Pickar D, Owen R R, Litman R E, Hsiao J K, Su T P
National Institute of Mental Health, Experimental Therapeutics Branch, National Institutes of Health, Bethesda, Md 20892.
J Clin Psychiatry. 1994 Sep;55 Suppl B:129-32.
The introduction of the atypical neuroleptic, clozapine, has had widespread influence not only on the treatment of the seriously mentally ill patient, but also on new drug development and on hypotheses of the pathophysiology of schizophrenia. While clozapine differs from traditional neuroleptics in its lack of extrapyramidal side effects (EPS), it also is distinct in its profile of neurotransmitter receptor affinities. In our work examining the clinical and biological effects of clozapine in patients with schizophrenia, we have identified the presence of EPS during typical neuroleptic treatment as a consistent predictor of subsequent good response to clozapine. Further, our data suggest that clozapine should not be reserved for the most chronically ill patients, but rather be utilized in patients with less chronic courses of schizophrenia. Biological predictors of clozapine response are consistent with dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action.
非典型抗精神病药物氯氮平的引入不仅对重症精神病患者的治疗产生了广泛影响，而且对新药研发以及精神分裂症病理生理学假说也有影响。虽然氯氮平与传统抗精神病药物不同，它没有锥体外系副作用（EPS），但其神经递质受体亲和力 profile 也很独特。在我们研究氯氮平对精神分裂症患者临床和生物学效应的工作中，我们发现典型抗精神病药物治疗期间出现 EPS 是随后对氯氮平产生良好反应的一致预测指标。此外，我们的数据表明，氯氮平不应仅保留给最慢性病患者，而应在精神分裂症病程较短的患者中使用。氯氮平反应的生物学预测指标与其作用机制的多巴胺能、5-羟色胺能和去甲肾上腺素能方面一致。
