Waddington J L, Scully P J, O'Callaghan E
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
Schizophr Res. 1997 Dec 19;28(2-3):207-22. doi: 10.1016/s0920-9964(97)00115-1.
Over almost four decades, few fundamentally different antipsychotic drugs evolved to challenge classical neuroleptics as the mainstay of the pharmacotherapy of schizophrenia. However, the recent re-emergence of clozapine, together with the emergence of risperidone, portends an increasing number of new antipsychotics which are now either traversing the stages of regulatory approval or else well-advanced in clinical development. This article first evaluates the significance of clozapine and risperidone; it then reviews some of the new antipsychotics and how they might be classified vis-a-vis potential advantages for patients, outlines putative mechanisms and new therapeutic targets, and considers whether such agents may act on any disease process inherent to schizophrenia. One fundamental issue is the extent to which the new antipsychotics might shift materially the risk benefit balance towards intervention, not just at the earliest possible stage following the onset of psychosis but at a yet earlier, 'prodromal' phase of the disorder where there is a considerably greater likelihood of 'treating' behavioural disturbances that prove not to be the harbingers of psychotic illness.
在近四十年里，几乎没有本质上不同的抗精神病药物出现，能挑战经典抗精神病药物作为精神分裂症药物治疗的支柱地位。然而，最近氯氮平的重新出现，以及利培酮的出现，预示着越来越多的新型抗精神病药物，它们现在要么正处于监管审批阶段，要么在临床开发中进展顺利。本文首先评估氯氮平和利培酮的重要性；然后回顾一些新型抗精神病药物，以及相对于对患者的潜在优势它们可能如何分类，概述假定的机制和新的治疗靶点，并考虑这些药物是否可能作用于精神分裂症固有的任何疾病过程。一个基本问题是，新型抗精神病药物在多大程度上可能实质性地将风险效益平衡转向干预，不仅是在精神病发作后的最早阶段，而且是在该疾病更早的“前驱”阶段，在这个阶段“治疗”那些最终未发展为精神病性疾病先兆的行为障碍的可能性要大得多。
