(138) A Case of Clozapine Toxicity Associated with an NSTEMI and Pericardial Effusion

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Background: Although clozapine is an FDA-approved atypical antipsychotic medication for treatment-resistant ‎schizophrenia, it is not the first-line drug of choice due to its range of adverse side effects, including seizures, ‎myocarditis, and paralytic ileus. Lesser-known reported side effects of clozapine are non-ST-elevation myocardial ‎infarctions (NSTEMIs) and pericardial effusions in the absence of myocarditis (De Fazio, 2015). The following case ‎highlights a complex presentation of clozapine toxicity with atypical cardiac findings of an NSTEMI and worsening ‎pericardial effusion.‎

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Case: The patient is a 58-year-old man with a past psychiatric history of schizophrenia and past medical history ‎of hypertension, hyperlipidemia, type II diabetes mellitus, hypothyroidism, and pericardial effusion without ‎tamponade (diagnosed one year ago) who was medically hospitalized after having two days of shortness of breath, ‎generalized weakness, and lightheadedness.‎

The patient had a transaminitis and elevated cardiac enzymes, likely secondary to a late presentation of an NSTEMI. A ‎pericardial window was performed due to concerns about a chronic pericardial effusion progressing to tamponade. ‎

The patient has been on clozapine for at least ten years prior to admission to better manage psychotic symptoms ‎including disorganized speech, disorganized behaviors, and delusional thinking. His clozapine level on day 1 of ‎admission was 785 ng/ml.‎

Clozapine was discontinued due to concerns that it was contributing to his presentation. The patient had resolution of ‎physical symptoms and was medically cleared after discontinuation of clozapine and the pericardial window. The ‎patient began having worsening psychotic symptoms, including more disorganized behaviors and speech. He was then ‎transferred to an inpatient psychiatric facility for further safety and stabilization.‎

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Discussion: There has been literature suggesting that clozapine is associated with cardiac complications ‎including myocarditis and cardiomyopathy. There are some studies indicating that pericardial effusion is a rare (< ‎‎1:10,000) adverse effect of clozapine, however, less is known about the association between NSTEMIs and clozapine ‎‎(Bath, 2019). In general, pericardial effusions are associated with ST-elevation myocardial infarctions (STEMIs) rather ‎than NSTEMIs, occurring in approximately one-third of STEMIs (Galve, 1986). This case is unique in that it highlights a ‎complex potential association between clozapine toxicity, NSTEMIs, and pericardial effusions.‎

‎Conclusion/Implications: NSTEMIs and pericardial effusions should be considered as possible adverse effects ‎of clozapine toxicity. Consultation-liaison psychiatrists should be mindful of these rare, but important cardiac ‎developments as a sign of clozapine cardiac toxicity even in the absence of myocarditis.‎

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References: ‎
‎1. De Fazio P, Gaetano R, Caroleo M, Cerminara G, Maida F, Bruno A, Muscatello MR, Moreno MJ, Russo E, Segura-‎García C. Rare and very rare adverse effects of clozapine. Neuropsychiatr Dis Treat. 2015 Aug 6;11:1995-2003. doi: ‎‎10.2147/NDT.S83989. PMID: 26273202; PMCID: PMC4532211.‎
‎2. Bath AS, Garg A, Gajare N, Gupta V. Pericardial Effusion: Rare Adverse Effect of Clozapine. Cureus. 2019 Jun ‎‎12;11(6):e4890. doi: 10.7759/cureus.4890. PMID: 31423370; PMCID: PMC6689485‎
‎3. Galve E, Garcia-Del-Castillo H, Evangelista A, Batlle J, Permanyer-Miralda G, Soler-Soler J. Pericardial effusion in the ‎course of myocardial infarction: incidence, natural history, and clinical relevance. Circulation. 1986 Feb;73(2):294-9. doi: ‎‎10.1161/01.cir.73.2.294. PMID: 3943164.‎