Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia

Abstract Background 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...

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Main Authors: Anton Deicher, Sebastian Karl, Marie-Luise Otte, Johannes Knabbe, Bernadette Wendel, Maria Gose, R. Christian Wolf, Alexander Sartorius
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-06990-2
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author Anton Deicher
Sebastian Karl
Marie-Luise Otte
Johannes Knabbe
Bernadette Wendel
Maria Gose
R. Christian Wolf
Alexander Sartorius
author_facet Anton Deicher
Sebastian Karl
Marie-Luise Otte
Johannes Knabbe
Bernadette Wendel
Maria Gose
R. Christian Wolf
Alexander Sartorius
author_sort Anton Deicher
collection DOAJ
description Abstract Background 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. Methods 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. Discussion 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. Trial registration ClincalTrials.gov NCT06456983, registered 7 Jun 2024. Deutsches Register Klinischer Studien DRKS00036886, registered 14 May 2025.
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spelling doaj-art-cc71ef4f201e4143af62481a617a2d742025-08-20T02:03:32ZengBMCBMC Psychiatry1471-244X2025-05-012511710.1186/s12888-025-06990-2Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophreniaAnton Deicher0Sebastian Karl1Marie-Luise Otte2Johannes Knabbe3Bernadette Wendel4Maria Gose5R. Christian Wolf6Alexander Sartorius7Department of Psychiatry and Psychotherapy, Research Group Brain Stimulation, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Psychiatry and Psychotherapy, Research Group Brain Stimulation, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University HospitalDepartment of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University HospitalCoordination Centre for Clinical Trials (KKS) HeidelbergCoordination Centre for Clinical Trials (KKS) HeidelbergDepartment of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University HospitalDepartment of Psychiatry and Psychotherapy, Research Group Brain Stimulation, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityAbstract Background 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. Methods 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. Discussion 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. Trial registration ClincalTrials.gov NCT06456983, registered 7 Jun 2024. Deutsches Register Klinischer Studien DRKS00036886, registered 14 May 2025.https://doi.org/10.1186/s12888-025-06990-2Electroconvulsive therapyECTMaintenance electroconvulsive therapymECTClozapine-resistant schizophreniaCRS
spellingShingle Anton Deicher
Sebastian Karl
Marie-Luise Otte
Johannes Knabbe
Bernadette Wendel
Maria Gose
R. Christian Wolf
Alexander Sartorius
Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
BMC Psychiatry
Electroconvulsive therapy
ECT
Maintenance electroconvulsive therapy
mECT
Clozapine-resistant schizophrenia
CRS
title Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
title_full Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
title_fullStr Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
title_full_unstemmed Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
title_short Study protocol of a German multi-center, observer-blind, randomized, and actively controlled parallel-group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
title_sort study protocol of a german multi center observer blind randomized and actively controlled parallel group trial comparing maintenance electroconvulsive therapy to treatment as usual for relapse prevention in clozapine resistant schizophrenia
topic Electroconvulsive therapy
ECT
Maintenance electroconvulsive therapy
mECT
Clozapine-resistant schizophrenia
CRS
url https://doi.org/10.1186/s12888-025-06990-2
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