Clozapine-Associated Agranulocytosis Treatment With Granulocyte Colony-Stimulating Factor/Granulocyte-Macrophage Colony-Stimulating Factor: A Systematic Review

Purpose/Background Clozapine is associated with hematological abnormalities, notably neutropenia, which may progress to agranulocytosis. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used to reduce the frequency and duration of clozapine-associated neutropenia. This review aims to explore the use, efficacy, and tolerability of these cytokines in the treatment of clozapine-associated agranulocytosis. Methods/Procedures We conducted a systematic review of published interventional and observational studies, case series, and case reports where G-CSF/GM-CSF was used to treat clozapine-associated agranulocytosis. Findings/Results We identified 29 reports (40 patients). The median duration of neutrophil recovery time after stopping clozapine and starting cytokine treatment was 7 days (range, 2-13 days) for those with agranulocytosis (absolute neutrophil count < 0.5 x 10(9) cells/L). Ninety-four percent (n = 29) had no serious adverse reactions, and no deaths occurred. Implications/Conclusions Our findings indicate that G-CSF/GM-CSF use is well tolerated and suggest that G-CSF can sometimes be safely used to reduce the duration of neutropenia associated with clozapine use. However, the interpretation of this outcome is difficult, given the likely publication bias for positive outcomes in case reports.