Myocarditis Related to Clozapine Treatment

Abstract

Myocarditis has in several case reports been associated with use of clozapine. Eight cases of myocarditis during treatment with clozapine that were submitted to the Swedish Adverse Drug Reaction Advisory Committee and 18 cases that were reported in the literature are summarized. As part of the routine signal detection process on the World Health Organization (WHO) Program on International Drug Monitoring database, which contains more than two million case reports of spontaneously reported suspected adverse drug reactions, a Bayesian confidence propagation neural network (BCPNN) is used. This article also shows the retrospective output of the BCPNN over time for clozapine and myocarditis and discusses its implications. In 19 (79%; duration of treatment not stated for 2 patients) of 24 patients with myocarditis, the symptoms occurred within the first 6 weeks of clozapine treatment. Many patients shared a similar clinical course, with symptoms such as an influenza-like illness, fever, sinus tachycardia, hypotension, chest discomfort, and heart failure. The reaction was fatal in 12 (46%) of these patients. The other patients generally had a prompt recovery. By using the BCPNN technique, a quantitative association between clozapine and myocarditis was demonstrated, and the association might have been high-lighted for clinical review in 1994 had this BCPNN method been in use at the WHO center at the time. Myocarditis seems to be a rare and potentially lethal adverse effect of clozapine. Admittance for observation, interruption of the clozapine treatment, and treatment with corticosteroids should be considered for patients in whom this reaction is suspected.

Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns?

“…Albeit the known correlation between schizophrenia and increased cardiovascular mortality it may difficult to estimate the sudden death due to particular neuroleptics at therapeutic doses [ 135,136 ]. Clozapine beyond the well-known agranulocytosis risk, is being associated with myocarditis, cardiomyopathy and arrhythmogenesis risk [ 137,138 ]. It also reduced measures of heart rate variability associated with parasympathetic control [ 124 ].…”

Clozapine-Induced Myocarditis: Recognizing a Potentially Fatal Adverse Reaction

“…9 Early recognition of the condition-and prompt discontinuation of the offending agent-are crucial. Lower patient exposures to clozapine are associated with lower mortality rates.…”

Sudden cardiac death and antipsychotics. Part 1: Risk factors and mechanisms

“…Case reports linking antipsychotic drugs and cardiac arrhythmia have appeared for thioridazine (Liberatore & Robinson, 1984;Donatini et al, 1992), pimozide (Committee on Safety of Medicines, 1990), sulpiride, droperidol, haloperidol (Kriwisky et al, 1990;Jackson et al, 1997), sertindole (Committee on Safety of Medicines, 1999), risperidone (Zarate et al, 1997), ziprasidone (Adolfsson & Lindblom, 2002) and clozapine (Killian et al, 1999;Hägg et al, 2001). Clozapine has also been linked with potentially fatal myocarditis and cardiomyopathy in physically healthy young adults with schizophrenia.…”

“…Since 1980 at least 213 cases of myocarditis in people taking clozapine have been reported in the literature, with at least 50 fatalities (Hägg et al, 2001;Merrill et al, 2005). In some series about half of cases of clozapine-induced myocarditis are fatal, and about a quarter of these people die suddenly.…”