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

Abstract

Treatment of psychosis in Parkinson’s disease (PD) is challenging; pharmacological options are limited, with clozapine considered most effective. The risk of agranulocytosis restricts the use of clozapine, but, where this occurs, cautious re-challenge with granulocyte stimulating factor can be successful. We present a unique case of a patient who developed early-onset PD on a background of antecedent treatment-resistant schizophrenia, who had been treated effectively with clozapine for over 15 years with no adverse events. However, during a hospital admission intended to optimise her Parkinsonian medications, she developed persistent neutropenia necessitating clozapine discontinuation. Numerous attempts to re-challenge with clozapine failed until augmentation with lithium and G-CSF was trialled. Two doses of G-CSF led to a sustained increase in the neutrophil count, allowing the continuation of clozapine therapy in the 1 year of follow up. This illustrates the potential for G-CSF to be used to facilitate clozapine use in a patient population not described previously. Neutrophil augmentation allowed the sustained continuation of this effective therapy, treating her psychotic symptoms without detriment to her movement disorder. We suggest that G-CSF might be considered as a treatment option in other cases where clozapine-associated neutropenia obstructs its use.

Clozapine rechallenge or continuation despite neutropenia or agranulocytosis using colony-stimulating factor: A systematic review

“…One case was also reported in two different articles and was therefore only included once in this review ( Meyer et al, 2015 ; Spencer et al, 2012 ). As detailed in Table 1 , 27 articles were case reports or non-consecutive series (total n = 38 cases) ( Broughton et al, 2012 ; Comacchio et al, 2016 ; Conus et al, 2001 ; Elmore et al, 2016 ; Fabre-Bernal et al, 2019 ; Foster et al, 2017 ; Freeman et al, 2016 ; Friedman et al, 2017 ; Gopalakrishnan et al, 2013 ; Gugger and Caley, 2007 ; Hagg et al, 2003 ; Hazewinkel et al, 2013 ; Huguet et al, 2013 ; Joffe et al, 2009 ; Karst and Lister, 2018 ; Khan et al, 2013 ; Majczenko and Stewart, 2008 ; Martina et al, 2019 ; Mathewson and Lindenmayer, 2007 ; Morrow et al, 2020 ; O’Neill et al, 2021 ; Rajagopal et al, 2007 ; Ruiz-Doblado et al, 2020 ; Sengupta and Harvey, 2010 ; Shuman et al, 2021 ; Spencer et al, 2012 ; Sperner-Unterweger et al, 1998 ), while there were only 2 consecutive case series ( n = 15 cases) ( Béchard et al, 2021 ; Silva et al, 2021 ) and 1 retrospective cohort study ( n = 6 cases) ( Meyer et al, 2015 ), for a total of 59 individual cases.…”