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Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland


Titill: Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland
Höfundur: Ingimarsson, Oddur
MacCabe, James   orcid.org/0000-0002-6754-1018
Haraldsson, Magnús
Jónsdóttir, Halldóra
Sigurdsson, Engilbert   orcid.org/0000-0001-9404-7982
Útgáfa: 2016-12
Tungumál: Enska
Umfang: 441
Háskóli/Stofnun: Háskóli Íslands
University of Iceland
Svið: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Deild: Læknadeild (HÍ)
Faculty of Medicine (UI)
Birtist í: BMC Psychiatry;16(1)
ISSN: 1471-244X
DOI: 10.1186/s12888-016-1167-0
Efnisorð: Schizophrenia; Clozapine; Antipsychotics; Neutropenia; Agranulocytosis; Geðklofi; Geðlyf; Blóðsjúkdómar
URI: https://hdl.handle.net/20.500.11815/381

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Tilvitnun:

Ingimarsson, O., MacCabe, J. H., Haraldsson, M., Jónsdóttir, H., & Sigurdsson, E. (2016). Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland. BMC Psychiatry, 16(1), 441. doi:10.1186/s12888-016-1167-0

Útdráttur:

Background Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. Methods The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. Results The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500–1900 neutrophils/mm3). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500–1400 /mm3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Conclusions Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.

Leyfi:

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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