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Experience of maintaining clozapine medication in patients with ‘red-alert zone’ neutropenia: long-term follow-up results

Ahn, Yong Mina; Jeong, Seong Hoonb; Jang, Hong Suka; Koo, Young Jinc; Kang, Ung Gua; Lee, Kyu Younga; Kim, Yong Sika

International Clinical Psychopharmacology: March 2004 - Volume 19 - Issue 2 - p 97-101
Original Articles

According to the recommended guidelines by Novartis, neutropenia in the range of a white blood cell count less than 3000 per mm3, or an absolute neutrophil count (ANC) less than 1500 per mm3, is classified as being in the ‘red-alert zone’ during clozapine treatment. If a patient's blood test result falls into this zone, immediate discontinuation of clozapine is recommended, and reinstitution is prohibited. However, in some patients, it is not entirely feasible to implement this standard guideline because of the lack of effective alternatives to clozapine treatment. Through retrospective chart reviews, five patients who had been maintained on clozapine treatment despite red-alert zone neutropenia were selected. The haematological and clinical courses of these patients were followed for more than 600 days and were compared with those of two control patients who discontinued clozapine due to neutropenia. In all five patients, no additional episodes of neutropenia occurred during the observation period despite continued clozapine treatment. However, three of them maintained a lower neutrophil count for the remaining observation period. Four patients responded favourably to clozapine treatment as judged by Clinical Global Impression score. Given the limitations of a retrospective chart review and the small number of patients, we cannot draw any definite conclusions. However, while the guidelines for the prevention of agranulocytosis should be generally followed, it may be that judicious continuation of clozapine treatment is less risk-prone than previously considered in selected cases where only a few feasible alternatives to clozapine are available. Moreover, there is an apparent necessity to develop new measures or methods that can differentiate between benign neutropenia and that leading to fatal agranulocytosis.

aDepartment of Psychiatry, Seoul National University College of Medicine, Seoul

bChook-Ryoung Evangelical Hospital, Kyunggi-Do

cDepartment of Psychiatry, Pundang Jesaeng General Hospital, Seongnam-Si, South Korea

Correspondence and requests for reprints to Yong Sik Kim, Department of Psychiatry, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110–799, South Korea

Tel: +82 2 7602204; fax: +82 2 7447241;


Received 7 August 2003 Accepted 6 November 2003

© 2004 Lippincott Williams & Wilkins, Inc.