Clozapine-induced agranulocytosis

Abstract

Wider use of clozapine, one of the most effective antipshychotic drugs, is precluded by its propensity to cause agranulocytosis. Currently, clozapine is used for treatment-resistant schizophrenia, with mandatory blood count monitoring for the duration of treatment. Agranulocytosis occurs in up to 0.8% of patients and presents a significant medical challenge, despite decreasing mortality rates. In this paper, we review the epidemiology of clozapine-induced agranulocytosis (CLIA), advances in identifying genetic risk factors, and the preventive measures to reduce the risk of CLIA. We discuss the pathogenesis of CLIA, which, despite receiving considerable scientific attention, has not been fully elucidated. Finally, we address the clinical management and suggest the approach to clozapine re-challenge in patients with a previous episode of neutropenia. With a significant proportion of clozapine recipients in Western hemisphere being Black, we comment on the importance of recognizing benign ethnic neutropenia as a potential impediment to clozapine administration. This review aims to aid haematologists and psychiatrists to jointly manage neutropenia and agranulocytosis caused by clozapine.

Antidepressants- and antipsychotics-induced hepatotoxicity

“…Regarding SGAs, clozapine was shown to cause severe adverse effects, including metabolic syndrome (Pillinger et al 2020 ) and agranulocytosis (Mijovic 2020 ), as well as hepatotoxicity (Table 2 ). Both metabolic syndrome and agranulocytosis were previously linked to oxidative stress (Fischer et al 1991 ; Ando and Fujita 2009 ).…”

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety—Particularities in the Context of COVID-19

“…The risk of developing agranulocytosis is under 1% in CLZ patients, which may be independent of dosing [ 50 , 51 ], occurring in the first month of the treatment, up to six months; in this time span, it requires extensive blood absolute neutrophil counts [ 52 ]. The link between clozapine and agranulocytosis is still uncertain, with links between drug interactions, the immune system, and the genetic predisposition [ 53 ].…”

Risperidone-Induced Neutropenia in a Schizophrenic Patient: A Case Report and Literature Review

“…In terms of pathophysiology, the documented body of evidence suggests that clozapine-induced neutropenia typically occurs within the first 18 weeks of treatment [ 11 , 12 ], while RIN pathogenesis remains unknown and still needs further studies. Etiologically, using animal studies, it has been hypothesized that risperidone metabolites cause bone marrow suppression.…”