title: Clozapine-induced myocarditis, a widely overlooked adverse reaction.
abstract: OBJECTIVE
  We review the published cases of clozapine-induced myocarditis and describe reasons for the higher incidence in Australia (>1%) than elsewhere (<0.1%).
  
  
  METHODS
  Medline was searched to September 2014 using 'clozapine' as the sole term.
  
  
  RESULTS
  A total of around 250 cases of clozapine-induced myocarditis have been published. Fever among patients commencing clozapine has been reported internationally, and very few of these cases were investigated for myocarditis. The time to onset of fever is consistent with its being part of a prodrome of undiagnosed myocarditis, and the risk factors are similar to those for myocarditis. In more severe cases, clozapine is discontinued, avoiding fatalities which may occur with myocarditis. Furthermore, cases of sudden death and respiratory illness may well have been undiagnosed myocarditis. The diagnosis of myocarditis is confounded by the non-specific nature of the signs and symptoms, and it depends on appropriate investigations being conducted at the time of myocardial involvement or, for fatal cases, the affected area of the myocardium being sampled for histology.
  
  
  CONCLUSIONS
  It is likely that the incidence of myocarditis is around 3%. Implementation of monitoring procedures will increase case ascertainment and result in more patients benefiting from this valuable medication.
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors: K J
authors: KJ
authors: Ronaldson
authors: Monash Alfred Psychiatry Research Centre, Monash University Central Clinical School and The Alfred Hospital, Melbourne, VIC, Australia.
authors: P B
authors: PB
authors: Fitzgerald
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors: J J
authors: JJ
authors: McNeil
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001315:Australia / Q000453:epidemiology; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000139:chemically induced* / Q000175:diagnosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: clozapine; drug-related side-effects and adverse reactions; incidence; myocarditis