Clozapine-induced myocarditis in children and adolescents: a pharmacovigilance study using VigiBase and a systematic literature review

Carlos De Las Cuevas, Manuel Arrojo-Romero, Can Jun Ruan, Georgios Schoretsanitis, Emilio J. Sanz, Jose de Leon

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


Introduction: Clozapine-induced myocarditis in children (age ≤18 yo) was studied from a PubMed search (18 July 2022) (9 cases) and from the World Health Organization’s pharmacovigilance database, called Vigibase, of adverse drug reaction (ADR) reports (72 non-duplicated cases). VigiBase uses a logarithmic measure of disproportionality called the information component (IC). A logistic regression model of presence/absence (40/32) of seriousness in VigiBase was developed. Areas covered: VigiBase provided a significant myocarditis IC = 4.2 with an IC025 = 3.8; only 4 clozapine-induced myocarditis cases were expected, while 72 were observed. The PubMed search identified 9 cases, while VigiBase identified 72 cases (of which 67 did not overlap with published cases). These 76 combined cases included 35 doubtful (most with missing information on the day of diagnosis), 19 possible and 22 probable, according to the ADR scale. After adjusting for confounders, quetiapine increased the risk of seriousness with an odds ratio (OR) of 17.6 (95% confidence interval CI, 1.56 to 198.6), while Australian origin decreased it with an OR = 0.13 (CI, 0.04 to 0.47). Expert opinion: These 41 cases of at least possible clozapine-induced myocarditis indicated that this ADR can definitively occur in children, particularly in the first 30 days of up-titration. Children’s and adult cases appeared similar.

Original languageEnglish
Pages (from-to)715-727
Number of pages13
JournalExpert Opinion on Drug Metabolism and Toxicology
Issue number11
StatePublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.


  • Adolescent
  • clozapine/adverse effects
  • clozapine/metabolism
  • clozapine/toxicity
  • mortality/drug effects
  • myocarditis/chemically induced
  • myocarditis/etiology

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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