Management of Clozapine Titration in the Setting of Cardiac Comorbidities

Treatment-resistant schizophrenia is commonly treated by the initiation of Clozapine therapy. Clozapine (Clozaril) has a wide side effect profile with significant mortality stemming from early myocarditis or late cardiomyopathy. This risk profile is complicated in those with preexisting comorbidities. A 67-year-old male with a decade-long history of paranoid schizophrenia. His previous treatment regimen consisted of a combination of Haloperidol-Decanoate, Aripiprazole, and Olanzapine. On his most recent admission, the patient presented with an acute exacerbation of his schizophrenia with incontinence, agitation, and difficulty following commands. Due to the refractory nature of his symptoms, Clozapine therapy was initiated. During this time serial C-reactive protein (CRP) measurements increased markedly. This increase was seen in the context of worsening lower leg edema and air hunger. Clozapine taper was held, and the medical team was consulted. The consultation resulted in an echocardiogram showing signs of diastolic failure with an unknown etiology. Subsequent CT chest, however, ruled out any pericardial pathology and eliminated suspicion for clozapine-induced myocarditis. Clozapine taper was then restarted. When beginning clozapine in a patient with underlying cardiac risk factors, it is paramount to take into consideration the patient's baseline cardiopulmonary function. This report outlines the necessity of a baseline echocardiogram for patients with severe cardiac comorbidities. This in turn may have prevented a four-day delay of clozapine titration. Earlier and more frequent CRP measurements titration would have also guided clinical assessment as well. Furthermore, this case stresses the larger implications of investigating medical comorbidities among patients presenting on a psychiatric unit.