Clozapine-Associated Pericarditis: A Systematic Review

Abstract

Background: Clozapine is an atypical antipsychotic for treatment-resistant schizophrenia. Despite its efficacy, it is associated with many serious side effects, including pericarditis. Clozapine-associated pericarditis may range from mild symptoms to life-threatening complications. Despite increasing case reports, a comprehensive synthesis is lacking, necessitating a systematic review.

Objective: To systematically summarize and analyze published case reports of clozapine-assoicated pericarditis with a focus of clinical presentation, diagnostic findings, treatment approaches and patient outcomes.

Methods: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered in International Prospective Register of Systematic Reviews. Eight databases, including PubMed, Embase, and PsycINFO, were searched, identifying case reports published between 1980 and 2024. Inclusion criteria focused on English-language case reports diagnosing clozapine-associated pericarditis. Exclusion criteria included nonclozapine-associated pericarditis and mixed etiologies without clozapine-specific data. Data extraction included demographics, clinical presentation, diagnostic findings, management, and outcomes.

Results: The mean age was 33.56 years, with males comprising 63.9%. Fever (52.8%), breathlessness (50%), and tachycardia (44.4%) were the most common symptoms. Diagnostic tests consistently indicated elevated inflammatory markers, including C-reactive protein (mean: 88.13 mg/dL) and erythrocyte sedimentation rate (mean: 72.72 mm/h). Echocardiograms confirmed pericardial effusion in 88.9% of cases. Management strategies included colchicine (16.7%) and analgesics (19.4%), with cardiac recovery achieved in all but one case. Clozapine rechallenge was attempted in 16.7% of the cases, with successful outcomes in 83.3% of these cases.

Conclusions: Clozapine-associated pericarditis is a rare but serious adverse event characterized by elevated inflammatory markers and diagnostic imaging abnormalities. Prompt recognition and tailored management, including anti-inflammatory treatment and careful rechallenge, can lead to favorable cardiac and psychiatric outcomes.

Keywords: cardiotoxicity: treatment-resistant schizophrenia; clozapine; clozaril: antipsychotic side effects; pericarditis.