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.