transcranial direct current stimulation for major depressive disorder: A randomized sham-controlled trial. Molecular psychiatry, 31(8), 4632-4644. https://doi.org/10.1038/s41380-026-03560-0

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41380-026-03694-1 [code]

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Journal: Molecular psychiatry

In common: other, clinical / translational, 3 references

[2] doi:10.3389/fnins.2026.1803897 [code]

Multimodal imaging-based targeting approach for network-level brain stimulation.

Journal: Frontiers in neuroscience

In common: other, 3 references

[3] doi:10.1162/imag.a.1222 [code]

Network-based near-scalp personalized brain stimulation targets.

Journal: Imaging neuroscience (Cambridge, Mass.)

In common: other, 3 references

[4] doi:10.3390/s26103065 [code]

Subject-Wise Depression Screening from Eight-Channel Resting-State EEG Using Asymmetry-Aware Spectral Features and Connectivity Ablation.

Journal: Sensors (Basel, Switzerland)

In common: depression, other, 2 references

[5] doi:10.1016/j.neurot.2026.e00884 [code]

Test-retest reliability and symptom association of personalized depression TMS targets: A comparative study of refined seed-based (RSA) and hierarchical clustering (HCA) approaches.

Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

In common: depression, other, clinical / translational, 2 references

[6] doi:10.1038/s43856-026-01595-6 [code]

Non-vectorial integration of intersectional short-pulse stimulation enables enhanced deep brain modulation and effective seizure control.

Journal: Communications medicine

In common: 3 references

[7] doi:10.1111/pcn.70066

Acute prefrontal hemodynamic responses to intermittent theta burst stimulation correlate with current depression and episode recurrence: A cross-sectional study.

Journal: Psychiatry and clinical neurosciences

In common: depression, other, 2 references

[8] doi:10.1007/s12311-026-02037-8

Cerebellar Transcranial Alternating Current Stimulation: Frequency-Specific Modulation of Human Gait.

Journal: Cerebellum (London, England)

In common: other, 2 references

[9] doi:10.1038/s41386-026-02471-6

Investigating the effect of increased dopamine signaling on cerebral blood flow in Major Depressive Disorder: a double-blind randomized placebo-controlled study.

Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

In common: depression, clinical / translational, 2 references

[10] doi:10.1073/pnas.2519586123 [code]

Personalized functional topography-based multisite brain age prediction modeling reveals divergent neurodevelopment in major depression.

Journal: Proceedings of the National Academy of Sciences of the United States of America

In common: depression, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.