Efficacy of transcranial direct current stimulation for depression: individual patient data meta-analysis.

Abstract

Transcranial direct current stimulation (tDCS) shows promise for treating depression, but heterogeneous findings from randomised controlled trials (RCTs) - likely due to patient characteristics and methodological differences - limit clear conclusions about its efficacy. This individual patient data meta-analysis (IPD-MA) aims to evaluate the efficacy of tDCS for depression and explore moderators of clinical depression improvement. Databases (PubMed, Embase, Web of Science, Cochrane Library) were searched up to 1 February 2025 for RCTs comparing active versus sham tDCS in acute depressive episodes. The outcomes were Hedges' g for continuous measures of depressive symptoms, odds ratio for response and remission rates and analyses of individual/methodological moderators of clinical improvement. Acceptability was assessed via dropout rates. Heterogeneity was quantified using the <i>I</i>² statistic. Publication and risk of bias were evaluated with Egger's test and Cochrane Risk of Bias Tool, respectively. Of 29 eligible RCTs, 18 data-sets provided IPD, totalling 1246 included in the IPD-MA (651 active, 595 sham; mean age 43.2, 63.4% female). Most studies (90%) had low risk of bias. Active tDCS showed small but statistically significant effects on depression improvement (Hedges' d = 0.24, 95% CI = 0.11-0.35) and response rates (odds ratio 1.33, 95% CI = 1.04-1.72), with low-to-moderate heterogeneity. No significant difference in remission rates (odds ratio 1.30, 95% CI = 0.98-1.74) and dropout rates (12.7% active, 11.3% sham) were observed between groups. Only sample size significantly moderated clinical improvement, with larger trials showing smaller between-group differences. In this IPD data-set, tDCS showed modest efficacy for depression. Future research should clarify its mechanisms, considering non-specific placebo effects.