Circadian rhythm of neutrophil counts and granulocyte macrophage-colony stimulating factor (GM-CSF) under clozapine treatment: A case report

Abstract

In view of the available literature and the presented case it is suggested that further studying of circadian profiles of neutrophil counts, neutrophil regulatory factors, such as GM-CSF, and their intercorrelation may help to find a biomarker of benign vs. malign neutropenia under clozapine.

Morning granulocytopenia in two patients with connective-tissue disease treated with oral corticosteroids

“…Since that time, only seven cases have been reported. Four of these cases were associated with clozapine,4–7 one with risperidone,8 one with methimazole,9 and one with PSL treatment10 (table 1). Because morning granulocytopenia is asymptomatic and does not systematically predispose the person to an increased risk of serious infection,11 12 effective treatments for other conditions may not need to be stopped or changed.…”

“…The results of several studies indicate that the diurnal change in levels of serum G-CSF, granulocyte macrophage-colony stimulating factor (GM-CSF) or cortisol is related to morning pseudoneutropenia 8 9. In contrast, other reports suggest that morning pseudoneutropenia does not affect the normal circadian rhythm of G-CSF, GM-CSF and cortisol levels, and there is sufficient compensatory stimulation of granulopoiesis and preservation of the diurnal variation in circulating neutrophils 5 7. Although the relationship between morning granulocytopenia and cortisol, G-CSF and GM-CSF is still unclear, these reports indicate that the diurnal change in neutrophil levels in normal people versus those affected by morning granulocytopenia are qualitatively different.…”

Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

“…c. Low pre-treatment neutrophil counts with or without BEN: optimise blood sampling. Changing sampling time from morning to afternoon (ideally after exercise) may be sufficient to allow initiation and on-going treatment [44][45][46][47]. Longer-term processes are necessary to ensure this continues.…”