Drug treatments for schizophrenia - past, present and future.
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.