Drug treatments for schizophrenia — past, present and future

Jun 20, 2014International journal of psychiatry in clinical practice

Drug Treatments for Schizophrenia: Past, Present, and Future

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Abstract

Atypical antipsychotics show a significantly lower incidence of extrapyramidal effects compared to haloperidol.

Typical antipsychotics are associated with extrapyramidal side effects and increased prolactin levels.
The lack of selectivity for D2 receptors in certain brain areas contributes to these side effects.
Atypical antipsychotics demonstrate greater selectivity for mesolimbic D2 receptors and effects on 5-HT2 receptors.
Clozapine is limited to treatment-resistant schizophrenia due to its association with agranulocytosis.
Olanzapine and sertindole are currently available, while quetiapine and ziprasidone are in late-stage development.

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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.

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