The influence of clozapine treatment on plasma granulocyte colony-stimulating (G-CSF) levels.
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.
Pollmächer
T
T
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Fenzel
T
T
Mullington
J
J
Hinze-Selch
D
D
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D003024:Clozapine / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008137:Longitudinal Studies; D008297:Male; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
D014150:Antipsychotic Agents; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor; D003024:Clozapine