Clozapine Pharmacogenetic Studies in Schizophrenia : Efficacy and Agranulocytosis

Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis.

© 2018 Numata, Umehara, Ohmori and Hashimoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)(https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.