The influence of clozapine treatment on plasma granulocyte colony-stimulating (G-CSF) levels

Pharmacopsychiatry. 1997 Jul;30(4):118-21. doi: 10.1055/s-2007-979495.


The antipsychotic drug clozapine frequently induces transient increases in white blood cell counts that have been found to be sensitive, but non-specific, predictors of subsequent life-threatening agranulocytosis. Granulocyte colony-stimulating factor (G-CSF) is an endogenous hematopoietic growth factor that plays a pivotal role in granulopoiesis. In addition, G-CSF has successfully been used to treat clozapine-induced agranulocytosis. We performed a longitudinal investigation of the plasma levels of G-CSF in 20 schizophrenic patients during six weeks of clozapine treatment. Clozapine transiently increased plasma G-CSF levels in 55% of the subjects studied. This effect was most prominent at the end of the second week of treatment. Increased G-CSF levels were accompanied by increased granulocyte and monocyte counts, increased rectal temperature and increased plasma levels of other cytokines and cytokine receptors. The results presented suggest that G-CSF is involved in clozapine-induced increases in granulocyte counts seen early during treatment. Like granulocytosis, granulocytopenia is known to occur in conjunction with increased systemic G-CSF levels. Therefore, we hypothesize that a persistent increase along with a decline in white cell counts following an early spike during clozapine treatment might predict the occurrence of agranulocytosis.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Body Temperature / drug effects
  • Clozapine / therapeutic use*
  • Cytokines / blood
  • Granulocyte Colony-Stimulating Factor / blood*
  • Humans
  • Leukocyte Count / drug effects
  • Longitudinal Studies
  • Male
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy


  • Antipsychotic Agents
  • Cytokines
  • Granulocyte Colony-Stimulating Factor
  • Clozapine