Evolution of the Concept of Treatment-resistant Schizophrenia: Toward a Reformulation for Lack of an Adequate Response

The concept of “resistant schizophrenia” is linked to the development of antipsychotic drugs. Although there were previous attempts, the first definition acknowledged in the scientific literature, was closely linked to the development of clozapine in dichotomic terms of response/no response to previous drug. This article reviews the influence of the psychopharmacologic treatment of schizophrenia on the evolving definition of treatment-resistance. It also addresses other concepts of interest, such as remission and recovery, as well as definitions of schizophrenia in which deterioration is an integral part of the psychopathology, thereby implicitly ruling out the possibility of a complete remission of symptoms. Instead of treatment-resistance, we are suggesting the term “lack of adequate response,” which is closer to operational dimensional models that integrate the idea of a continuum with response levels related to an individual's life expectations, and which allow different pharmacological approaches to be integrated.