Clozapine-related Sudden Pericarditis in a Patient Taking Long Acting Aripiprazole and Valproate: A Case Report

Abstract

Clozapine may be associated with cardiovascular adverse effects including QTc prolongation and, more rarely, with myocarditis and pericarditis. Although rare, these latter cardiovascular adverse effects may be life-threatening and must be immediately recognized and treated. Several cases of clozapine related-pericarditis have been described and often it has a subtle and insidious onset with symptoms that may be often misdiagnosed with psychiatric manifestations (e.g. anxiety, panic or somatization) leading to a delayed correct diagnosis with potential fatal consequences. In the present report we describe the case of a 27-year-old girl with schizoaffective disorder taking long acting aripiprazole and valproate who developed a sudden onset clozapine-related pericarditis during titration phase that resolved with immediate clozapine discontinuation and indomethacin administration. We underline the importance of an early diagnosis of clozapine-related pericarditis and the need to have monitoring protocols to prevent this potentially fatal adverse effect especially when polypharmacy is administered to patients taking clozapine.

Clozapine-Induced Cardiotoxicity Presenting as Sepsis: A Case Report and Literature Review

“…The mechanism of clozapine myocarditis has not been established in the literature, but IgE-mediated hypersensitivity, genetic predisposition, and cholinergic dysfunction have been proposed as possible causes [10]. The common presenting symptoms are shortness of breath, palpitations, cough, and fatigue [8]. Kilian et al reviewed 8000 patients on clozapine and reported 23 cases of myocarditis and cardiomyopathy and cited fever in association with chest pain or dyspnea as a presenting symptom, but fever as a sole presenting symptom has not been reported [12].…”

“…It has a reported incidence of 3% and may lead to cardiomyopathy [7]. Clozapine-induced pericarditis has also been reported and should be considered as a differential as in a recent case described by Berardis and colleagues in 2018 of a 27-year-old woman with schizoaffective disorder, who developed a sudden onset clozapine-related pericarditis during medication titration [8]. Our present case is that of a young African American man who was transferred from an inpatient psychiatric unit due to suspected sepsis as he met the systemic inflammatory response syndrome (SIRS) criteria and treated accordingly with antibiotics but a closer review of an increasing eosinophilia, a high troponin, the context of his current clozapine regimen, and absence of other clinical explanation of his symptomatology prompted a revision of the diagnosis to myocarditis probably induced by clozapine.…”

Possible involvement of apoptosis in the antipsychotics side effects: A mini‐review

“…However, it has been shown in animal models that CLZ‐induced cardiotoxicity is accompanied by a higher number of cardiac cells showing immunoreactivity for activated caspase 3 in the cytoplasm, DNA damage, apoptosis, increased myocardial oxidative stress and inflammatory cytokines, with attenuation in antioxidant defences 56 . However, it is important to point out that CLZ‐induced cardiac complications may be caused by several risk factors, which include rapid dose titration, presence of weight gain or metabolic adverse effects, co‐administration of selective serotonin reuptake inhibitors, use of illicit substances or concomitant treatment with some medications 57–59 . Although the risk of developing a CLZ‐related myocarditis is relatively low, all the possible risk factors should be taken into account when considering treatment.…”

“…56 However, it is important to point out that CLZ-induced cardiac complications may be caused by several risk factors, which include rapid dose titration, presence of weight gain or metabolic adverse effects, co-administration of selective serotonin reuptake inhibitors, use of illicit substances or concomitant treatment with some medications. [57][58][59] Although the risk of developing a CLZ-related myocarditis is relatively low, all the possible risk factors should be taken into account when considering treatment.…”

The disquietude of clozapine continuation during the COVID‐19 pandemic

“…Serial MB isoenzyme of creatine phosphokinase (CPK-MB), C-reactive protein (CRP), troponin test, and ECG is advised in order to determine any sign which refers to a cardiac event. 12,13 Clozapine-induced cardiac complications may be missed and delayed presenting to services due to the similarity with the symptomatology of the COVID-19. A delay could lead to serious consequences such as clozapine-induced myocarditis has an estimated mortality of more than 20%.…”