CLOZAPINE-INDUCED AGRANULOCYTOSIS - INCIDENCE AND RISK-FACTORS IN THE UNITED-STATES
CLOZAPINE-INDUCED AGRANULOCYTOSIS - INCIDENCE AND RISK-FACTORS IN THE UNITED-STATES
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DOI：
10.1056/nejm199307153290303
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发表时间：
1993-07-15
影响因子：
158.5
通讯作者：
SCHAAF, JA
中科院分区：
文献类型：
--
作者：
ALVIR, JMJ;LIEBERMAN, JA;SCHAAF, JA
背景氯氮平是一种非典型的抗精神病药物，在治疗难治性精神分裂症患者时比标准的抗精神病药物更有效。与传统的精神抑制剂不同，氯氮平与急性锥体外系症状或迟发性运动障碍的发生无关。限制其使用的主要因素是潜在的致命性粒细胞缺乏症的风险，估计发生在1%至2%的治疗患者中。在氯氮平被美国食品和药物管理局批准后，它于1990年2月在美国上市，只是作为一个特殊的监督系统（Clozaril患者管理系统，或CPMS）的一部分，在该系统中，患者需要每周进行白细胞计数以获得药物供应。我们通过生存分析评估了1990年2月至1991年4月的CPMS数据，以确定粒细胞缺乏症的发生率以及年龄和性别等潜在危险因素的影响。研究数据来自11,555名在氯氮平上市后接受治疗的患者。73例患者发生粒细胞缺乏症，2例患者死于感染并发症。61例患者在开始治疗后3个月内发生粒细胞缺乏症。这种副作用的累积发生率在1年时为0.80%（95%置信区间，0.61至0.99），在1年半时为0.91%（95%置信区间，0.62至1.20）。粒细胞缺乏症的风险随着年龄的增长而增加，女性的风险更高。粒细胞缺乏症的发生是氯氮平给药的实质性危害，但通过监测白细胞计数可以降低这种危害。粒细胞缺乏症的风险随着年龄的增长而增加，治疗前6个月后发生率降低，这为将来氯氮平治疗的处方和监测提供了额外的指南。
Background. Clozapine is an atypical antipsychotic agent that is more effective than standard neuroleptic drugs in the treatment of patients with refractory schizophrenia. Unlike classic neuroleptic agents, clozapine is not associated with the development of acute extrapyramidal symptoms or tardive dyskinesia. The main factor limiting its use is the risk of potentially fatal agranulocytosis, estimated to occur in 1 to 2 percent of treated patients. After clozapine was approved by the Food and Drug Administration, it became available for marketing in the United States in February 1990 only as part of a special surveillance system (the Clozaril Patient Management System, or CPMS), in which a weekly white-cell count was required for the patient to receive a supply of the drug.Methods. We evaluated the CPMS data for February 1990 through April 1991 by survival analysis to determine the incidence of agranulocytosis and the effects of potential risk factors such as age and sex. Data were available for 11,555 patients who received clozapine during the period after marketing began.Results. Agranulocytosis developed in 73 patients, resulting in death from infectious complications in 2 patients. Episodes of agranulocytosis occurred in 61 patients within three months after they began treatment. The cumulative incidence of this side effect was 0.80 percent (95 percent confidence interval, 0.61 to 0.99) at 1 year and 0.91 percent (95 percent confidence interval, 0.62 to 1.20) at 1 1/2 years. The risk of agranulocytosis increased with age and was higher among women.Conclusions. The occurrence of agranulocytosis is a substantial hazard of the administration of clozapine, but this hazard can be reduced by monitoring the white-cell count. The increasing risk of agranulocytosis with age and the reduced incidence after the first six months of treatment provide additional guidelines for the prescription and monitoring of clozapine treatment in the future.