Clozapine-induced myocarditis in Russia: Animal studies but no clinical studies.

Abstract

In 1980, Vesterby et al.1 published the first case of clozapine-induced myocarditis during an overdose. In 1990, after another case of clozapine-induced myocarditis during an overdose, Meeker et al.3 described a case of eosinophilic myocarditis characterized by an infiltration of eosinophils. Eosinophilic myocarditis is the typical presentation of clozapine-induced myocarditis and is indicative of a drug hypersensitivity reaction.3 During the 1990s, the national drug agencies started paying attention to this clozapine adverse drug reaction (ADR).4 VigiBase, the database of the World Health Organization, receives data from the national drug agencies. In early 2021, a VigiBase search identified more than 3000 cases of clozapineinduced myocarditis associated with a 5% mortality rate (178/3572). Almost all the cases of myocarditis in clozapine patients appeared early in treatment with 84% (1309/1560) in the first month and another 5% (82/1560) in the second month, which is compatible with clozapine uptitration that was too rapid for the metabolism of that specific patient.4 The occasional cases of myocarditis following clozapine overdose have the same mechanism. In the VigiBase search, there were no reports of clozapine-induced myocarditis from the Russian drug agency.