Update on the Adverse Effects of Clozapine: Focus on Myocarditis

Abstract

Clozapine, an atypical antipsychotic, is a dibenzodiazepine derivative and its therapeutic effects are probably mediated by dopaminergic and serotonergic activity. In accordance to several studies, it appears to be the most effective antipsychotic drug for treatment-resistant schizophrenia. Moreover, clozapine appears to be particularly beneficial in patients with schizophrenia who are suicidal and in those with comorbid substance use disorder. However, despite its efficacy, the general use of clozapine in clinical practice is somewhat limited because of the risk of several serious adverse effects such as agranulocytosis and thromboembolism. Clozapine may be associated with fatal myocarditis and cardiomyopathy in physically healthy young adults. Consequently, the FDA and the drug's manufacturer have strengthened warnings to include that a potentially fatal myocarditis may occur when taking clozapine. In the present paper the literature on clozapine-related myocardis will be reviewed and practical advice will be given concerning the diagnosis and management of such potentially fatal adverse effect.

An update of safety of clinically used atypical antipsychotics

“…Clozapine may be associated with the occurrence of severe cardiovascular AEs including dilated cardiomyopathy/myocarditis/pericarditis [87]. Dilated cardiomyopathy is an uncommon, but potentially LT AEs following clozapine treatment, which may be confused with myocarditis and may develop also after a long-term therapy [87].…”

Safety and Tolerability of Antipsychotics

“…The total number of cases reported from this study for myocarditis from CLZ was 231 cases versus 89 cases from all other antipsychotics. The incidence of CLZ-induced myocarditis ranges between 1 in 1,000 and 1 in 10,000 patients with 213 cases (including 50 fatalities) that occurred in the fi rst 2 months of therapy (Berardis et al 2012 ). CLZ dose was an independent factor.…”

“…CLZ dose was an independent factor. Recommendations for myocarditis detection includes weekly ECGs, C-reactive protein (CRP), and troponin laboratory testing matched with vital signs and clinical symptomatology for the fi rst 4 weeks of CLZ therapy (Berardis et al 2012 ;Munshi et al 2014 ). Afterward, vital signs and clinical symptoms can be closely followed for the next few months.…”

Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study

“…5 Not only is clozapine underused; its prescription is decreasing in some countries, and initiation is delayed. [6][7][8][9][10] The reasons for this reduction range from the life-threating risks of agranulocytosis 11 and myocarditis 12 to highly disturbing hypersialorrhea 13 and constipation.…”