Cardiovascular Disease in Clozapine-Treated Patients: Evidence, Mechanisms and Management

Myocarditis occurs in about 3% of those initiated on clozapine but monitoring reduces the risk of serious outcome. Cardiomyopathy may develop after myocarditis, or from prolonged tachycardia. Monitoring using echocardiography is not deemed cost effective. Tachycardia, orthostatic hypotension and reduced heart rate variability are a group of clozapine-related adverse effects associated with autonomic dysfunction and may have serious consequences in the long term. Elevated heart rate and poor heart rate variability can be treated with a β-blocker or a non-dihydropyridine calcium channel blocker, while orthostatic hypotension can be alleviated by increased fluid intake and abdominal binding, but may require pharmacological intervention. Adequate correction for heart rate may show that clozapine does not prolong the QT interval. Other cardiovascular effects, pulmonary embolism, metabolic syndrome, sudden cardiac death and particularly the excessive mortality from cardiovascular disease events may be more strongly associated with the combination of mental illness, lifestyle factors and poor treatment of cardiovascular disease and its risk factors than with clozapine treatment. In view of the efficacy of clozapine and the evidence of reduced mortality relative to other antipsychotics, clozapine should be prescribed when indicated and recipients should be enrolled in lifestyle programmes to increase exercise and improve diet, and referred for diagnosis and treatment of cardiovascular disease and its risk factors.