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Clozapine-Related Myocarditis and Rechallenge

A Case Series and Clinical Review

Noël, Marie-Christine MD*; Powell, Valerie BScN; Burton, Leah BScN; Panda, Roshni BTech, PhD; Remington, Gary MD, PhD

Journal of Clinical Psychopharmacology: July/August 2019 - Volume 39 - Issue 4 - p 380–385
doi: 10.1097/JCP.0000000000001062
Brief Reports

Purpose/Background That clozapine is the only agent with an indication for treatment-resistant schizophrenia presents real challenges if clozapine-related myocarditis (CIM) occurs. Clinicians have chosen to rechallenge with a second trial of clozapine in the face of CIM. However, there is very limited literature of this topic.

Methods/Procedures Three cases who underwent clozapine rechallenge after CIM are reviewed and discussed in the context of existing literature and current recommendations.

Findings/Results We present 3 young male patients with schizophrenia and schizoaffective disorder who developed CIM during a first clozapine trial, stopped treatment, and subsequently underwent a second clozapine trial. In all cases, the rechallenge was discontinued owing to suspected CIM. A review of the literature includes reports of both successful and unsuccessful clozapine rechallenges after CIM and suggests certain risk factors. Clozapine rechallenge after CIM may be undertaken, as now occurs on occasion with agranulocytosis, although rates of success may be lower. Any such undertaking calls for education, careful monitoring, cautious titration, and a multidisciplinary approach. The balance of risk versus benefits must be considered, and strategies may include a drug holiday, more frequent monitoring upon reinitiation, and slower titration.

Implications/Conclusions Pressure to undertake a rechallenge reflects clozapine's unique role in treatment-resistant schizophrenia and absence of other comparable options. However, it is not without risk, and more research is needed to understand those at increased risk, as well as established strategies that diminish this.

From the *Department of Psychiatry, St Mary's Hospital, McGill University;

Schizophrenia Division, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Quebec, Canada.

Received September 30, 2018; accepted after revision April 28, 2019.

Reprints: Marie-Christine Noël, MD, Department of Psychiatry, St Mary's Hospital, McGill University, 3830 Lacombe, office #3223 Montreal, Quebec, Canada H3T 1M5 (e-mail :

Online date: June 13, 2019

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