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Establishing the characteristics of an effective pharmacogenetic test for clozapine-induced agranulocytosis

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)461-466
Number of pages6
JournalThe pharmacogenomics journal
Issue number5
Early online date3 Mar 2015
E-pub ahead of print3 Mar 2015
Published24 Oct 2015

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© 2015 Macmillan Publishers Limited All rights reserved 1470-269X/15


  • Verbelen_et_al_2015

    Verbelen_et_al_2015.pdf, 570 KB, application/pdf

    Uploaded date:19 Aug 2015

    Version:Final published version

    Licence:CC BY

King's Authors


Clozapine is the only evidence-based therapy for treatment-resistant schizophrenia, but it induces agranulocytosis, a rare but potentially fatal haematological adverse reaction, in less than 1% of users. To improve safety, the drug is subject to mandatory haematological monitoring throughout the course of treatment, which is burdensome for the patient and one of the main reasons clozapine is underused. Therefore, a pharmacogenetic test is clinically useful if it identifies a group of patients for whom the agranulocytosis risk is low enough to alleviate monitoring requirements. Assuming a genotypic marker stratifies patients into a high-risk and a low-risk group, we explore the relationship between test sensitivity, group size and agranulocytosis risk. High sensitivity minimizes the agranulocytosis risk in the low-risk group and is essential for clinical utility, in particular in combination with a small high-risk group.

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