DOI: 10.1001/jamanetworkopen.2026.39400 ISSN: 2574-3805

Home Transcranial Direct Current Stimulation With Gamified Cognitive Control Training for Depression

Esther Dechantsreiter, Frank Padberg, Yuval Benjamini, Stephan Goerigk, Linda Rubene-Kesele, Liene Konosonoka, Ulrike Vogelmann, Tamar Cohen, Naamah Lerner, Gerrit Burkhardt, Aldo Soldini, Fabienne Windel, Marios Fanourakis, Zeno Menestrina, Arthur Nguyen, Angela Pasqualotto, Takuya Morishita, Amir Dotan, Shira Ahissar, Alon Morash, Jonas Björklund, Lucia Bulubas, Daniel Keeser, Netta Assa, Rémy Gardier, Roser Viñals, Jean-Philippe Thiran, Ronen Segman, Omer Bonne, Amit Lotan, Friedhelm C. Hummel, Elmars Rancans, Daphne Bavelier, Mor Nahum

Importance

Transcranial direct current stimulation (tDCS) has emerged as a home-based treatment in major depressive disorder (MDD), although its effects are typically small to moderate and inconsistently observed. Because tDCS may act synergistically with behavioral interventions, combining both approaches represents a promising strategy for developing more effective home-based treatments for MDD.

Objective

To investigate the feasibility, safety, and efficacy of home-based tDCS and concurrent gamified cognitive control training (CCT) in adults with MDD.

Design, Setting, and Participants

This multicenter, double-masked, parallel-group, randomized clinical trial with follow-up at week 10, masking checks at 2 time points, and expectancy assessments was conducted at 3 university hospitals in Latvia, Germany, and Israel between June 22, 2021, and August 8, 2024. Participants included adults aged 18 to 65 years with MDD, 17-item Hamilton Depression Rating Scale scores of at least 13, and no or stable antidepressant medication.

Intervention

Participants were randomly assigned 1:1 to active tDCS (2 mA; anode F3, cathode F4) plus a gamified CCT or sham tDCS plus a sham game. Participants were asked to complete 30 home treatment sessions (30 minutes each) over 6 weeks with software-assisted electrode positioning.

Main Outcomes and Measures

The primary outcome was feasibility, defined as completing at least 20 of 30 sessions with greater than 50% probability. The secondary outcome was efficacy, measured as change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to week 6.

Results

Of 111 enrolled participants, 109 were included in the modified intention-to-treat sample (55 in the active group and 54 in the control group; mean [SD] age, 33.1 [10.6] years; 69 female [63.3%]). Feasibility criteria were met, with 86 participants (78.9%) completing at least 20 sessions (lower bound of 1-sided 95% CI, 71.5%). The MADRS scores improved significantly in both groups at week 6, indicating insufficient evidence to reject the null hypothesis of no difference in the mean change in MADRS score from baseline to 6 weeks between the 2 treatment groups (difference, 0.89 [95% CI, −1.37 to 3.15]; P = .44; Cohen d , 0.10 [95% CI, −0.15 to 0.34]). Results were similar at follow-up (week 10). Adverse events were balanced between groups.

Conclusions and Relevance

This RCT of home-based tDCS combined with CCT in adults with MDD was feasible and safe but did not demonstrate superior efficacy over the control condition. Future studies should refine the mechanistic alignment between stimulation and cognitive interventions to optimize treatment effects.

Trial Registration

ClinicalTrials.gov Identifier: NCT04953208

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