The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review

TY - JOUR

T1 - The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge

T2 - A Systematic Review

AU - Lally, John

AU - Malik, Steffi

AU - Krivoy, Amir

AU - Whiskey, Eromona

AU - Taylor, David M.

AU - Gaughran, Fiona P.

AU - Flanagan, Robert J.

AU - Mijovic, Aleksandar

AU - Maccabe, James H.

PY - 2017/10/1

Y1 - 2017/10/1

N2 - PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities, with neutropenia and agranulocytosis of most concern. Granulocyte colony-stimulating factor (G-CSF) has been used to support clozapine rechallenge after neutropenia with the aim of maintaining the neutrophil count. This study aims to explore the practice, use, safety, and efficacy of G-CSF in this context.METHODS/PROCEDURES: We conducted a systematic review to identify all studies investigating or describing G-CSF as a prophylaxis to enable continued clozapine treatment during a rechallenge.FINDINGS/RESULTS: We identified 32 reports of patients who received G-CSF either regularly (n = 23) or as required (n = 9) to support clozapine rechallenge after an episode of neutropenia necessitating discontinuation of clozapine. Seventy-five percent (n = 24) of published cases remained on clozapine with the use of continual prophylactic G-CSF or after single G-CSF administrations (n = 8). Seventy percent (n = 16) of patients in receipt of continual prophylactic G-CSF were successfully maintained on clozapine. However, 1 of the 3 episodes of rechallenge in those with a history of severe agranulocytosis (absolute neutrophil count <0.1 × 10/L) had a recurrence of agranulocytosis at week 9.IMPLICATIONS/CONCLUSIONS: Our findings suggest that G-CSF can sometimes be safely used to support the maintenance of normal neutrophil counts and clozapine use after neutropenia. Publication bias is an important limitation, however. Also, few reports clearly documented the presence or absence of an independent nonclozapine cause of the index neutropenia, which may have increased success rates. Furthermore, adverse events were not systematically recorded. Prospective studies are needed to determine safety because if agranulocytosis occurs on clozapine while supported by G-CSF, there is no obvious alternate rescue therapy to promote granulopoiesis. From the available data, it is not possible to recommend this course of action for someone with a true clozapine agranulocytosis.

AB - PURPOSE/BACKGROUND: Clozapine is associated with hematological abnormalities, with neutropenia and agranulocytosis of most concern. Granulocyte colony-stimulating factor (G-CSF) has been used to support clozapine rechallenge after neutropenia with the aim of maintaining the neutrophil count. This study aims to explore the practice, use, safety, and efficacy of G-CSF in this context.METHODS/PROCEDURES: We conducted a systematic review to identify all studies investigating or describing G-CSF as a prophylaxis to enable continued clozapine treatment during a rechallenge.FINDINGS/RESULTS: We identified 32 reports of patients who received G-CSF either regularly (n = 23) or as required (n = 9) to support clozapine rechallenge after an episode of neutropenia necessitating discontinuation of clozapine. Seventy-five percent (n = 24) of published cases remained on clozapine with the use of continual prophylactic G-CSF or after single G-CSF administrations (n = 8). Seventy percent (n = 16) of patients in receipt of continual prophylactic G-CSF were successfully maintained on clozapine. However, 1 of the 3 episodes of rechallenge in those with a history of severe agranulocytosis (absolute neutrophil count <0.1 × 10/L) had a recurrence of agranulocytosis at week 9.IMPLICATIONS/CONCLUSIONS: Our findings suggest that G-CSF can sometimes be safely used to support the maintenance of normal neutrophil counts and clozapine use after neutropenia. Publication bias is an important limitation, however. Also, few reports clearly documented the presence or absence of an independent nonclozapine cause of the index neutropenia, which may have increased success rates. Furthermore, adverse events were not systematically recorded. Prospective studies are needed to determine safety because if agranulocytosis occurs on clozapine while supported by G-CSF, there is no obvious alternate rescue therapy to promote granulopoiesis. From the available data, it is not possible to recommend this course of action for someone with a true clozapine agranulocytosis.

KW - agranulocytosis

KW - clozapine

KW - G-CSF

KW - GM-CSF

KW - granulocyte colony-stimulating factors

KW - neutropenia

KW - schizophrenia

KW - treatment-resistant

UR - http://www.scopus.com/inward/record.url?scp=85032450090&partnerID=8YFLogxK

U2 - 10.1097/JCP.0000000000000767

DO - 10.1097/JCP.0000000000000767

M3 - Review article

C2 - 28817489

SN - 0271-0749

VL - 37

SP - 600

EP - 604

JO - Journal of Clinical Psychopharmacology

JF - Journal of Clinical Psychopharmacology

IS - 5

ER -