A systematic review of transcranial electrical stimulation and meta-analysis of transcranial direct current stimulation RCTs in unipolar and bipolar depression

BACKGROUND: Therapies for major depressive episodes (MDEs) in major depressive disorder (MDD) and bipolar disorder (BD) have limited efficacy and tolerability. Transcranial electrical stimulation (tES), including transcranial direct current (tDCS), alternating current (tACS), and random noise stimulation (tRNS), has been investigated as a non-invasive alternative, but existing reviews are outdated or narrow in scope. METHODS: A systematic review of tES modalities for MDE in MDD and BD was conducted, alongside a meta-analysis restricted to tDCS RCTs. Eligible participants had MDD or BD diagnosed per standardised criteria. The primary outcome was change in depression severity; secondary outcomes were response and remission. Moderator and sensitivity analyses were performed post hoc. RESULTS: Thirty-four tES trials met inclusion criteria; 31 used tDCS (n = 1833 at endpoint) and were eligible for meta-analysis. Pooled results showed active tDCS produced a moderate reduction in depressive symptoms versus sham (Hedges' g = 0.387, 95% CI: 0.192-0.582), with no significant effect on response (OR = 1.397) or remission (OR = 1.138). Larger effects were observed in bipolar depression, monotherapy samples, and studies using F3/F4 electrode placement. No publication bias was detected. Risk of bias ratings influenced effect sizes. DISCUSSION: tDCS demonstrates statistical superiority to sham for symptom reduction, but effects do not reliably translate to response or remission, and heterogeneity remains substantial. Efficacy varies by clinical and methodological factors. CONCLUSION: tDCS is a safe, moderately effective option for MDEs. Future trials should improve methodological rigor, refine montage selection, and evaluate longer or multi-channel protocols.