title: Circadian rhythm of neutrophil counts and granulocyte macrophage-colony stimulating factor (GM-CSF) under clozapine treatment: a case report.
abstract: Agranulocytosis is a severe side effect of clozapine which requires stopping this medication immediately in the case of progressive neutropenia. There are, however, cases of benign neutropenia under clozapine that do not progress. The ability to predict progression vs. non-progression in neutropenia cases under clozapine would be highly valuable for avoiding unnecessary treatment withdrawals. In this context, we closely monitored circadian neutrophil counts and granulocyte macrophage-colony stimulating factor (GM-CSF) levels in a patient who had low normal neutrophil counts at baseline and developed neutropenia under clozapine treatment.
  
  
  METHODS
  Venous blood samples were drawn in close intervals for 4 weeks. At several time points blood was sampled in the morning between 08:30 and 9:30 h and a second time in the afternoon between 14:00 and 15:00 h.
  
  
  RESULTS
  The circadian rhythm of neutrophil counts and GM-CSF levels was unchanged. There was no progression to agranulocytosis, and clozapine could be continued.
  
  
  CONCLUSIONS
  In view of the available literature and the presented case it is suggested that further studying of circadian profiles of neutrophil counts, neutrophil regulatory factors, such as GM-CSF, and their intercorrelation may help to find a biomarker of benign vs. malign neutropenia under clozapine.
authors.affiliation: Department of Psychiatry and Psychotherapy, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrea
authors.forename: Karin
authors.initials: K
authors.lastname: Fehsel
authors.forename: Joachim
authors.initials: J
authors.lastname: Cordes
authors.forename: Christian
authors.initials: C
authors.lastname: Luckhaus
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D002940:Circadian Rhythm / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003024:Clozapine