Faculté de pharmacie, Université Laval, Québec, Canada.
Institut universitaire en santé mentale de Québec, Centre intégré universitaire de santé et de services sociaux de la Capitale-Nationale, Quebec, Canada.
J Psychopharmacol. 2021 Sep;35(9):1152-1157. doi: 10.1177/02698811211029737. Epub 2021 Jul 6.
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.
To describe the largest case series so far published regarding this practice.
A national clozapine hematological monitoring database was consulted to identify all patients who had had neutrophil count <1.5 × 10/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.
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.
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.
氯氮平在治疗抵抗性精神分裂症患者中具有独特的疗效,但与血液学副作用相关。使用粒细胞集落刺激因子(G-CSF)允许氯氮平继续或重新使用已成为一种有前途的选择,但证据仍然有限。
描述迄今为止发表的关于这种做法的最大病例系列。
查阅全国氯氮平血液学监测数据库,以确定自 2004 年以来魁北克省所有中性粒细胞计数<1.5×10/L 的患者,并与医院药房软件交叉引用,以确定至少接受过一次 G-CSF(如非格司亭)治疗的患者在接触氯氮平时。所有数据均使用患者的病历,从 2019 年 1 月至 7 月进行回顾性收集。
使用 G-CSF,八名患者中有三名尽管中性粒细胞减少症发作,但仍能维持氯氮平治疗,否则需要停止治疗。在平均 3 年的随访期间,报告的唯一副作用是轻度短暂背痛。除一例外,所有患者均按需使用 300μg 皮下注射的非格司亭。
这些结果表明,G-CSF 的“按需”使用耐受性良好,并且可以允许某些精选患者重新使用氯氮平,这增加了关于这种策略的长期安全性和疗效的数据有限。更多的研究可能有助于更好地确定潜在的候选者和这种实践的最佳方案。