Incidence and Management of Clozapine-Induced Myocarditis in a Large Tertiary Hospital

Abstract

Objective: Clozapine, an antipsychotic reserved for management of treatment-resistant schizophrenia, is associated with severe adverse effects, including myocarditis. This study aims to determine the incidence of clozapine-induced myocarditis at a large tertiary hospital compared to what is reported in the literature. Methods: Medical records of adult patients admitted to psychiatry units receiving clozapine between January 1, 2010, and July 31, 2016, were retrospectively reviewed. Cases of clozapine-induced myocarditis were defined as having elevated C-reactive protein (CRP) or detectable troponin and at least 1 sign or symptom of myocarditis, in the absence of alternative plausible aetiologies. The primary outcome was incidence of clozapine-induced myocarditis during the study period. Secondary outcomes included rate and description of the management of clozapine-induced myocarditis. Results: In total, 316 patients were screened; 10 patients met the case definition for clozapine-induced myocarditis. The incidence of this adverse drug reaction over the study period was 3.16%. Reduced left ventricular ejection fraction was observed in 60% of cases, and electrocardiography changes were noted in 60% of cases. Clozapine was discontinued in all cases. Rechallenge was performed in 2 patients; recurrent CRP elevation resulted in discontinuation in each case. Medications for management of myocarditis were used in 50% of cases. Although 2 patients required transfer to critical care, the in-hospital mortality rate was 0%. Conclusions: The incidence of clozapine-induced myocarditis at the study hospital was consistent with the higher range reported in the literature. Further research is necessary to elucidate risk factors, definitive diagnostic criteria, and effective management of clozapine-induced myocarditis. Abré gé Objectif : La clozapine, un antipsychotique réservé à la prise en charge de la schizophrénie réfractaire au traitement, est associée à des effets indésirables graves, dont la myocardite. Cette étude vise à déterminer l'incidence de la myocardite induite par clozapine dans un grand hô pital de soins tertiaires comparativement à ce que déclare la littérature.

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

“…Online supplementary Box S9 [38, 66,162,[174][175][176][177][178][179] describes our model of clozapine-induced myocarditis as a hypersensitivity reaction similar to when rapid titrations of lamotrigine induce Stevens-Johnson syndrome and how to prevent it. Online supplementary Box S10 [16,21,26,27,33,36,45,46,48,50,54,58,69,87,[180][181][182][183][184][185][186][187] further describes the published data supporting this model in which rapid clozapine titration is key to explaining clozapine-induced myocarditis. Any titration that is too fast for a specific patient can cause clozapine-induced myocarditis or, more correctly, any kind of clozapine-induced inflammation [66].…”

Cardiovascular side effects of neuropsychiatric medication: an update

“…The clinical symptoms of myocarditis included fever, influenza-like symptoms, nausea, dizziness, sometimes chest discomfort, and patients with cardiomyopathy present heart failure symptoms, but there were reported fatal cases without symptoms. Paraclinically, it was observed the rise in eosinophil cells, presence of inflammatory markers, troponins T and I, creatine-kinase MB, natriuretic peptides, non-specific ECG abnormalities and systolic dysfunction with reduction of the left ventricular ejection fraction 65,66 . In a prospective study, patients treated with clozapine presented subclinical CVSEs demonstrated by early echocardiographic changes, diastolic dysfunction, high systolic pressure in pulmonary artery, without correlation with the modification of other biomarkers 67 .…”

Isolated nausea and vomiting as the cardinal presenting symptoms of clozapine-induced myocarditis: a case report

“…Due to underdiagnoses and a lack of shared standardized diagnostic approach worldwide, the true incidence of myocarditis remains unclear [ 8 ]. In patients using clozapine the reported incidence worldwide varies from < 0.1 to 3.2% [ 4 , 5 , 9 ]. In Australia incidence rates up to 8.5% are reported, possibly due to genetic factors, geographical differences and/or greater awareness and monitoring [ 10 – 12 ].…”