Clozapine Associated with Autoimmune Reaction, Fever and Low Level Cardiotoxicity – A Case Report

Abstract

Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia (1, 2). Despite its effectiveness, this drug is not without adverse effects, highgrade fever and cardiotoxicity being among them, through its immunomodulatory effects (3). Clozapine-induced fever has been reported by several studies and a number of plausible explanations for the induction of fever exist including the implication of the immune-modulating effect by increasing soluble tumor necrosis factor (TNF) receptor p55, p75 and soluble interleukin-2 (IL2) receptor (4, 5). IL6 has also been suggested to induce fever by elevating the set point of body core temperature via temperature-sensitive neurons in the preoptic area of the hypothalamus (6), for example as a result of pyrogenic cytokines (7). Likewise, drug-induced cardiotoxicity has many underlying mechanisms, affecting the heart directly and, in other cases, indirectly, including the enhancement of immunological reactions, cell apoptosis, formation of free radicals and alterations of hemodynamic flow. Several preclinical and clinical reports have shown the relation of a high incidence of clozapine-induced myocarditis (3,4,8) with immunological-mediated mechanisms.Here we present the case of a 31-year-old Caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein (CRP) and high sensitivity (Hs)-troponin levels, without presenting any other signs of myocarditis, on the 13th day under clozapine treatment, all of which declined progressively upon discontinuation of the drug. Case ReportA 31-year-old Caucasian male with no significant past medical history, besides heavy smoking and abusing marijuana, was 141

Machine Learning for Predicting Risk of Drug-Induced Autoimmune Diseases by Structural Alerts and Daily Dose

“…For instance, clozapine was reported to be associated with drug-induced ADs [ 52 , 53 ] and can form an iminium reactive metabolite that could covalently bind to glutathione or other proteins [ 54 ] ( Supplemental Figure S5 ). Reactive metabolite formation is dependent on the nitrogen that bridges the two rings [ 55 ].…”

Clozapine-induced myocarditis

“…Early detection of CIM and the taking of appropriate measures may lead to the complete resolution of clinical symptoms [100], though the changes associated with CIM can be observed only by means of additional tests [82,95]. In some people a significant impairment of the heart can occur as a consequence of CIM [101].…”

“…Wczesne wykrycie CIM i podjęcie odpowiednich działań może prowadzić do całkowitego ustąpienia objawów klinicznych [100], a zmiany związane z wystąpieniem CIM mogą być uchwytne jedynie za pomocą badań dodatkowych [82,95]. U niektórych osób konsekwencją CIM może być znaczne upośledzenie pracy serca [101].…”

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“…The authors 3 mention that clozapine-induced fever is a common adverse effect with an incidence as high as 55% of patients. They note that there seems to be a correlation between the fever and the days after initiation of clozapine.…”