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An alternative to interruption of treatment in recurrent clozapine-induced severe neutropenia

Departement universitaire de psychiatrie adulte, CH-1008 Prilly-Lausanne, Switzerland

EDITED BY MATTHEW HOTOPF

Declaration of interest

None with respect to Novartis (manufacturers of clozapine). P.B. is on the advisory boards of Pfizer and Eli Lilly, and has received grants from Pfizer, Lundbeck, AstraZeneca and Aventis, who have interests in the manufacture of antipsychotics.

The use of clozapine is limited by the potential for haematological adverse effects (Young et al, 1998). Facing the occurrence of neutropenia the generally accepted attitude is to interrupt the treatment, and rechallenge with clozapine is usually avoided. We report the case of a woman with schizophrenia who was re-challenged with clozapine 10 years after she had developed severe neutropenia under clozapine, and who has been kept on this medication despite the occurrence of three episodes of severe neutropenia by using granulocyte and macrophage colony stimulating factor (GM-CSF) repeatedly.

Miss M. was first admitted in 1988 for an acute psychotic episode. After failing to respond to two standard neuroleptics she was started on clozapine. Her clinical situation improved markedly. The treatment was interrupted after 6 weeks when she developed severe neutropenia. Despite various treatments she continued to hallucinate and be delusional over the next 10 years. In 1998 she was admitted because of the aggravation of her clinical state. During her 8-month hospital stay, olanzapine and sertindole, alone and combined with benzodiazepines, antidepressants and mood stabilisers, were tried without improvement. Clozapine was reintroduced. The clinical situation improved markedly and the patient left the hospital 3 weeks later. She eventually went through three episodes of severe neutropenia at weeks 10, 35 and 48, that were all successfully treated with one subcutaneous injection of GM-CSF. The clozapine dose had been gradually increased up to 450 mg/day by week 40.

The use of colony stimulating factors has been reported as a means to continue treatment despite the occurrence of severe neutropenia. However, in the case described the cytokines had to be administered only once and the dosage of clozapine was relatively low (Sperner-Unterweger et al, 1998). In the present situation, the treatment was continued despite three successive episodes of severe neutropenia and the dosage of clozapine being increased up to 450 mg/day. Even if this strategy should remain exceptional, it offers an alternative to the interruption of treatment with clozapine in some of the most severe cases.

REFERENCES

Sperner-Unterweger, B., Czeipek, I., Gaggl, S., et al (1998) Treatment of severe clozapine-induced neutropenia with granulocyte colony-stimulating factor (G-CSF). Remission despite continuous treatment with clozapine. British Journal of Psychiatry, 172, 82-84.[Abstract/Free Full Text]

Young, C. R., Bowers, M. B. & Mazure, C. M. (1998) Management of the adverse effects of clozapine. Schizophrenia Bulletin, 24, 381-390.

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Conus, P. Articles by Baumann, P. Search for Related Content PubMed Articles by Conus, P. Articles by Baumann, P.