Clozapine-Associated Myocarditis: A Protocol for Monitoring Upon Clozapine Initiation and Recommendations for How to Conduct a Clozapine Rechallenge

Background: Clozapine is the only medication with Food and Drug Administration approval for treatment-resistant schizophrenia. However, it is underutilized in the United States because of several life-threatening adverse effects, including clozapine-associated myocarditis (CAM), and a limited understanding of how to manage these complications. To date, recommendations for rechallenging patients with CAM that incorporate the cardiac literature or cardioprotective medications have not been developed. Findings In this article, we outline a protocol developed with cardiologists and guided by the cardiac literature that provides direction on how to monitor for the initial development of CAM and how to rechallenge patients with CAM. Furthermore, we present 2 successful cases of clozapine rechallenge that were managed using this protocol. Conclusions: In both cases, the patients showed marked improvement in their psychiatric symptoms and functioning, demonstrating the importance of considering rechallenge in patients after CAM.