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

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 ob...

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Bibliographic Details
Published in:BMC Psychiatry
Main Authors: Ingimarsson, Oddur, Maccabe, James H., Haraldsson, Magnús, Jónsdóttir, Halldóra, Sigurdsson, Engilbert
Format: Article in Journal/Newspaper
Language:English
Published: 2016
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Online Access:https://kclpure.kcl.ac.uk/portal/en/publications/neutropenia-and-agranulocytosis-during-treatment-of-schizophrenia-with-clozapine-versus-other-antipsychotics-an-observational-study-in-iceland(502b0b90-c06b-4c0b-aab7-9e1d4cbe6c68).html
https://doi.org/10.1186/s12888-016-1167-0
https://kclpure.kcl.ac.uk/ws/files/62465712/Neutropenia_and_agranulocytosis_during_Ingimarsson_Accepted_9DEC2016_GOLD_VoR_CCBY.pdf
http://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-016-1167-0
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Summary: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 ...