Cognitive effects of transcranial random noise stimulation in schizophrenia: A triple-blind randomized placebo-controlled pilot study

Transcranial random noise stimulation (tRNS) has shown promising effects on working memory, attention, and learning in healthy individuals and other clinical populations. However, evidence for cognitive benefits in schizophrenia remains limited, despite the high prevalence and clinical relevance of cognitive impairments in this group. This triple-blind, randomized, placebo-controlled pilot study (DRKS00005200) investigated the effects of tRNS on cognitive and clinical outcomes in 30 individuals with schizophrenia. Patients received either active or sham tRNS, with the anodal electrode placed over the left dorsolateral prefrontal cortex (F3 according to the international 10-20 EEG system). Stimulation consisted of a high-frequency current oscillating between 1 mA and 2 mA, applied for 20 min daily over two weeks, alongside stable antipsychotic treatment. Across primary outcomes (cognition and psychopathology), no clear evidence for robust between-group differences was observed. Effect sizes were consistently small with overlapping confidence intervals. Both groups showed comparable improvements in working memory (n-back), verbal learning (VLMT-A), attention (d2), and clinical symptoms over time. Secondary analyses indicated a small-to-moderate effect in attentional processing speed, although estimates were imprecise. Exploratory analyses further suggested a potential moderation effect in SANS anhedonia, indicating differential associations between baseline severity and follow-up outcomes across groups. Overall, the pattern of findings does not provide evidence for specific cognitive or clinical benefits of tRNS in this sample. Observed within-group improvements may reflect non-specific effects such as practice-related gains and study participation, although these cannot be isolated within the present design. Future studies should address inter-individual variability by targeting specific cognitive domains and symptom clusters, incorporating longer follow-ups, more sensitive and parallelized assessments, and optimized stimulation protocols, potentially combined with cognitive training, to clarify conditions under which tRNS may yield clinically meaningful effects in schizophrenia.