Transcranial Direct Current Stimulation (tDCS) in the Treatment of Youth Depression: Integrating Literature Review Insights in a Pilot Clinical Trial

<b>Background</b>: Youth (ages 16-25) is a key window for mental health interventions, as depression rates significantly increase during this developmental stage. However, transcranial direct current stimulation (tDCS) application in youth depression remains underexplored. To reduce the uncertainty of a future trial, we conducted a review and a pilot randomised controlled trial (RCT) of tDCS for youth depression. <b>Methods</b>: Following the PRISMA guidelines, the first part of this study was a review across databases including PubMed, MEDLINE, PsychInfo, CINAHL, Open Access Theses and Dissertations (OATD), WanFang Data, Chinese Medical Journal, and clinical trial registries up to 20 November 2024, on tDCS treatment for youth depression. The second part of this study was a double-blind pilot RCT assessing feasibility, by comparing active tDCS (five daily 30 min 2 mA anodal tDCS applications over the left dorsolateral-pre-frontal-cortex (DLPFC) with sham tDCS. Feasibility outcomes included recruitment, data collection, attendance, retention and randomisation. Outcomes also included depression severity using the Hamilton Depression Rating Scale (HDRS), safety, tolerability, acceptability, and adequacy of blinding. Mann-Whitney U tests were used for between-group comparison. <b>Results</b>: Fourteen eligible studies were identified, with a pooled HDRS reduction of -9.6 (95% CI: -11.2 to -8.1, <i>p</i> < 0.001), though high risks of bias indicated a research gap. Using parameters derived from the review, we conducted a pilot RCT in which 20 youths were screened and 8 were randomised (aged 16-24; 3 females, 5 males). All randomised participants completed their assigned sessions without dropout or protocol discontinuations. Blinding was adequate, and participants' willingness to engage improved over time. Both groups showed reductions in HDRS, with a greater mean reduction in the active group (-4.75 ± 2.96) compared to the sham group (-3.75 ± 3.78). No serious adverse events occurred, with only mild headaches and tingling reported. The tolerability profile was comparable. However, the decentralised administration of sessions may have introduced inconsistent tDCS applications. <b>Conclusions</b>: This review highlights a lack of RCTs on tDCS for youth depression. Our pilot trial demonstrates the feasibility of a sham-controlled design in youth depression, justifying larger-scale trials to evaluate the efficacy of tDCS in this population.