Long-term trajectories of treatment-resistant schizophrenia following clozapine or electroconvulsive therapy: A retrospective observational study.

BACKGROUND

Clozapine (CLZ) is the first-line treatment for treatment-resistant schizophrenia (TRS), but practical constraints often delay its implementation. Approximately 50 % of patients ultimately discontinue CLZ, primarily due to adverse events. Electroconvulsive therapy (ECT) has shown efficacy in TRS, though concerns remain regarding the durability of its effects. This study aimed to characterize the treatment effectiveness and clinical trajectories of patients with TRS following initial treatment with CLZ or ECT.

METHODS

This study reviewed medical records of 116 patients with TRS initially treated with either CLZ (n = 63) or ECT (n = 53) at three tertiary care centers in Japan (2000-2020). The primary outcome was time to treatment failure, defined as readmission, ECT initiation, CLZ discontinuation/initiation, interruption of hospital attendance, or all-cause death. We traced patients' trajectories following initial treatment failure.

RESULTS

Both groups showed similar treatment failure rates in the first year. Beyond this period, the CLZ group exhibited diminishing failure rates (median time: 2093 days), with discontinuation as the main reason. Among CLZ responders (42.9 %), 81.5 % maintained stability without readmission. The ECT group showed consistent failure occurrence (median: 589 days), with readmission as the primary reason. Despite low maintenance ECT utilization (13.2 %), approximately 40 % of ECT patients maintained stability over two years.

CONCLUSIONS

Our findings described different long-term trajectories in TRS following CLZ or ECT as initial treatments, highlighting the importance of extended follow-up. Considering long-term stability, timely CLZ initiation is preferable. ECT can be a valuable alternative when CLZ implementation is impractical, providing clinical stability in a substantial proportion of patients.