Eur Psychiatry. 1997;12 Suppl 5:321s-6s. doi: 10.1016/S0924-9338(97)83575-4.
Various historical aspects of resistant schizophrenia are described: limitations of treatment efficacy, attempts at proposing therapeutic strategies in non-responding patients, first attempts to define resistance in schizophrenia, and first attempts to distinguish resistance factors. Interest in treatment-refractory schizophrenia was stimulated by several studies in the period 1985-1990, including a pivotal study of clozapine. The need to include biological and psychosocial factors when defining resistance was emphasised by a group who defined a systematic approach to treatment resistance in schizophrenia, including degrees of resistance. The concept of a continuum from full remission to complete refractoriness was proposed by an international study group in 1990. Difficulties in identifying patients with refractory schizophrenia include: variability of schizophrenia diagnostic criteria, lack of consensus concerning good treatment practice with neuroleptic agents, and confusion between resistance, chronicity and severity. A better definition of refractoriness is needed, not only for pharmacological studies but also for a more precise characterisation of a possible subgroup of schizophrenia termed 'Kraepelinian'.
治疗效果的局限性，为无应答患者提出治疗策略的尝试，首次尝试定义精神分裂症的耐药性，以及首次尝试区分耐药因素。1985 年至 1990 年期间的几项研究激发了人们对治疗抵抗性精神分裂症的兴趣，其中包括氯氮平的一项关键研究。当定义耐药性时，需要包括生物和心理社会因素，这一点被一个定义精神分裂症治疗抵抗系统方法的小组强调，包括耐药程度。1990 年，一个国际研究小组提出了从完全缓解到完全耐药的连续统概念。确定耐药性精神分裂症患者的困难包括：精神分裂症诊断标准的可变性，关于神经阻滞剂良好治疗实践的共识缺乏，以及耐药性、慢性和严重程度之间的混淆。需要更好地定义耐药性，不仅用于药理学研究，而且用于更精确地描述所谓的“克雷丕林式”精神分裂症的一个可能亚组。
