Diagnostic algorithm for clozapine-induced myocarditis: A systematic review.

Clozapine, the gold standard for resistant schizophrenia, is underused due to risks like clozapine-induced myocarditis (CIM). Non-specific biomarkers and inconsistent imaging, and the significant overlap with clozapine-induced pneumonia (CIP) lead to misdiagnosis and premature discontinuation. To develop a diagnostic algorithm for CIM to enhance accuracy, differentiate from CIP, and guide safe clozapine rechallenge. A systematic review of 119 PubMed studies (published between 1990 and April 2025) was conducted in accordance with PRISMA guidelines. The review analyzed CIM diagnosis and rechallenge outcomes, with a focus on biomarkers, imaging, and collaboration with cardiology. CIM diagnosis relies on troponin and C-reactive protein; electrocardiography and echocardiography are inconsistently applied, and cardiac magnetic resonance imaging (CMR) is underused. Rechallenge was successful in 64.7% to 68.9% of 136 cases, with 2.9% resulting in fatal outcomes. Up to 65% of presumed CIM cases lack confirmation. A proposed protocol integrates chest computed tomography to exclude pneumonia and CMR for CIM confirmation, with echocardiography as an alternative. A protocol involving multidisciplinary collaboration among computed tomography, CMR, and cardiology improves CIM diagnosis. Slow titration prevents CIM; adjust the dose for CIP and discontinue for confirmed CIM.