THE INFLUENCE OF CLOZAPINE TREATMENT ON PLASMA GRANULOCYTE-COLONY-STIMULATING (G-CSF) LEVELS

The antipsychotic drug clozapine frequently induces transient increase s in white blood cell counts that have been found to be sensitive, but non-specific, predictors of subsequent life-threatening agranulocytos is. Granulocyte colony-stimulating factor (G-CSF) is an endogenous hem atopoietic growth factor that plays a pivotal role in granulopoiesis. In addition, G-CSF has successfully been used to treat clozapine-induc ed agranulocytosis. We performed a longitudinal investigation of the p lasma levels of G-CSF in 20 schizophrenic patients during six weeks of clozapine treatment. Clozapine transiently increased plasma G-CSF lev els 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 a ccompanied by increased granulocyte and monocyte counts, increased rec tal temperature and increased plasma levels of other cytokines and cyt okine 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 hypot hesize that a persistent increase along with a decline in white cell c ounts following an early spike during clozapine treatment might predic t the occurrence of agranulocytosis.