Low intensity transcranial electrical stimulation for schizophrenia: a triple-blind, randomized, sham-controlled multicenter trial (STIM’Zo)

Abstract

Persistent symptoms in schizophrenia remain a major therapeutic challenge. Noninvasive electrical stimulation such as transcranial random noise stimulation (tRNS) may alleviate auditory hallucinations and negative symptoms, although existing evidence is limited to case reports and pilot studies. In a triple blind sham-controlled study, we aimed to assess the safety and clinical efficacy of tRNS as an add-on treatment for persistent symptoms in schizophrenia.The primary outcome was clinical response at Day 5, defined as ≥ 25% reduction in PANSS total score. Secondary outcomes included symptom assessments at 1, 3, and 6 months. The primary analysis was performed in 132 patients (64 in the active group: 21 females/43 males; 68 in the sham group: 22 females/46 males). At Day 5, clinical response occurred in 6/64 (9.4%) patients in the active group and 9/68 (13.2%) in the sham group, with no significant difference between groups (-0.38, 95% CI [-1.64, 0.89], p = 0.56). No significant differences were found for secondary outcomes. Serious adverse events unrelated to treatment occurred in 5 (active) vs 7 (sham) patients (0.74, 95% CI [0.17, 2.88], p = 0.76). tRNS was safe and well tolerated but did not show superiority over sham in reducing persistent symptoms of schizophrenia. Trials.gov NCT02744989.