Fronto-temporal transcranial direct current stimulation reduces symptoms in treatment-resistant schizophrenia: a randomized sham-controlled trial

Treatment-resistant schizophrenia (TRS) remains a major clinical challenge, with limited response to pharmacotherapy. Transcranial direct current stimulation (tDCS) has emerged as a potential adjunctive treatment, although evidence regarding its efficacy remains inconsistent. To evaluate the short-term effects of fronto-temporal tDCS on symptom severity and quality of life in patients with TRS. In this randomized, double-blind, sham-controlled trial, 45 inpatients with TRS were randomized to active or sham tDCS, of whom 39 completed the study (active, n = 20; sham, n = 19). Active tDCS was delivered twice-daily for five consecutive days, whereas sham stimulation consisted of a 30-s ramp-up and ramp-down period, with the current off for the remaining 19 min. Outcomes included the Positive and Negative Syndrome Scale (PANSS) and the WHO Quality of Life-Brief. Intervention effects were assessed using linear mixed-effects models, with ANCOVA as a sensitivity analysis. Active tDCS produced significantly greater reductions in PANSS total and domain scores than sham stimulation ( p < 0.001). Improvements were also observed in quality-of-life outcomes, although these did not remain statistically significant. Fronto-temporal tDCS was associated with short-term symptom improvement in TRS. Larger trials with follow-up are needed to confirm these findings.