Effect of transcranial alternating current stimulation on auditory verbal hallucinations in patients with...

Previous studies have demonstrated the potential of transcranial alternating current stimulation (tACS) to modulate auditory verbal hallucinations (AVH) in patients with schizophrenia (SZ) by regulating neural oscillations. However, the therapeutic efficacy of tACS for treatment-refractory AVH (TRAVH) remains elusive. This study aimed to investigate the efficacy and safety of adjunctive tACS to stable antipsychotic medication for TRAVH in patients with SZ.

A 6-week, randomized (1:1), double-blind, sham-controlled clinical trial was conducted, consisting of a 4-week tACS add-on treatment phase and a 2-week follow-up phase. All participants met the diagnostic criteria for treatment-resistant schizophrenia (TRS) with moderate AVH and were randomly assigned to either the active 40 Hz tACS group or the sham tACS group. The study employed tACS with the left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal junction (TPJ) serving as stimulation electrodes and the Cz as the return electrode. Each session lasted 20 min, administered once daily, five days a week, for a total of four weeks. The primary outcome was the change in scores on the Auditory Hallucination subscale of the Psychotic Symptom Rating Scale (PSYRATS-AH). Repeated-measures analysis of variance (RM-ANOVA) and analysis of covariance (ANCOVA) were used to assess the therapeutic effect of tACS on AVH.

A total of 92 patients were screened, and 39 participants (active group: n = 20; sham group: n = 19) completed the 6-week study. RM-ANOVA revealed a significant time × group interaction for PSYRATS-AH scores at week 6 (P = 0.033) between the two groups, a finding further validated by ANCOVA (P = 0.044). In the active tACS group, improvements in PSYRATS-AH scores at week 2 significantly predicted improvements at week 6 (P = 0.032). No serious adverse events (SAEs) were reported throughout the 6-week trial.

This study suggests that 40 Hz tACS targeting the left DLPFC and left. TPJ is a potentially effective intervention for ameliorating TRAVH in patients with TRS, with a tentative effect on AVH controllability. Additionally, tACS was well tolerated by all participants.