The assessment and management of treatment-resistant schizophrenia in perspective.

Consensus was reached on the five following points: (1) "Treatment resistance" is a term which is widely used, but not adequately defined. In particular, definitions of "responders" and "non-responders" need to be more precise. (2) There is a need to extend the assessment of the results of treatment to include factors such as quality of life and the subjective evaluation by the patient and relatives. (3) Clozapine (Clozaril((R))/Leponex((R))) has become the standard for atypical antipsychotic drugs. The adjective "atypical" is not an exact descriptor. The vague nature of the term leads to confusion with other drugs that are putative atypical antipsychotic agents but have different properties. D(2) dopamine receptor antagonism is the single factor common to all antipsychotic drugs. Antagonism at a specific D(2)-like receptor may underlie the atypical antipsychotic actions of clozapine. Drugs described as being atypical antipsychotics share a relatively low incidence of extrapyramidal side effects. (4) Clozapine is the only drug that produces antipsychotic (therapeutic) effects at doses that do not result, in significant extrapyramidal side effects. This may be due to the fact that antipsychotic efficacy is obtained with clozapine in doses that result in significantly less striatal D(2) occupancy. Other factors including concomitant 5-HT(2) antagonism, may contribute to the lack of motor side effects observed with clozapine treatment. (5) Clozapine is the only drug currently well proven in therapy-resistant schizophrenia, and there is a case for its earlier use in patients who can be anticipated to become therapy resistant. Other antipsychotic therapies remain unproven in this group of patients.