Sequential Treatment Approaches for Treatment-Resistant Schizophrenia

This is a sequential, assessor-blinded randomized controlled trial in Chinese patients with treatment-resistant schizophrenia (TRS). The study consists of two treatment components. First, clozapine-naive TRS participants will enter an 8-week pharmacological optimization phase and be assigned to one of three treatment groups: clozapine monotherapy, clozapine plus amisulpride, or clozapine plus aripiprazole. Second, eligible participants will enter a 4-week assessor-blinded neuromodulation phase comparing modified electroconvulsive therapy (MECT) and magnetic seizure therapy (MST). Participants for this phase are either (1) patients who have previously received clozapine and are hospitalized due to symptom exacerbation, or (2) participants who completed the pharmacological optimization phase and showed inadequate response, defined as less than 25% reduction in PANSS total score at Week 8. The study is expected to provide evidence on the effectiveness, cognitive safety, and overall tolerability of these treatments for TRS. The project has important clinical significance.