Pickar D, Owen R R, Litman R E, Konicki E, Gutierrez R, Rapaport M H
Section on Clinical Studies, National Institute of Mental Health, Bethesda, Md. 20892.
Arch Gen Psychiatry. 1992 May;49(5):345-53. doi: 10.1001/archpsyc.1992.01820050009001.
Twenty-one patients with schizophrenia who met criteria for neuroleptic treatment resistance or intolerance participated in a crossover, placebo-controlled, double-blind comparison of long-term typical neuroleptic and clozapine treatment. Clozapine significantly reduced total as well as positive and negative symptoms in comparison with both fluphenazine and placebo. Of the 21 patients, eight (38%) showed clozapine superiority on the basis of prospective response criteria. High levels of extrapyramidal side effects during fluphenazine treatment and later onset of illness were clinical predictors of clozapine superiority. Clozapine and fluphenazine equally reduced plasma homovanillic acid levels in comparison with placebo, although fluphenazine but not clozapine increased plasma prolactin level. A striking biologic difference between clozapine and fluphenazine was clozapine's enhancement of indexes of noradrenergic activity. Superior clozapine response was predicted by low ratios of cerebrospinal fluid homovanillic acid to 5-hydroxyindoleacetic acid, consistent with the notion that balance between dopaminergic and serotoninergic systems is important for clozapine's mechanism of action.
21名符合抗精神病药物治疗抵抗或不耐受标准的精神分裂症患者参与了一项交叉、安慰剂对照、双盲试验，比较长期使用传统抗精神病药物和氯氮平治疗的效果。与氟奋乃静和安慰剂相比，氯氮平能显著减轻总体症状以及阳性和阴性症状。21名患者中，8名（38%）根据前瞻性反应标准显示氯氮平疗效更优。氟奋乃静治疗期间锥体外系副作用水平较高以及起病较晚是氯氮平疗效更优的临床预测因素。与安慰剂相比，氯氮平和氟奋乃静均能同等程度降低血浆高香草酸水平，不过氟奋乃静会升高血浆催乳素水平，而氯氮平不会。氯氮平和氟奋乃静之间一个显著的生物学差异是氯氮平增强了去甲肾上腺素能活性指标。脑脊液高香草酸与5-羟吲哚乙酸的低比率可预测氯氮平反应更佳，这与多巴胺能和5-羟色胺能系统之间的平衡对氯氮平作用机制很重要这一观点一致。
