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

Molecular Psychiatry, vol. 31, pp. 4632–4644

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.

Authors 10

1. Mohammad Ali Salehinejad corresponding Aachen Medical Faculty Department of Child and Adolescent Psychiatry

   RWTH Aachen University · Leibniz Research Centre for Working Environment and Human Factors

   Affiliation as printed

   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Medical Faculty, RWTH Aachen University, Aachen, Germany. msalehinejad@ukaachen.de

   Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany. msalehinejad@ukaachen.de

2. Marzieh Abdi

   Zanjan University of Medical Sciences

   Affiliation as printed

   Department of Clinical Psychology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

3. Mohsen Dadashi

   Zanjan University of Medical Sciences

   Affiliation as printed

   Department of Clinical Psychology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran. Mohsendadashi@zums.ac.ir

4. Maryam Habibi

   Zanjan University of Medical Sciences

   Affiliation as printed

   Department of Clinical Psychology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

5. Amir‐Homayun Hallajian

   Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Nijmegen, The Netherlands

6. Kiomars Sharifi

   ETH Zurich

   Affiliation as printed

   Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland

7. Ali Akbar Khadem

   K. N. Toosi University of Technology

   Affiliation as printed

   Department of Biomedical Engineering, Faculty of Electrical Engineering, K. N. Toosi University of Technology, Tehran, Iran

8. Ricardo Salvador

   Neuroelectrics Barcelona SLU (Spain)

   Affiliation as printed

   Neuroelectrics Barcelona, Barcelona, Spain

9. Giulio Ruffini

   Neuroelectrics Barcelona SLU (Spain)

   Affiliation as printed

   Neuroelectrics Barcelona, Barcelona, Spain

10. Michael Andreas Nitsche

    Bielefeld University · Leibniz Research Centre for Working Environment and Human Factors · Deutsches Zentrum für Psychische Gesundheit

    Affiliation as printed

    Bielefeld University, University Hospital OWL, Protestant Hospital of Bethel Foundation, University Clinic of Psychiatry and Psychotherapy, Bielefeld, Germany

    Department of Psychology and Neurosciences, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany

    German Center for Mental Health, Bochum, Germany