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Clozapine-Associated Agranulocytosis Treatment With Granulocyte Colony-Stimulating Factor/Granulocyte-Macrophage
John Lally1, Steffi Malik, Eromona Whiskey
1From the *Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; †Department of Psychiatry, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland; ‡Medical School, University of Bristol, Bristol; §National Psychosis Service, and ∥Pharmacy Department, South London and Maudsley NHS Foundation Trust; and ¶Institute of Pharmaceutical Science, King's College London; and #Department of Haematological Medicine, King's College Hospital, London, United Kingdom.
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 × 10 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.
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