Real-World Effects of Home-Based Transcranial Direct Current Stimulation in Depression: A Randomized Controlled Trial of 3-Week Versus 6-Week Protocols.

BACKGROUND: Despite growing interest in home-based transcranial direct current stimulation (tDCS) as a scalable treatment for depression, real-world evidence regarding its effectiveness, cognitive impact, and safety remains limited. Moreover, the optimal stimulation duration for home-based tDCS has not been clearly established. This study aimed to compare the clinical effects of two home-based tDCS protocols-one with 3 weeks of active stimulation followed by 3 weeks of sham stimulation (3WA) and another with 6 weeks of active stimulation (6WA)-in patients with major depressive disorder (MDD). METHODS: In this randomized controlled trial, participants diagnosed with MDD were assigned to either the 3WA or 6WA group. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Cognitive function was assessed with the Digit Symbol Substitution Test (DSST). Adverse events were systematically monitored, and the relationship between psychotropic medication use and adverse event frequency was analyzed using logistic regression. RESULTS: Both groups showed significant improvements in depressive symptoms and cognitive performance across four assessment points (baseline, Weeks 3, 6, and 12). Linear mixed-effects models revealed a significant main effect of time for both BDI (F = 33.67, p < 0.001) and MADRS scores (F = 34.50, p < 0.001), with no significant group-by-time interaction, indicating comparable efficacy between protocols. Model-derived mean changes from baseline to Week 12 were -7.53 (95% CI -9.85 to -5.21) for BDI and -6.61 (95% CI -8.73 to -4.49) for MADRS. DSST scores also improved significantly over time (F = 55.8, p < 0.001), with a mean increase of +6.62 points (95% CI +5.17 to +8.05), again showing no significant group difference. Regarding safety, non-medicated participants reported fewer adverse events, whereas those taking tianeptine experienced significantly more side effects compared with other medication groups. CONCLUSIONS: Both 3-week and 6-week active tDCS protocols were associated with improvements in depressive symptoms and cognitive function over time in this naturalistic clinical context; however, as the study did not include a sham control, these changes should be interpreted as comparative rather than causal effects. The 3- and 6-week protocols demonstrated similar therapeutic outcomes, suggesting that shorter courses may be sufficient. These findings support the real-world applicability of at-home tDCS and highlight the need to consider concurrent pharmacotherapy when evaluating tolerability and safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05539131.