Filgrastim May Provide an Alternative to Discontinuing Clozapine Therapy

For patients with treatment-resistant schizophrenia, clozapine is a key antipsychotic. However, because clozapine is associated with hematological abnormalities, including neutropenia and leukopenia, patients must sometimes discontinue treatment. Sudden withdrawal of clozapine is linked with serious outcomes, however, including an increased risk of suicide.

The risk evaluation and mitigation strategy program for clozapine allows for patients to receive clozapine—even in the setting of moderate to severe neutropenia—if the benefit to psychiatric treatment outweighs the risk of recurrent neutropenia. However, literature that can guide appropriate treatment for such patients is limited.

A recently published case report suggests that using filgrastim to control leukopenia and neutropenia could allow patients to continue to receive clozapine without interruption. Published in The Mental Health Clinician, the report describes a 55-year-old male patient with chronic paranoid schizophrenia.

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The patient had achieved significant clinical improvement with clozapine treatment, and he attained functional independence without hospitalization. He was able to receive 20 years of clozapine therapy before he developed leukopenia, after which clozapine was withdrawn, precipitating a rapid worsening of his schizophrenia symptoms. Over the following 2 years, the patient tried, and had an inadequate response to, 7 other medications.

Because the patient’s symptoms were worsening, a retrial of clozapine was deemed necessary. However, 2 months after discharge from the hospital following psychiatric improvement with clozapine therapy, moderate leukopenia and mild neutropenia recurred, and his clozapine was once again held.

The patient was then treated with 5 daily doses of subcutaneous filgrastim (300 mcg/mL), and his white blood cells and absolute neutrophil count recovered within 4 days, allowing him to restart his clozapine. An interdisciplinary team determined that the patient could receive uninterrupted clozapine therapy with filgrastim as needed.

The patient had 1 period of leukopenia and neutropenia that necessitated interruption of clozapine, and his filgrastim was eventually replaced with a different colony-stimulating factor therapy (sargramostim) because of a formulary change, but over the past 3 years of receiving neutropenia treatment, his schizophrenia symptoms have been well controlled, and his clozapine use has been uninterrupted. The patient continues to have his white blood cells and absolute neutrophil count monitored weekly.

The authors of the case report conclude that filgrastim or sargramostim provide a potential alternative to clozapine discontinuation in the case of neutropenia for patients who have been clinically stable on their therapy.

Reference

Kars A, Lister J. Utilization of G-CSF and GM-CSF as an alternative to discontinuation in clozapine-induced neutropenia or leukopenia: a case report and discussion. Ment Health Clin. 2018;8(5):250-255. doi: 10.9740/mhc.2018.09.250.