Beyond Clozapine: Myocarditis and Cardiomyopathy Associated with Antipsychotic Medications—An Updated Narrative Review for Psychiatric Practice

Background

Antipsychotic medications are associated with increased cardiovascular morbidity and mortality in patients with serious mental illness (SMI). Clozapine-induced myocarditis and cardiomyopathy are well established; however, emerging pharmacovigilance and observational data suggest that cardiotoxic risk extends beyond clozapine to other antipsychotic agents.

Methods

We conducted a narrative review of the literature (2000–2026), including pharmacovigilance databases (VigiBase, FAERS), cohort studies, case series, and consensus guidelines. Emphasis was placed on epidemiology, mechanisms, comparative risk, clinical presentation, diagnosis, and practical management strategies relevant to psychiatric practice.

Results

Clozapine demonstrates the highest risk of myocarditis (estimated incidence 0.3–3%), typically within the first 4–8 weeks of treatment. Pharmacovigilance data consistently identify secondary signals for quetiapine and olanzapine, with weaker but present associations for risperidone, aripiprazole, and other agents. Proposed mechanisms include hypersensitivity myocarditis, inflammatory cytokine activation, oxidative stress, and mitochondrial dysfunction. Early recognition through symptom monitoring and selective biomarker use significantly improves outcomes.

Conclusions

Cardiotoxicity associated with antipsychotics is not limited to clozapine. Psychiatrists should adopt a risk-stratified approach incorporating cautious titration, early symptom recognition, and targeted monitoring. Greater awareness and multidisciplinary collaboration are essential to optimize both psychiatric and cardiovascular outcomes.