title: A systematic review of clozapine induced cardiomyopathy.
abstract: BACKGROUND
  Clozapine is a unique anti-psychotic medication that is most effective in the treatment of refractory schizophrenia and reducing suicidality. Cardiomyopathy is among the side effects of this medication that limits its use. There are a number of case reports, case series and expert opinion papers discussing clozapine induced cardiomyopathy, but there is no evidence-based review of the subject to guide clinicians.
  
  
  METHODS
  We undertook a systematic review of the literature on cardiomyopathy associated with clozapine. The primary systemic search was in MEDLINE but EMBASE, PsycINFO, and Cochrane were searched and manufacturers of clozapine were contacted for cases. Articles were then individually reviewed to find additional reports.
  
  
  RESULTS
  We identified 17 articles detailing 26 individual cases and 11 additional articles without individual case data. The mean age at time of diagnosis was 33.5 years. The mean dose of clozapine on presentation was 360 mg. Symptoms developed at an average of 14.4 months after initiating clozapine. The clinical presentation was generally consistent with heart failure: including shortness of breath (60%) and palpitations (36%). Echocardiography at presentation showed dilated cardiomyopathy in 39% of cases and was not specified in other cases.
  
  
  CONCLUSIONS
  There should be a low threshold in performing echocardiography in suspected cases of clozapine induced cardiomyopathy. Clozapine should be withheld in the setting of cardiomyopathy without other explanation. There is limited data on the safety of drug re-challenge in clozapine induced cardiomyopathy. Re-challenge may be considered in carefully selected cases but close monitoring and frequent echocardiography are required.
authors.affiliation: Department of Cardiology, Auckland District Health Board, Auckland, New Zealand. Electronic address: alawami241@gmail.com.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alawami
authors.affiliation: Department of Cardiology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Cara
authors.initials: C
authors.lastname: Wasywich
authors.affiliation: Department of Cardiology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Cicovic
authors.affiliation: Department of Liaison Psychiatry, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kenedi
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000401:mortality; D003024:Clozapine / Q000009:adverse effects*; D006801:Humans; D014463:Ultrasonography
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Cardiomyopathy; Clozapine; Echocardiography; Systematic review