Drug treatments for schizophrenia — past, present and future

Abstract

The typical antipsychotic drugs, which have been the mainstay of treatment for schizophrenia for many years, are potent antagonists of D₂ receptors. However, their lack of selectivity for D₂ receptors in the mesolimbic areas compared with the nigrostriatal areas of the brain has resulted in an association at therapeutic doses with extrapyramidal side-effects, an increased risk for tardive dyskinesia and increased prolactin levels. Together with other significant side-effects, this profile has limited their acceptability for antipsychotic treatment, resulting in poor compliance, increased risk of relapse and increased severity of disease. A new generation of antipsychotics, the ‘atypicals’, which show greater selectivity for mesolimbic D₂ receptors combined with effects on 5-HT₂ receptors, have demonstrated antipsychotic efficacy, with a significantly lower incidence of extrapyramidal effects than seen with haloperidol, and often at placebo level. The first atypical antipsychotic, clozapine, has been restricted to use in treatment-resistant schizophrenia because of an association with agranwlocytosis. Two other drugs are now available, olanzapine and sertindole, and two others, quetiapine and ziprasidone, are in late-stage development. The profile of these drugs is reviewed, together with future treatment possibilities.

Key Words:

• typical antipsychotics
• atypical antipsychotics
• olanzapine
• risperidone
• quetiupine
• sertindole
• ziprasidone