Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine.
Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine.
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DOI：
10.1001/archpsyc.1988.01800330013001
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发表时间：
1988-09
影响因子：
--
通讯作者：
J. Kane;G. Honigfeld;J. Singer;H. Meltzer
中科院分区：
文献类型：
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作者：
J. Kane;G. Honigfeld;J. Singer;H. Meltzer
对使用神经阻滞剂充分试验无效的精神分裂症患者的治疗是一项重大挑战。氯氮平是一种非典型抗精神病药物，长期以来一直受到科学界的关注，但其临床开发因伴有粒细胞缺乏症的风险而被推迟。本报告描述了一项多中心临床试验，以评估氯氮平在治疗对神经阻滞剂难治的患者中的疗效。符合《精神疾病诊断与统计手册》第三版（DSM - III）的精神分裂症患者，在对至少三种不同的神经阻滞剂无反应后，接受了为期六周的氟哌啶醇前瞻性单盲试验（平均剂量为61±14毫克/天）。病情仍未改善的患者随后以双盲方式随机分配接受氯氮平（最高900毫克/天）或氯丙嗪（最高1800毫克/天）治疗六周。268名患者进入双盲比较。当使用先验标准时，30%接受氯氮平治疗的患者被归类为有反应者，而接受氯丙嗪治疗的患者中这一比例为4%。氯氮平在简明精神病评定量表、临床总体印象量表和住院患者护士观察量表上有显著更大的改善；这种改善包括“阴性”症状区域以及阳性症状区域。尽管在这项相对较短的研究期间没有发生粒细胞缺乏症病例，但在我们看来，明显增加的相对风险要求氯氮平的使用仅限于选定的难治性患者。
The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge. Clozapine, an atypical antipsychotic drug, has long been of scientific interest, but its clinical development has been delayed because of an associated risk of agranulocytosis. This report describes a multicenter clinical trial to assess clozapine's efficacy in the treatment of patients who are refractory to neuroleptics. DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospective, single-blind trial of haloperidol (mean dosage, 61 +/- 14 mg/d) for six weeks. Patients whose condition remained unimproved were then randomly assigned, in a double-blind manner, to clozapine (up to 900 mg/d) or chlorpromazine (up to 1800 mg/d) for six weeks. Two hundred sixty-eight patients were entered in the double-blind comparison. When a priori criteria were used, 30% of the clozapine-treated patients were categorized as responders compared with 4% of chlorpromazine-treated patients. Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale, Clinical Global Impression Scale, and Nurses' Observation Scale for Inpatient Evaluation; this improvement included "negative" as well as positive symptom areas. Although no cases of agranulocytosis occurred during this relatively brief study, in our view, the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients.