Atypical antipshycotics (clozapine) are the drugs of choice for schizophrenic patients resistant to major neuroleptics. The widespread clinical use of modern antipsychotic drugs followed the demonstration of the clinical superiority and the lower incidence of neurologic side effects, in particular extrapyramidal symptoms, of clozapine over chlorpromazine in refractory schizophrenia.
Moreover the treatment with clozapine has been demonstrated to be associated with a significant decrease in the risk of suicide. Despite its powerful clinical effects, however, clozapine treatment is associated with a not negligible risk of serious adverse effects, in particular, severe leucopenia to agranulocytosis, dilated cardiomyopathy, myocarditis, pericarditis and, rarely, sudden death. Severe cardiovascular side effects associated with clozapine treatment were initially the object of sporadic case reports, but after a post-marketing surveillance report from the drug manufacturer, careful monitoring for potentially fatal, although uncommon, myocarditis and cardiomyopathy was suggested. Moreover, several cases have been reported from large clinical data-bases. It must be underlined that the diagnosis of cardiac toxicity was usually made only when marked depression of left ventricular function and severe clinical symptoms occurred.
At present, no clinical investigation has assessed the potential sub clinical cardiac toxicity of clozapine. In the last five years we followed more than 60 psychotic patients without history of heart disease, aged less than 50 years, in chronic treatment with clozapine referred from the Florence Psychiatry Department.
Three young males suffering from long-standing psychiatric disorders developed severe left ventricular dysfunction in absence of other significant risk factors other than long-term clozapine treatment.