Clozapine rechallenge following neutropenia using granulocyte colony-stimulating factor: A Quebec case series. (September 2021)

• Record Type: Journal Article
• Authors: Béchard, Laurent; Corbeil, Olivier; Plante, Maude; Thivierge, Marc-André; Lafrenière, Charles-Émile; Roy, Marc-André; Demers, Marie-France
• Is Part Of: Journal of psychopharmacology. Volume 35:Number 9(2021)
• Page Start: 1152
• Page End: 1157
• Publication Date: 2021-09
• Subjects: Clozapine -- clozapine-induced agranulocytosis -- clozapine-induced neutropenia -- granulocyte colony-stimulating factor -- rechallenge -- schizophrenia; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/02698811211029737
• Languages: English
• ISSNs: 0269-8811

Abstract

Background: Clozapine has a unique efficacy profile among individuals suffering from treatment-resistant schizophrenia, but is associated with hematological side effects. The use of granulocyte colony-stimulating factors (G-CSF) to allow clozapine continuation or rechallenge has emerged as a promising option, but evidence is still scarce. Aim: To describe the largest case series so far published regarding this practice. Method: A national clozapine hematological monitoring database was consulted to identify all patients who had had neutrophil count <1.5 × 10 9 /L since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who had received at least one dose of G-CSF, such as filgrastim, while being exposed to clozapine. All data were collected retrospectively, using patients' medical files, from January to July 2019. Results: Using G-CSF, three out of eight patients could maintain clozapine despite neutropenia episodes that otherwise would have required treatment discontinuation. The only side effect reported was mild short-lived back pain, over a mean 3-year follow-up period. In all but one case, filgrastim was used on an "as-needed" basis at doses of 300 mcg administered subcutaneously. Conclusion: These results suggest that the "as-needed" use of G-CSF is well-tolerated and may allow clozapine rechallenge in some well-selected patients, adding to the paucity of data regarding long-term safety and efficacy of this strategy. More research may help to better define potential candidates and optimal regimen of such practice.