Clozapine-induced myocarditis and patient outcomes after drug rechallenge following myocarditis: A systematic case review.

Clozapine is underutilized due, in part, to concerns about rare but severe adverse drug reactions, including cardiac inflammation and injury (myocarditis). Risk factors for clozapine-induced myocarditis are limited and predictors for the successful rechallenge of clozapine after an episode of myocarditis are even more poorly understood. We conducted a systematic review, in accordance with the PRISMA recommendation, of published case reports to describe demographic and clinical characteristics of patients with clozapine-induced myocarditis and identify potential markers of clozapine rechallenge success. A total of 180 cases from 88 articles were evaluated. Male cases of clozapine-associated myocarditis were more frequently reported than female cases by a ratio of 6:1. Less than half of patients reported the presence of chest pain (35%) or flu-like symptoms (43%) but increases in troponin or C-reactive protein were present in 87% of cases. Clozapine rechallenge was carried out in 34 (2 female) cases, with successful reintroduction in 22 (2 female) cases (64.7%) and one fatality (2.9%). No demographic or clinical markers were significantly associated with rechallenge success after correction for multiple testing. Standardized reporting of clozapine-induced myocarditis cases is needed to facilitate the identification of factors associated with successful rechallenge.