Immunomodulatory effects of clozapine and their clinical implications: What have we learned so far?

Managing clozapine-induced neutropenic fever: A case report

“…She also presented oliguria (urine output < 0.5 mL/kg/h) and signs of poor peripheral perfusion (cold extremities, cyanosis, and capillary refill time > 2 s). The complete blood cell count demonstrated leukopenia (total leukocyte count 410 cells/mm 3 ) and profound neutropenia (absolute neutrophil count 60 cells/mm 3 ) with no abnormalities in hemoglobin or platelet counts. Initial C-reactive protein was elevated (96 mg/L) as was serum creatinine and BUN (3.5 mg/dL and 62 mg/dL, respectively).…”

“…After results of the antimicrobial susceptibility tests, vancomycin treatment was suspended given that there was no evidence of infection by gram-positive bacteria. After the fifth day of treatment, neutrophil counts began to increase, and reached values above 500 cells/mm 3 after the eighth day. The antimicrobial treatment with piperacillin-tazobactam was maintained for 14 days, and the patient was extubated on the tenth day.…”

“…the patient rapidly developed cardiorespiratory collapse requiring mechanical ventilation and vasoactive drugs few minutes after arrival at hospital. Profound neutropenia (absolute neutrophil count 60 cells/mm 3 ) and lobar pneumonia were diagnosed. broad- spectrum antimicrobial therapy with piperacillintazobactam plus vancomycin and supportive intensive care were promptly implemented.…”

“…The estimated incidence of clozapine-induced neutropenia ranges from 0.5-2.0% of patients treated with this medication, with the majority of cases occurring within the first three months after the start of treatment [2]. Although the exact mechanism of neutrophil toxicity is unknown, some evidence suggests immunologically mediated reactions may play a role [3]. Neutropenic fever (NF) is a syndrome characterized by fever in the presence of neutropenia (absolute neutrophil count < 500 cells/mm 3 ) [4].…”

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

“…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. …”