Adverse cardiac events in out-patients initiating clozapine treatment: a nationwide register-based study

Acta Psychiatr Scand. 2018 Jan;137(1):47-53. doi: 10.1111/acps.12827. Epub 2017 Oct 24.


Objective: Using national Danish registers, we estimated rates of clozapine-associated cardiac adverse events. Rates of undiagnosed myocarditis were estimated by exploring causes of death after clozapine initiation.

Method: Through nationwide health registers, we identified all out-patients initiating antipsychotic treatment (January 1, 1996-January 1, 2015). Rates of clozapine-associated myocarditis and pericarditis within 2 months from clozapine initiation and rates of cardiomyopathy within 1-2 years from clozapine initiation were compared to rates for other antipsychotics. Mortality within 2 months from clozapine initiation was extracted.

Results: Three thousand two hundred and sixty-two patients of a total 7932 patients initiated clozapine as out-patients (41.12%). One patient (0.03%) developed myocarditis, and no patients developed pericarditis within 2 months from clozapine initiation. Two (0.06%) and four patients (0.12%) developed cardiomyopathy within 1 and 2 years respectively. Rates were similar for other antipsychotics. Twenty-six patients died within 2 months from clozapine initiation. Pneumonia (23.08%) and stroke (11.54%) were the main causes of death. We estimated the maximum rate of clozapine-associated fatal myocarditis to 0.28%.

Conclusion: Cardiac adverse effects in Danish out-patients initiating clozapine treatment are extremely rare and these rates appear to be comparable to those observed for other antipsychotic drugs.

Keywords: Danish nationwide registers; antipsychotics; cardiomyopathy; clozapine; mortality; myocarditis; pericarditis.

MeSH terms

  • Adult
  • Aged
  • Ambulatory Care
  • Antipsychotic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Cardiomyopathies / epidemiology*
  • Clozapine / therapeutic use*
  • Denmark / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocarditis / epidemiology*
  • Pericarditis / epidemiology*
  • Psychotic Disorders / drug therapy*
  • Registries*
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Clozapine