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

  title={The Use of Granulocyte Colony-Stimulating Factor in Clozapine Rechallenge: A Systematic Review},
  author={John Lally and Steffi Malik and Amir Krivoy and Eromona Whiskey and David Taylor and Fiona Gaughran and R. J. Flanagan and Aleksandar Mijovic and James Hunter MacCabe},
  journal={Journal of Clinical Psychopharmacology},
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… 


The use of G-CSF to maintain clozapine despite neutropenia or agranulocytosis in treatment resistant schizophrenia patients in Quebec province, Canada is described, which is the largest case series of clozAPine rechallenge using G- CSF and adds to the 39 already described cases.

Clozapine rechallenge following neutropenia using granulocyte colony-stimulating factor: A Quebec case series

The 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.

Utilization of G-CSF and GM-CSF as an alternative to discontinuation in clozapine-induced neutropenia or leukopenia: A case report and discussion

A case report of successful periodic granulocyte-macrophage colony-stimulating factor use with clozapine in a patient with treatment-resistant schizophrenia is presented, as well as discussion of a practical approach to patients with possible clozAPine-induced neutropenia or leukopenia.

Re-titration rates after clozapine-induced neutropenia or agranulocytosis: A case report and literature review.

This case presentation presents a case of a 50-year-old Caucasian female with a history of schizoaffective disorder who was successfully rechallenged on clozapine one month after developing clozAPine-induced neutropenia and encourages researchers to publish their dosing schedule in detail after an episode of neutropania or agranulocytosis.

Extended Requirement of Granulocyte Colony-Stimulating Factor for Clozapine-Associated Neutropenia.

The patient attempted suicide by trying to drown himself in a river while wearing a backpack filled with stones, and he suffered no injuries and only mild hypothermia, and the medication was continued with 450 mg/d clozapine but monitored medication intake evenmore precisely.

Clozapine-induced agranulocytosis

A review of the epidemiology of clozapine-induced agranulocytosis (CLIA), advances in identifying genetic risk factors, and the preventive measures to reduce the risk of CLIA is presented.

Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital

Even in this extreme group of patients with treatment resistant schizophrenia, clozapine can be safely and effectively re/initiated following neutropenias, resulting in marked benefits for patients, according to a case series of 14 consecutive patients rechallenged in a high-secure psychiatric hospital.

Clozapine Re-Challenge and Initiation Despite Neutropenia and Outcomes from 14 Patients

With careful planning and monitoring, clozapine can be successfully reinitiated following CIN or in the face of preexisting neutropenia resulting in significant benefits for patients.

G-CSF mediated neutrophil augmentation in a unique case of comorbid idiopathic Parkinson’s disease and treatment-resistant schizophrenia on clozapine

It is suggested that G-CSF might be considered as a treatment option in other cases where clozapine-associated neutropenia obstructs its use, and a unique case of a patient who developed early-onset PD on a background of antecedent treatment-resistant schizophrenia is presented.

Continuation of Treatment With Clozapine After an Episode of Neutropenia

A risk-benefit approach supports continuing clozapine treatment after an episode of neutropenia and recommends modifying clozAPine treatment protocol absolute neutrophil count thresholds to less than 1000/μL to determine treatment cessation.



Granulocyte Colony Stimulating Factor (G-CSF) can allow treatment with clozapine in a patient with severe Benign Ethnic Neutropaenia (BEN): a case report

It is shown that response to granulocyte colony stimulating factor (G-CSF) may be quite variable and difficult to predict, but with careful monitoring it can be used to increase the ANC count and allow continued treatment with clozapine.

G-CSF Dosing to Prevent Recurrent Clozapine-Induced Agranulocytosis.

The 5.4-year course of a 19-year-old Caucasian malewith schizoaffective disorder whoveloped agranulocytosis on three consecutive clozapine trials, but who thereafter achieved long-term stabilization of psychiatric symptoms and absolute neutrophil count (ANC) through concurrentuse of clozAPine andgranulocyte colony-stimulating factor (G-CSF) with clear dosing parameters is reported.

Treatment of severe clozapine-induced neutropenia with granulocyte colony-stimulating factor (G-CSF)

This case report is not intended to challenge the clinical practice of discontinuing clozapine upon the development of neutropenia/agranulocytosis, but to stimulate further research in the pathophysiology and clinical consequences of a clozAPine rechallenge after a WBC decline.

Successful Use of Single Doses of Granulocyte-Colony Stimulating Factor (G-CSF) in the Treatment of Late-Onset Agranulocytosis Associated With Clozapine in a Patient With Treatment-Resistant Schizophrenia: A Case Report.

A patient with long-term schizophrenia who developed a late-onset clozapinerelated agranulocytosis on 2 occasions is reported on.

Optimizing outcomes in clozapine rechallenge following neutropenia: a cohort analysis.

In this selected population, the initial neutropenia was unlikely to be related to clozapine in a substantial proportion of cases, and this group was successfully rechallenged following careful consideration of the risks and benefits.

Prevention of clozapine-induced granulocytopenia/agranulocytosis with granulocyte-colony stimulating factor (G-CSF) in an intellectually disabled patient with schizophrenia.

Treatment with granulocyte-colony stimulating factor prevented discontinuation of clozapine, enabling an intellectually disabled patient's recovery from a schizophrenic illness.

Clozapine Treatment in a Patient with a Persistently Low Neutrophil Count

The guidelines for hematologic monitoring may prevent some patients from access to this clozapine treatment in a Patient with a Persistently Low Neutrophil Count, but not all neutropenic patients will progress to agranulocytosis.

Rechallenge with clozapine following leucopenia or neutropenia during previous therapy

No clear risk factor for repeat blood dyscrasias was identified and after risks and benefits have been considered, rechallenge may well be justified in some patients.

A case report of clozapine augmentation with granulocyte colony stimulating factor (G-CSF)

It was possible to continue treatment with clozapine to good effect by using granulocyte colony stimulating factor (G-CSF) as an adjunct by using the decision-making process and the clinical evidence behind this approach.