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. 2025 Mar 1;182(3):276-284.
doi: 10.1176/appi.ajp.20240083. Epub 2025 Jan 29.

Spaced Transcranial Direct Current Stimulation for Major Depression

Maxime Couture  1 , Véronique Desbeaumes Jodoin  1 , Emma Bousseau  1 , Arash Sarshoghi  1 , Michael A Nitsche  1 , Daniel M Blumberger  1 , Chantal Bolduc  1 , Cory R Weissman  1 , Lawrence G Appelbaum  1 , Zafiris J Daskalakis  1 , Mohsen Poorganji  1 , Paul Lespérance  1 , Jean-Philippe Miron  1
Affiliations
Free article

Spaced Transcranial Direct Current Stimulation for Major Depression

Maxime Couture et al. Am J Psychiatry. .
Free article

Abstract

Objective: This study investigated spaced transcranial direct current stimulation for major depressive disorder, focusing on feasibility.

Methods: In a prospective open-label study, 30 participants with major depressive disorder were enrolled to receive a 50-session transcranial direct current stimulation (tDCS) treatment over 2 weeks. The feasibility, safety, tolerability, and preliminary therapeutic effects of this tDCS protocol were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline and 1-week and 4-week follow-ups, as well as with the 6-item HAM-D (HAM-D-6) daily during treatment.

Results: The protocol demonstrated good feasibility, with a retention rate of 93.3% and an adherence rate of 99.7%. There were no serious adverse events. The most common side effect was a mild tingling and itching sensation during stimulation (100%) and temporary skin redness following stimulation (100%). Additionally, 64.3% of participants presented with mild irritative contact dermatitis, which had disappeared by the 1-week follow-up for most participants and completely resolved by the 4-week follow-up for the remaining cases; this was not treatment limiting and did not require specific treatment. HAM-D-17 scores decreased from a mean of 21.3 (SD=3.0) at baseline to 15.3 (SD=6.3) at 1 week and 13.2 (SD=7.1) at 4 weeks. Depressive symptom severity, as measured by the HAM-D-17, showed significant reductions over time, with similar trends observed on the MADRS. HAM-D-6 scores highlighted important differences between response groups, particularly during the later stages of treatment, suggesting a potential for differential response patterns between the 1-week and 4-week follow-ups.

Conclusions: The protocol was feasible, safe, and well-tolerated and led to significant reductions in depressive symptoms. These results will need to be validated in a sham-controlled randomized trial. The inclusion of neurophysiological measures in future trials for purposes of biological target engagement might also contribute to our understanding of underlying mechanisms and biomarker discovery.

Keywords: Major Depressive Disorder; Neurophysiology; Neurostimulation; Transcranial Direct Current Stimulation.

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Conflict of interest statement

Dr. Nitsche has served on scientific advisory boards for Neuroelectrics and Precisis, and he has received travel funds from NeuroDevice. Dr. Blumberger has received research support from Brain Canada, the Canadian Institutes of Health Research, NIMH, and the Temerty Family through the CAMH Foundation and the Campbell Family Research Institute; he has received research support and in-kind equipment support for an investigator-initiated study from BrainsWay, and he was the site principal investigator for three sponsor-initiated studies for BrainsWay; he has received in-kind equipment support from MagVenture for two investigator-initiated studies; he has received medication supplies for an investigator-initiated trial from Indivior; he has served as a scientific adviser for Sooma Medical; and he is co-chair of the Clinical Standards Committee of the Clinical TMS Society (unpaid). Dr. Weissman has served as a consultant for GoodCap Pharmaceuticals, and he has received support from the Brain and Behavior Research Foundation, NIMH, and Wellcome Leap. Dr. Daskalakis has received research and in-kind equipment support for an investigator-initiated study through BrainsWay and MagVenture, and he has served on the scientific advisory board for BrainsWay. The other authors report no financial relationships with commercial interests.