Clozapine-induced agranulocytosis
- PDF / 275,634 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 49 Downloads / 169 Views
REVIEW ARTICLE
Clozapine-induced agranulocytosis Aleksandar Mijovic 1
&
James H. MacCabe 2
Received: 26 April 2020 / Accepted: 10 August 2020 # The Author(s) 2020
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. Keywords Clozapine . Agranulocytosis . Re-challenge . Ethnic neutropenia
Introduction Drug-induced agranulocytosis is a potentially life-threatening, idiosyncratic reaction characterized by a profound decrease in neutrophil count and susceptibility to infection. Among the many causative agents, antipsychotic drug clozapine occupies a unique place due to its role in treatment-refractory schizophrenia (TRS), where it is often the only effective treatment [1]. Clozapine-induced agranulocytosis (CLIA) is an obstacle to clozapine use in a much larger number of patients with schizophrenia. Clozapine (CZP), a dibenzodiazepine atypical antipsychotic drug, was introduced for treatment of schizophrenia in Europe in 1971, rapidly gaining popularity due to its efficacy and virtual absence of extrapyramidal side effects [2]. However, its propensity to cause neutropenia and agranulocytosis was soon recognized [3], leading to its withdrawal. A double-blind, randomized trial, which demonstrated superior
* Aleksandar Mijovic [email protected] 1
Department of Haematological Medicine, King’s College Hospital, London SE5 9RS, UK
2
Institute of Psychiatry, King’s College London, London, UK
efficacy of CZP over chlorpromazine [4] in TRS, led to its reintroduction in 1989 in Europe and in 1990 in the USA. However, CZP use is largely restricted to treatment-resistant cases and blood count monitoring, mandatory for the entire duration of treatment, has been introduced in most countries. The National Institute for Clinical Excellence 2014 guidelines state that CZP is the drug of choice for treatment-resistant psychosis, defined as failure to respond to at least two other trials of a
