Abstract:
Clozapine-associated myocarditis usually presents within the first 18 weeks of clozapine therapy and is acute in nature whereas cardiomyopathy may take months or years to manifest. Despite the fact that they are long recognized as problematic, with careful clinical management of patients required, neither the true incidence of these cardiotoxicities nor the relationships with clozapine exposure are known. Myocarditis presents with symptoms that can mimic viral illness and are detectable on laboratory investigations. Cardiomyopathy presents with general signs and symptoms that include the gradual onset of shortness of breath on exertion, swollen ankles and fatigue. The causative role of clozapine is determined after excluding alternative causes such as myocardial ischemia or alcoholic cardiomyopathy. There is a lack of standardization for the criteria used to diagnose clozapine-associated cardiotoxicity and cardiologists will sometimes make arbitrary decisions to discontinue clozapine if there is uncertainty. This deprives patients of what can be a life-changing drug. This study is a series of clinical investigations to determine both the incidence of clozapine-associated cardiotoxicity and potential risk factors in patients currently taking clozapine and in patients who have died while taking clozapine. A clinical review of patient records was conducted to determine the incidence of the development of myocarditis using recommended ADHB criteria. Approximately 4% of patients initiating clozapine were diagnosed with myocarditis. However, more patients had clozapine therapy stopped due to increases in laboratory markers for cardiotoxicity, although myocarditis was not recorded as a diagnosis. The Coronial autopsy database in ADHB was searched between the years 2001-2015 using the word search parameters cardiomyopathy, myocarditis and clozapine. Each autopsy report was reviewed and available clinical laboratory results for clozapine levels, lipid profile, liver enzyme profile and diabetes markers were collated. Our initial data suggests that patients on clozapine die several years younger than individuals who die from cardiotoxicity with the same co-morbidities. Additionally high levels of clozapine in our cases at the time of death may be misleading and most likely represent post-mortem redistribution.