Antipsychotic selection in combination with electroconvulsive therapy for acute schizophrenia: differential efficacy and safety profiles from a real world study

BACKGROUND: Electroconvulsive therapy (ECT) used in combination with antipsychotic medications is an important therapeutic strategy for the management of acute episodes of schizophrenia. However, direct comparisons of the efficacy and safety of different antipsychotic agents when administered alongside ECT remain limited. METHODS: A total of 465 individuals with acute-phase schizophrenia were included in the analysis. All participants underwent six sessions of bitemporal ECT delivered over a two-week period. The primary endpoint was the reduction rate of the Positive and Negative Syndrome Scale total score (PANSS-TRR). Secondary outcomes included reduction rates for the PANSS positive symptom subscale (PANSS-PRR), negative symptom subscale (PANSS-NRR), and general psychopathology subscale (PANSS-GRR). Treatment safety was evaluated using the UKU Side Effect Rating Scale (UKU) and the Gastrointestinal Symptom Rating Scale (GSRS). To reduce subjectivity, we conducted reliability training. RESULTS: Significant symptomatic improvement was observed in all treatment groups following the ECT course. After adjustment for confounding variables, and applying inverse probability of treatment weighting (IPTW) with Bonferroni correction, compared with ECT alone, clozapine-ECT and sulpiride-ECT showed statistically significant advantages in overall symptom reduction (PANSS-TRR). For positive symptom reduction (PANSS-PRR), clozapine-ECT, quetiapine-ECT, risperidone-ECT, and ziprasidone-ECT were associated with significantly greater improvements. No combination demonstrated statistically significant superiority over ECT alone for negative symptoms or general psychopathology after correction. Pairwise comparisons suggested that amisulpride-ECT was associated with smaller improvements in PANSS-TRR compared with clozapine-ECT, risperidone-ECT, and quetiapine-ECT. CONCLUSION: In this observational study of patients with acute phase schizophrenia, the comparative effectiveness and tolerability of antipsychotic medications combined with ECT appeared to differ depending on the specific agent used. These preliminary observations require confirmation in randomized controlled trials before guiding individualized treatment selection. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2500101865. Registered on 30 April 2025. (retrospectively registered). CLINICAL TRIAL NUMBER: ChiCTR2500101865.