Abstract
Objective: To develop an evidence-based monitoring protocol for clozapine-induced myocarditis.
Methods: Potential cases of clozapine-related myocarditis occurring between January 1994 and January 2009 and a comparative group of patients taking clozapine for at least 45 days without cardiac disease were documented from the patients’ medical records.
Results: A total of 75 cases and 94 controls were included. Nine cases died. The time to onset was 10–33 days with 83% of cases developing between days 14 and 21 inclusive.
At least twice the upper limit of normal troponin was found in 90% of cases, but 5 cases had C-reactive protein more than 100 mg/L and left ventricular impairment by echocardiography without a clinically significant rise in troponin.
The proposed monitoring protocol recommends obtaining baseline troponin I/T, C-reactive protein and echocardiography, and monitoring troponin and C-reactive protein on days 7, 14, 21 and 28. Mild elevation in troponin or C-reactive protein, persistent abnormally high heart rate or signs or symptoms consistent with infective illness should be followed by daily troponin and C-reactive protein investigation until features resolve. Cessation of clozapine is advised if troponin is more than twice the upper limit of normal or C-reactive protein is over 100 mg/L. Combining these two parameters has an estimated sensitivity for symptomatic clozapine-induced myocarditis of 100%. The sensitivity for asymptomatic disease is unknown.
Conclusion: This protocol recommends active monitoring for 4 weeks, relying predominantly on troponin and C-reactive protein results. It encourages continuation of clozapine in the presence of mild illness, but defines a threshold for cessation.
Acknowledgements
The assistance of Sally Wilson in documenting some of the control patients is gratefully acknowledged. In addition, the authors are grateful for the assistance of individuals at each of the following health services: from Victoria, Austin Health, Barwon Health, Bayside Health, Bendigo Health, Eastern Health, North West Mental Health, Peninsula Health, Southern Health, St Vincent's Health, Thomas Embling Hospital, and Werribee Mercy Mental Health Service; from New South Wales, Northern Sydney Central Coast Health, Sydney South West Area Health Service, Wandene Private Hospital and private psychiatrist Chris McDowell; and from Queensland, Prince Charles Hospital.
Declaration of interest: Kathlyn Ronaldson received a salary in 2006 and 2007 from a grant from the Australian National Health and Medical Research Council (NHMRC). Paul Fitzgerald is supported by an NHMRC Practitioner Fellowship. The authors alone are responsible for the design and analysis of this study for the writing and content of this article.