Clozapine-induced myocarditis and subsequent rechallenge: a narrative literature review and case report

Clozapine is an antipsychotic medication that has been proven effective for the management of treatment-resistant schizophrenia (TRS). For some patients, it is the only medication that can improve disease burden and quality of life. Clozapine comes with various potentially serious adverse effects which may dissuade physicians from prescribing it despite its well-documented efficacy. One of these adverse effects is clozapine-induced myocarditis (CIM). Due to these risks, patients who undergo a clozapine rechallenge after CIM require close monitoring. Myocardial damage can be reversible if CIM is promptly identified, and clozapine is discontinued appropriately. The gold-standard for diagnosing myocarditis is an endomyocardial biopsy but there are no clear recommendations for how to use less invasive screening assessments to monitor for CIM during a clozapine rechallenge. This review article aims to increase awareness of CIM and provide guidance on monitoring and management. The accompanying case report presents a proposed strategy, including biomarkers that were used to identify inflammation and cardiac injury which guided the treatment of an adolescent patient who had a successful clozapine rechallenge. Further research is necessary to validate the proposed monitoring protocol and to further advance guidance for clinicians.