氯氮平所致粒细胞缺乏症。美国的发病率及危险因素。

Clozapine-induced agranulocytosis. Incidence and risk factors in the United States.

作者信息

Alvir J M, Lieberman J A, Safferman A Z, Schwimmer J L, Schaaf J A

机构信息

Department of Psychiatry, Hillside Hospital, Division of Long Island Jewish Medical Center, Glen Oaks, N.Y. 11004.

出版信息

N Engl J Med. 1993 Jul 15;329(3):162-7. doi: 10.1056/NEJM199307153290303.

DOI:10.1056/NEJM199307153290303

PMID:8515788

Abstract

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.

摘要

背景

氯氮平是一种非典型抗精神病药物，在治疗难治性精神分裂症患者方面比标准抗精神病药物更有效。与经典抗精神病药物不同，氯氮平不会引发急性锥体外系症状或迟发性运动障碍。限制其使用的主要因素是存在潜在致命性粒细胞缺乏症的风险，据估计，接受治疗的患者中1%至2%会出现这种情况。氯氮平经美国食品药品监督管理局批准后，于1990年2月在美国上市，但仅作为特殊监测系统（氯氮平患者管理系统，即CPMS）的一部分，在该系统中，患者要获得药物供应需每周进行白细胞计数。

方法

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风险因素的影响。数据来自上市后接受氯氮平治疗的11,555例患者。

结果

73例患者发生了粒细胞缺乏症，其中2例因感染并发症死亡。61例患者在开始治疗后的三个月内出现粒细胞缺乏症发作。这种副作用的累积发生率在1年时为0.80%（95%置信区间为0.61至0.99），在1.5年时为0.91%（95%置信区间为0.62至1.20）。粒细胞缺乏症的风险随年龄增加而升高，女性中的发生率更高。