Therapeutic Improvement in People With Schizophrenia Undergoing tACS/CBTp (Transcranial Alternating Current Stimulation/Cognitive Behavioral Therapy for Psychosis) Associated With Usual Medication Regimen: Protocol for a Pilot, Randomized, Single-Blind Trial.

backgroundTranscranial alternating current stimulation (tACS) applies a low-intensity sinusoidal electrical current through electrodes placed on the scalp to boost the brain's own oscillation by way of entrainment. When a single frequency is applied, this exogenous oscillation synchronizes with the brain's endogenous frequency. Gamma frequency synchrony stands out as a binding mechanism for integrating disparate brain networks, mediating perception, cognition, and memory, typically disturbed in schizophrenia. The treatment of schizophrenia includes medication and cognitive behavioral therapy for psychosis (CBTp). We are adding tACS to these usual treatments, targeting gamma oscillation stimulation, to augment the CBTp efficacy in people living with schizophrenia.

objectiveThis study aims to elicit cognitive readiness and therapeutic engagement by adding tACS to each CBTp session in individuals with schizophrenia taking their usual medication, to evaluate the possible improvement of the level of functioning, and to determine if the response to intervention is gender specific.

methodsThis is a pilot, prospective, randomized, repeated-measures, single-blind study design. We expect to enroll 28 participants randomly assigned to one of two treatment arms: arm 1 (tACS/CBTp, n=14) or arm 2 (sham tACS/CBTp, n=14; tACS is sham, but CBTp is active). The intervention with active or sham tACS/CBTp will take place weekly for 16 weeks. Primary outcome measures-electroencephalogram, Positive and Negative Syndrome Scale, 16-item Negative Symptom Assessment, and Cognitive Flexibility Scale-will evaluate the efficacy of treatment at the end of the intervention and at the two follow-ups. We will use SPSS (version 29, IBM Corp); the main tests will include repeated measures and mixed design ANOVA.

resultsThe timeline for recruitment, treatment, and follow-ups is 18 months, followed by 6 months for data analysis, writing manuscripts, and dissemination activities. By November 1, 2025, we have enrolled 15 participants: 12 are following the intervention protocol (8 active and 4 sham tACS). Two participants were screening failures, and one participant withdrew after intervention 2.

conclusionsOur expectations are as follows. CBTp will improve the scores of psychological and psychosocial tests at the end of therapy for both groups, but it will be superior for the group with tACS intervention. Considering that cognitive and emotional status is gender dependent (hormonal differences, brain structure, and sociocultural influences), we expect that the therapeutic response could be gender specific. CBTp will enhance electroencephalogram activity and the heart in clients with schizophrenia at the end of therapy for both groups, but it will be superior for the group with tACS preintervention. The baseline heart rate variability will predict symptom improvement and will increase over the course of therapy. We hope our research will improve the treatment of people living with schizophrenia, thereby enhancing their quality of life, reducing the rate of relapse, and lowering the costs of care.

trial registrationClinicalTrials.gov NCT06889025; https://clinicaltrials.gov/study/NCT06889025. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/80593.