205. Usefulness of clozapine as maintenance pharmacotherapy after response to acute electroconvulsive therapy in schizophrenia

Abstract

Abstract Background Treatment-resistant schizophrenia (TRS)—defined as insufficient response to at least two different atypical antipsychotics—affects approximately 20–33% of individuals with schizophrenia and has been linked to dopamine D₂-receptor supersensitivity. Although clozapine is the internationally recommended first-line therapy for TRS, its real-world uptake in Japan remains limited; a 2023 nationwide survey reported that 79.3% of TRS patients who underwent acute electroconvulsive therapy (ECT) had never received clozapine. Acute ECT yields at least moderate response in roughly 63% of TRS cases, yet 1-year relapse remains common (40–60%). Because ECT may mitigate D₂-receptor hypersensitivity, combining an acute ECT response with clozapine maintenance is a biologically plausible strategy to sustain remission. Aims & Objectives To retrospectively evaluate the effectiveness of clozapine as maintenance pharmacotherapy following an acute ECT response in TRS. Method We retrospectively reviewed consecutive TRS patients who responded to an acute ECT course and subsequently initiated clozapine for maintenance during the period from April 1, 2012 to May 31, 2025. Relapse was defined a priori as a Clinical Global Impressions–Improvement (CGI-I) score ≥6 or psychiatric rehospitalization. Paired pre–post comparisons (e.g., Brief Psychiatric Rating Scale scores, chlorpromazine-equivalent dose) used the Wilcoxon signed-rank test. The planned two-site cohort comprises NHO Kure Medical Center & Chugoku Cancer Center (Kure, Japan) and Cocoro Hospital Kusatsu (Hiroshima, Japan). As of abstract submission, only the Kure cohort (n=10) has been fully curated and is reported here. Data from Cocoro Hospital Kusatsu (≈30 cases) are being finalized and will be included in the oral presentation, together with pooled multivariable analyses. The study complied with the principles of the Declaration of Helsinki and was approved by the Ethics Committees of NHO Kure Medical Center and Chugoku Cancer Center and Cocoro Hospital Kusatsu. Results Mean age at ECT was 40.1 ± 16.9 years; patients had experienced 6.8 ± 12.4 prior hospitalizations. Brief Psychiatric Rating Scale scores decreased from 76.0 ± 11.8 pre-ECT to 29.4 ± 4.7 post-ECT (Wilcoxon signed-rank test, p < 0.001). The chlorpromazine-equivalent antipsychotic dose fell from 1356.2 ± 902.4 mg/day before ECT to 605.0 ± 320.3 mg/day at discharge (Wilcoxon signed-rank test, p = 0.037). The 1-year relapse rate estimated by the Kaplan–Meier method was 33.5%, and this rate remained essentially stable over long-term follow-up (up to 10 years). Discussion & Conclusions In this interim single-site analysis, clozapine maintenance after an acute ECT response was associated with a 1-year relapse rate below 40% in TRS, comparing favorably with historical rates of 40–60%. These findings support a pragmatic sequence—rapid stabilization with ECT followed by clozapine—to reduce post-ECT relapse in TRS. At the time of presentation, we will also report results from Cocoro Hospital Kusatsu and present pooled multivariable models (e.g., Cox regression) to identify predictors of relapse prevention across both sites. If confirmed, this approach could inform practice where clozapine uptake remains suboptimal and help address the current gap in guidance on maintenance strategies after ECT.