Molecular Methods for Individualization of Psychotropic Drug Treatment

B.      Bondy; P.      Zill

Abstract

Genetic factors are supposed to play a major role for the differences in response to treatment or the incidence of adverse drug effects in psychopharmacotherapy. The aim of pharmacogenetics is to elucidate this variability due to hereditary differences. According to the currently known hypotheses on the mechanisms of drug action, several mutations in genes coding for neurotransmitter-receptors, -degrading enzymes, transport proteins or enzymes of the drug metabolizing system have been identified and investigated in terms of efficacy and adverse drug effects. Although there exists considerable controversy among the results, many studies are supportive for the hypothesis, that psychopharmacogenetics will be helpful in predicting an individuals drug response and identify persons at risk for serious side effects on the basis of the genetic make up. The introduction and inclusion of pharmacogenomics, which is a powerful tool to identify genes affected by drugs, will most likely help to delineate so far unknown drug targets, predict drug responsiveness and adverse reactions and finally propose new hypotheses for both the pathophysiological basis of psychiatric disorders and the mechanisms of psychotropic drug action. This paper briefly overviews the present status of pharmacokinetic and pharmacodynamic aspects in the pharmacogenetics of antipsychotics, antidepressants and lithium ions. Further, a summary on the work investigating genes of the signal transduction cascade, neuronal plasticity and stress response is given.

Keywords: CYP enzymes, Pharmacokinetic, Antipsychotic drug-induced tardive dyskinesia, 5-HT2A receptor, dopaminergic receptor