Clozapine-induced myocarditis: Separating the wheat from the chaff

To the Editor,

There has been increased awareness of clozapine-induced myocarditis since the publication of the review of fifteen clozapine-induced myocarditis cases reported to the Australian Adverse Drug Reaction Committee (Kilian et al., 1999). Rates of clozapine-induced myocarditis appear to be higher in Australia than in other countries (Lambert, 2010: 24). Whilst recognition of this problematic adverse effect is encouraged, concern has been raised about possible over diagnosis (Ronaldson et al., 2010). Misdiagnosis may be due to two factors: insufficient data to support a diagnosis of myocarditis; or where there is sufficient data to support the diagnosis but there is an alternative primary cause such as a viral respiratory tract infection.

We recently reviewed 20 cases with a recorded diagnosis of clozapine-induced myocarditis at a large tertiary referral hospital in Brisbane (reported between 2005 and 2013). We reviewed clinical information in the patient’s chart against the comprehensive set of diagnostic criteria for clozapine-induced myocarditis developed by Ronaldson et al. (2010).

We found that 13/20 (65%) cases did not meet the Ronaldson criteria for a diagnosis of clozapine-induced myocarditis. Whilst an elevated troponin was present in 17/20 (85%) cases, other parameters were either not assessed or not indicative of myocarditis. Electrocardiogram abnormalities were only present in 12/20 (60%) cases, fever in 12/20 (60%) and a heart rate >100bpm in 11/20 (55%) cases. Additionally, 5/20 (25%) cases had documented upper respiratory tract infections, which was an alternate possible cause of the myocarditis. No cardiac MRI or cardiac biopsies were performed in any of these cases.

These findings suggest that the veracity of the diagnoses of clozapine-induced myocarditis may be suboptimal. Appropriate clinical investigations to clarify and confirm the diagnosis were not done, or not recorded in clinical notes. There are substantial short and long term ramifications of clozapine cessation in people with treatment resistant schizophrenia including acute relapse of psychotic symptoms, deterioration in function and loss of access to the gold standard treatment. Close communication between psychiatrists and cardiologists is essential to reduce the risk of inappropriate myocarditis diagnosis. People with treatment resistant schizophrenia who have ceased clozapine following a presumptive diagnosis of clozapine-induced myocarditis may benefit from revisiting this diagnosis. If the diagnosis of clozapine-induced myocarditis is in question, they may be eligible for a closely monitored clozapine rechallenge.