Differential effects of transcranial direct current stimulation on depression symptom clusters

Depression is a heterogeneous condition. While transcranial direct current stimulation (tDCS) shows promise, its effects remain inconsistent. Understanding factors underlying this variability could help improve outcomes. Therefore, this study aimed to investigate the differential effects of tDCS versus sham across distinct symptom clusters of depression, using an agglomerative hierarchical clustering approach. Data from a previous IPD meta-analysis of randomized controlled trials (RCTs) involving patients with acute depression who received at least five sessions of tDCS were used. Only RCTs that applied the Hamilton Depression Rating Scale (HAM-D) were included. Symptom clusters were identified using hierarchical clustering of baseline HAM-D item-level data. Changes over time were analyzed using linear mixed-effects models. Ten RCTs were included, involving a sample of 886 patients (active tDCS, n = 387; mean age = 43.1 ± 13.0 years; 66.4% female; sham tDCS, n = 344; mean age = 42.0 ± 13.2 years; 66.3% female), with those assigned to other treatment conditions excluded. Hierarchical clustering revealed four distinct symptom clusters: mood, psychosomatic, insomnia, and psychomotor. Compared to sham, tDCS showed significant improvements in the psychosomatic (ES = -0.35, 95% CI [-0.6, 0.1]), insomnia (ES = -0.33, 95% CI [-0.59, -0.08]), and psychomotor clusters (ES = -0.32, 95% CI [-0.57, -0.06]), but not in the mood cluster (ES = -0.24, 95% CI [-0.5, 0.02). Accessory symptoms showed greater improvement with tDCS, which may reflect the stronger placebo responsiveness of core mood symptoms. These findings support symptom-specific approaches to understanding and optimizing tDCS outcomes.