Trial of prophylactic GCSF (white cell growth factor) use to prevent low white cell counts in people re-exposed to clozapine

Background: clozapine is the most effect antipsychotic drug for treatment-refractory schizophrenia. Approximately 3.8% of people prescribed clozapine develop neutropenia which necessitates discontinuation of drug. Cessation of clozapine often results in psychotic rebound symptoms and may deny highly disabled patients the only effective means of psychotic symptom control. Despite this clozapine rechallenge is rarely undertaken due to concerns about the morbidity of recurrent neutropenia and lack of evidence based rechallenge strategies. One option for clozapine rechallenge is the concomitant use of prophylactic granulocyte-colony stimulating factor (G-CSF) to prevent recurrent neutropenia. However, there is limited current literature reporting the safety and efficacy of such an approach. A recent review identified 23 cases of clozapine rechallenge using prophylactic G-CSF in people previously experiencing clozapine associated neutropenia. This review reported a success rate of 70% at follow-up of one year with a favourable safety profile. However, the protocol for rechallenge was not standardised across cases, analysis was retrospective in most cases and there was risk of reporting bias given most data were derived from case series or single case reports. Further prospective evaluation of prophylactic G-CSF use for clozapine rechallenge in people previously experiencing clozapine associated neutropenia would be beneficial to determine the safety and efficacy of such an approach. Principals and rationale of therapeutic strategy: G-CSF has an established evidence base for the prevention of chemotherapy induced neutropenia and is also effective at augmenting neutrophil counts in people with congenital neutropenic syndromes and immunologically mediated neutropenia. Furthermore, G-CSF is beneficial in reducing the duration of clozapine-associated neutropenia following drug cessation. In people previously experiencing clozapine-associated neutropenia who are re-exposed to clozapine, G-CSF could plausibly augment neutrophil counts to prevent recurrent neutropenia. Hypothesis: use of regular G-CSF can be used safely in people previously experiencing clozapine-associated neutropenia during re-initiation of clozapine to prevent recurrent neutropenia and facilitate ongoing use of clozapine.