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). Results: Significant symptomatic improvement was observed in all treatment groups following the ECT course. After adjustment for confounding variables, the specific antipsychotic agent agent significantly influenced outcomes across all PANSS reduction measures (all p<0.001).Relative to ECT alone, most antipsychotic-ECT combinations demonstrated greater efficacy in reducing overall and positive symptom severity. The combinations of clozapine-ECT, quetiapine-ECT, and ziprasidone-ECT showed the largest adjusted mean differences in PANSS-TRR (MD >43, p<0.05). In contrast, amisulpride-ECT and olanzapine-ECT did not show significant superiority over ECT monotherapy in total symptom reduction (p>0.05). Pairwise comparisons further indicated that amisulpride-ECT was associated with smaller improvements in PANSS-TRR compared with clozapine-ECT, risperidone-ECT, and quetiapine-ECT. Conclusion: Among patients with acute-phase schizophrenia, both the therapeutic effectiveness and tolerability of antipsychotic medications combined with ECT differed depending on the specific agent used. These results may inform individualized treatment selection; however, randomized controlled trials are required to further validate these observations. Trial registration : Chinese Clinical Trial Registry: ChiCTR2500101865. Registered on 30 April 2025. (retrospectively registered).