The British Journal of Psychiatry (2006) 189: 186. doi: 10.1192/bjp.189.2.186
© 2006 The Royal College of Psychiatrists
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Correspondence

Clozapine treatment following blood dyscrasia

D. Esposito

Department of Psychiatry, Bicêtre, Assistance Publique - Hôpitaux de Paris, Paris XI University, INSERM U 669, 8 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cédex, France. Email: david.esposito{at}club-internet.fr

P. Hardy and E. Corruble

Department of Psychiatry, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France

EDITED BY KIRIAKOS XENITIDIS and COLIN CAMPBELL

Dunk et al (2006) investigated 53 patients who were rechallenged with clozapine following leucopenia or neutropenia during previous therapy and found that 33 did not experience a second episode of blood dyscrasia and were able to continue drug treatment. This result is of considerable clinical relevance because it suggests that some patients with leucopenia or neutropenia may unnecessarily be denied effective clozapine treatment.

We agree that there may be two types of clozapine-associated neutropenia: an early sign of incipient agranulocytosis and a more common transient and harmless phenomenon, not necessitating the discontinuation of drug treatment. Transient neutropenia (defined as a return of the neutrophil count to normal values without changing the clozapine dosage) was found in 22% of 68 patients treated with clozapine for the first time (Hummer et al, 1994). Neutropenia of short duration (2-5 days) and weekly benign variations of the neutrophil count have been reported. Marked circadian variations in the number of circulating neutrophils (morning pseudoneutropenia) have also been described in several clozapine-treated patients (Ahokas & Elonen, 1999; Esposito et al, 2004).

The actual issue might therefore not be which patients could be rechallenged with clozapine following drug-associated neutropenia but which could be maintained on clozapine despite this side-effect. Laboratory screening tests, including the use of a hydrocortisone test, are being devised to determine whether clozapine-associated neutropenia is transient or malignant (Murry & Laurent, 2001). Until these tests become available for routine use, it is necessary to increase the frequency with which white blood cell counts are determined. As first suggested by Ahokas & Elonen (1999), when the absolute neutrophil count is below the normal range in the morning, the test should be repeated in the afternoon of the same day before a decision to stop clozapine treatment is made. This might be the basis for further clarification of the significance of transient neutropenia.

REFERENCES

  1. Ahokas, A. & Elonen, E. (1999) Circadian rhythm of white blood cells during clozapine treatment. Psychopharmacology, 144, 301 -302.[CrossRef][Medline]
  2. Dunk, L. R., Annan, L. J. & Andrews, C. D. (2006) Rechallenge with clozapine following leucopenia or neutropenia during previous therapy. British Journal of Psychiatry, 188, 255 -263.[Abstract/Free Full Text]
  3. Esposito, D., Aouille, J., Rouillon, F., et al (2004) Two-year follow-up of a patient with successful continuation of clozapine treatment despite morning pseudoneutropenia. Journal of Clinical Psychiatry, 65, 1281.
  4. Hummer, M., Kurz, M., Barnas, C., et al (1994) Clozapine-induced transient white blood count disorders. Journal of Clinical Psychiatry, 55, 429 -432.
  5. Murry, P. & Laurent, A. (2001) Is it possible to distinguish between benign and malignant neutropenia in clozapine-treated patients by means of a hydrocortisone test? Psychopharmacology, 158, 329 -330.[CrossRef][Medline]



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