A systematic review of clozapine-induced myocarditis

Background: Clozapine is an atypical antipsychotic that is beneficial to some patients who failed to have an adequate clinical response to other antipsychotic drugs. Its clinical use is limited due to several potentially fatal adverse reactions including myocarditis. Careful monitoring of patients on clozapine is required.

Methods: We conducted a systematic review of the literature on myocarditis associated with clozapine therapy. The search engines used to identify cases were MEDLINE, EMBASE, PsycINFO and Cochrane reviews. The references included in the manuscripts reviewed were searched to identify additional reports.

Results: We identified a total of 3347 articles that addressed the cardiac complications of clozapine. Of these, 82 articles detailed cases of clozapine-induced myocarditis. The median age of patients and dose of clozapine at presentation was 30years and 250mg/day respectively. Symptoms and signs of myocarditis developed in 87% of patients within the first month of treatment. Clinical presentation included: shortness of breath (67%), fever (67%) and tachycardia (58%). Cardiac markers were elevated in 87% of the 54 cases that reported these markers. Global ventricular dysfunction was the predominant echocardiogram finding (57%).

Conclusions: Patients on clozapine require routine monitoring for symptoms and signs of myocarditis during the first three months of therapy. This adverse drug reaction is difficult to diagnose due the non-specific nature of the symptoms and signs. Alternate causes of myocarditis should be ruled out before attributing the myocarditis to clozapine.