title: Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.
abstract: 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 /mm3of 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.
authors.affiliation: Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland.|Landspitali University Hospital, Mental Health Services, Hringbraut, 101, Reykjavik, Iceland.
authors.forename: Oddur
authors.initials: O
authors.lastname: Ingimarsson
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College, London, UK.|National Psychosis Unit, Bethlem Royal Hospital, South London and Maudsley NHS Foundation Trust, London, UK.
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
authors.affiliation: Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland.|Landspitali University Hospital, Mental Health Services, Hringbraut, 101, Reykjavik, Iceland.
authors.forename: Magnús
authors.initials: M
authors.lastname: Haraldsson
authors.affiliation: Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland.|Landspitali University Hospital, Mental Health Services, Hringbraut, 101, Reykjavik, Iceland.
authors.forename: Halldóra
authors.initials: H
authors.lastname: Jónsdóttir
authors.affiliation: Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland. engilbs@lsh.is.|Landspitali University Hospital, Mental Health Services, Hringbraut, 101, Reykjavik, Iceland. engilbs@lsh.is.
authors.forename: Engilbert
authors.initials: E
authors.lastname: Sigurdsson
mesh_terms: D000328:Adult; D000380:Agranulocytosis / Q000139:chemically induced; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D018450:Disease Progression; D057286:Electronic Health Records; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007055:Iceland; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000175:diagnosis; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Agranulocytosis; Antipsychotics; Clozapine; Neutropenia; Schizophrenia