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Failure of Filgrastim to Prevent Severe Clozapine-Induced Agranulocytosis

Tricia G. Majczenko, MD, Jonathan T. Stewart, MD
Volume: 101 Issue: 6 June, 2008

Abstract:

Although a highly effective medication, the usage of clozapine is limited mostly by its 2.7% incidence of neutropenia. It is often a treatment of last resort for patients with severe psychiatric illnesses, and therefore often the only medication to which a patient has responded. There has thus been a great deal of interest in ways to continue the medication in spite of emergent blood dyscrasias. There have been several reports documenting the successful continuation of clozapine in spite of neutropenia by adding granulocyte colony-stimulating factors such as filgrastim. This strategy was unsuccessful for a 63-year-old man, resulting in severe, prolonged agranulocytosis. Although a promising strategy for such refractory patients, its inherent dangers should not be underestimated.


Key Points


* Clozapine is a highly effective medication for severe psychiatric illness, but its use is limited by its 2.7% incidence of neutropenia.


* There have been several reports of continuing clozapine in otherwise refractory patients who develop neutropenia by adding granulocyte colony-stimulating factors such as filgrastim.


* Although the combination of clozapine and filgrastim is a promising treatment option, its dangers should not be underestimated.

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References:

1. Munro J, O’Sullivan D, Andrews C, et al. Active monitoring of 12,760 clozapine recipients in the UK and Ireland: beyond pharmacovigilance. Br J Psychiatry 1999;175:576–580.
 
2. Sperner-Unterweger B, Czeipek I, Gaggl S, et al. Treatment of severe clozapine-induced neutropenia with granulocyte colony-stimulating factor (G-CSF): remission despite continuous treatment with clozapine. Br J Psychiatry 1998;172:82–84.
 
3. Hagg S, Rosenius S, Spigset O. Long-term combination treatment with clozapine and filgrastim in patients with clozapine-induced agranulocytosis. Int Clin Psychopharmacol 2003;18:173–174.
 
4. Conus P, Nanzer N, Baumann P. An alternative to interruption of treatment in recurrent clozapine-induced severe neutropenia. Br J Psychiatry 2001;179:180.
 
5. Rajagopal G, Graham JG, Haut FFA. Prevention of clozapine-induced granulocytopenia/agranulocytosis with granulocyte-colony stimulating factor (G-CSF) in an intellectually disabled patient with schizophrenia. J Intellect Disabil Res 2007;51:82–85.
 
6. Dunk LR, Annan LJ, Andrews CD. Rechallenge with clozapine following leucopenia or neutropenia during previous therapy. Br J Psychiatry 2006;188:255–263.

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