Refractory schizophrenia: Historical and currently prevailing criteria and definitions.
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'.
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