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Sodium valproate and clozapine induced neutropenia: A case control study using register data.

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posted on 22.11.2019 by Steffi Malik, John Lally, Olesya Ajnakina, Megan Pritchard, Amir Krivoy, Fiona Gaughran, Hitesh Shetty, Robert J. Flanagan, James H. MacCabe

BACKGROUND: The use of clozapine is limited due to the occurrence of neutropenia, and the rare but life threatening adverse event of agranulocytosis. There is little epidemiological research into clinical factors that may impact on this risk. We conducted a case control study examining the clinical risk factors for neutropenia patients treated with clozapine.

METHOD: A case-control study was conducted within a database of anonymised electronic clinical records. All patients who discontinued clozapine due to a neutropenic event were included as cases. Matched controls were selected from patients with a documented clozapine exposure at the time of the clozapine neutropenic event of the case patient, matched by duration of clozapine treatment.

RESULTS: 136 cases and 136 controls were included. In multivariable analysis, the concurrent use of sodium valproate was associated with neutropenia (Odds Raito (OR) 2.28, 95%CI: 1.27-4.11, p=0.006). There was a dose-response effect, with greater associations for higher doses. Patients who discontinued clozapine due to neutropenia were more likely to be of black ethnicity (OR 2.99, p

CONCLUSION: We identified an association between the concurrent use of sodium valproate and an increased risk of clozapine associated neutropenia. These results, taken in combination with the results from previous case series, suggest that the risk of clozapine associated neutropenia could be reduced by avoiding concurrent valproate treatment.

Funding

National Institute forHealth Research (NIHR) Biomedical Research Centre at South London. Maudsley NHSFoundation Trust and King's College London.

History

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The original article is available at https://www.sciencedirect.com

Published Citation

Malik S, Lally J, Ajnakina O, Pritchard M, Krivoy A, Gaughran F, Shetty H, Flanagan RJ, MacCabe JH. Sodium valproate and clozapine induced neutropenia: A case control study using register data. Schizophrenia Research. 2018;195:267-273.

Publication Date

01/05/2018

Publisher

Elsevier

PubMed ID

28882687

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