Pharmacogenetics in the management of antipsychotic treatment

Genetic factors are likely to contribute to individual variations in treatment response and adverse drug effects. The aim of pharmacogenetics is to elucidate the hereditary differences and to create a personalized, efficacious and less harmful therapy.

According to the supposed mechanisms of drug action, several mutations in genes of receptors, degrading enzymes, or transport proteins have been investigated in relation to treatment response. Although some controversy exists, there is incidence that polymorphisms within genes of the serotoninergic and dopaminergic pathway (e.g 5-HT2A-and DRD3 receptors) may be involved in antipsychotic action.

Concerning adverse effects, classically the EPMS have been considered as the most troublesome ones. For tardive dyskinesia associations were identified with variants in the DRD3 and 5HT2C receptors. Recently evidence emerged that with newer atypical drugs other serious adverse effects, as the metabolic syndrome, are of importance. So far association were reported between allele genetic variants in the promoter region of the 5-HT2C receptor gene and antipsychotic induced weight gain. Other factors, influencing the complete mechanisms of weight regulation, the lipid or glucose metabolism are currently under investigation.

Both, current knowledge and future investigation will contribute considerably in providing genetic markers to decide for a suitable drug and to improve the quality and efficacy of antipsychotic treatment.