Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial...

Schizophrenia is one of the most severe and costly mental disorders in terms of human suffering and societal expenditure. About 15-30% of patients do not respond to all known antipsychotics, including clozapine, the current gold standard in these cases. Electroconvulsive therapy (ECT) is well-known to be highly effective in clozapine-treatment-resistant schizophrenia (CRS), and synergistic effects of clozapine and ECT have been demonstrated. However, relapse rates after successful courses of ECT are still very high, and evidence for maintenance ECT (mECT) in CRS is scarce at best.

Here, we present the protocol of the MECT-RESIST trial, a German multi-center, observer-blind, randomized, and actively controlled parallel-group clinical trial. The scientific aim of the study is to test the hypothesis that mECT plus treatment as usual (TAU) (intervention group) is superior to TAU alone (control group) for relapse prevention in CRS. The primary endpoint is time to relapse. Secondary endpoints include the proportion of relapse-free patients, the global level of functioning and quality of life, depressive symptoms, overall symptoms of schizophrenia, concomitant catatonic symptoms, stress and self-stigmatization and cognitive performance. We aim at randomizing 84 patients between 18 and 65 years with a clinically diagnosed CRS and brief psychotic rating scale (BPRS) > 45, who responded to a series of ECT (BPRS < 70% of initial BPRS), to either recieve mECT + TAU or TAU over a period of 28 weeks followed by a follow-up of 12 months. The study will be performed between 2025 and 2028.

In this multi-center trial, we aim to examine the effectiveness of mECT in CRS patients who improved after a course of routine ECT. If mECT will lead to a longer time to relapse and/or to a higher proportion of relapse-free patients compared to those undergoing treatment as usual, this trial would have an enormous impact on therapeutic strategies for patients with CRS and would induce a profound change of current treatment guidelines, where ECT still ranks at the level of ultima ratio, despite accumulating evidence suggesting otherwise.

ClincalTrials.gov NCT06456983, registered 7 Jun 2024. Deutsches Register Klinischer Studien DRKS00036886, registered 14 May 2025.