Effectiveness and safety of adjunctive transcranial direct current stimulation for adolescents with first-episode major depressive disorder: A randomized, double-blind, sham-controlled trial

Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation method, can improve depressive symptoms by applying weak electric direct currents to the scalp. This study aimed to evaluate the efficacy and safety of adjunctive tDCS for adolescents with first-episode major depressive disorder (FE-MDD).

This double-blind, randomized, sham-controlled trial (RCT) was conducted between January 3, 2024, and August 24, 2024. Adolescents (aged 13-17 years) with FE-MDD were included and randomly allocated to active tDCS group or sham tDCS group. Patients completed 10 sessions of active tDCS or sham tDCS, 1 session per day on weekdays for 2 weeks. The main outcome was the change score in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the last session of tDCS. Secondary outcomes included response rate, remission rate, and changes in neurocognitive function, with the latter assessed by the MATRICS Consensus Cognitive Battery. Clinical response was defined as a ≥ 50 % reduction in the MADRS score from baseline to the 10th tDCS session. Clinical remission was defined as MADRS scores equal to or less than 10 at the 10th tDCS session.

Twenty patients in the active tDCS group and 20 patients in the sham tDCS group were included in the intention-to-treat analysis. A linear mixed model adjusting for baseline MADRS scores and daily chlorpromazine equivalents revealed no significant interactions between time and tDCS condition in MADRS scores (F_3,114 = 0.65; p = 0.59). Rates of response (14 of 20 patients [70 %; 95 % CI, 50 %-90 %] versus 9 of 20 patients [45 %; 95 % CI, 25 %-65 %]; χ² = 2.56; p = 0.11) and remission (11 of 20 participants in the active tDCS group [55 %; 95 % CI, 35 %-75 %] versus 10 of 20 participants in the sham tDCS group [50 %, 95 % CI, 30 %-70 %]; χ² = 0.10; p = 0.75) were higher in the active tDCS group than in the sham tDCS group, though these group differences were not statistically significant. However, statistically significant group by time interactions were observed in cognitive domains of working memory (F_1,38 = 4.14; p = 0.049) as well as verbal learning and memory (F_1,38 = 8.22; p = 0.01). No serious adverse effects were observed in either group. The active tDCS group (versus the sham tDCS group) had a significantly higher incidence of post-tDCS headaches (85 % [95 % CI, 65 %-100 %] versus 50 % [95 % CI, 30 %-70 %]; χ² = 5.58; p = 0.02), but the incidence of other side effects (e.g., dizziness, diarrhea) did not differ significantly between the two study groups.

Findings of this RCT suggest that active tDCS is safe for adolescents with FE-MDD. Although no statistically significant difference between groups over time was observed in the primary efficacy outcome, patients in the active tDCS group did have a greater proportion of remission and response. Furthermore, active tDCS was associated with comparatively stronger improvements in working memory as well as verbal learning and memory when compared to sham tDCS.