When, Why and How to Re-challenge Clozapine following Myocarditis

Clozapine-induced myocarditis (CIM) is among the most important side-effects limiting the use of clozapine as the most effective treatment for schizophrenia and schizoaffective disorder. CIM necessitates immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patient’s psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM has been discussed, with published reports indicating a success rate of approximately 60 %. However, compared to re-challenges after clozapine-induced neutropenia for CIM cases remain considerably more limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis, and clinical management of CIM. Moreover, we review current recommendations for re-challenging patients after CIM. We illustrate these issues using a case presentation with a special focus on the relevance of CRP, troponin, NT-proBNP, therapeutic drug-monitoring and cardiac MRI. Our review and case presentation underscore the importance of swiftly attempting to reinitiate clozapine after CIM given the lack of effective alternatives. Cardiac MRI might aid this strategy due to its high sensitivity for detecting myocardial inflammation. Moreover, both previous findings and our case indicate that using slow dose titration regimes and addressing other risk factors for CIM including concomitant valproate are crucial to ensure a safe and successful re-challenge.