The aim of this study is to evaluate the feasibility and efficacy of transcranial alternating current stimulation (tACS) as an add-on treatment for auditory hallucinations in refractory schizophrenia. Meanwhile, we aim to evaluate the effect of tACS on cognitive function of schizophrenia patients. we hypothesize tACS would improve refractory auditory hallucination symptoms in schizophrenia by regulating the gamma frequency band of temporal lobe。

This is a randomized, double-blind, sham-controlled study to detect the effect of tACS for treatment of refractory auditory hallucinations in schizophrenia. 50 participants were randomly assigned 1:1 to tACS group or sham-control group. For both active and sham group, daily tACS sessions were scheduled in a 5-day sequence for four consecutive weeks, and each session lasted 20minutes. Based on the original and stable medication, active participants were administered 2 mA alternating current delivered with gamma frequency, delivered over the temporal lobe, while controls received sham stimulations with the same protocol. Scale assessments are performed at baseline, week 2, week 4 and week 6. Collection of blood took place at baseline, week 4 and week 6.

Inclusion Criteria:

1. Eligible participants aged 18-70 with DSM-5-defined schizophrenia or schizophrenia-like disorder.
2. Duration of illness > 12 weeks.
3. Being clinically stable and on an adequate therapeutic dose of antipsychotics for at least 8 weeks prior to enrolment.
4. Junior high school education or above
5. After treatment with ≥ 2 different antipsychotics (greater than the equivalent dose of chlorpromazine 600mg), the curative effect was poor (CGI ≥ 4 points or the PANSS score reduction rate since this treatment was less than 20%)
6. Agreement to participate in the study and provide the written informed consent.

Exclusion Criteria:

1. Having unstable medical conditions, current psychiatric comorbidity or active substance use disorder (in exception to caffeine and/or tobacco)
2. Having Serious physical diseases or nervous system diseases;
3. Having any brain device / implant, including cochlear implant and aneurysm clip;
4. Having a history or family history of autoimmune diseases or immune diseases;
5. Pregnancy or breastfeeding at enrollment;
6. Skin lesions on scalp at the area of electrode application.