Pharmacogenetic methods for rational drug choice

Pharmacogenetics explores the genetic determination of drug response (therapeutic as well as side-effects). Starting point is the marked interindividual variation in response to drugs, and the lack of valid clinical predictors of drug response. Some reasons argue for the impact of interindividual genetic variation on differential drug response. On the other hand, there is some evidence of familial similarities in drug response; we also know that most of the targets of drugs are under genetic variation. Nowadays, the main interest is the screening of DNA variants mainly in functional candidate genes for association with response patterns. Once a candidate is identified it might inform individual rational clinical decisions. The desired long-term goal is individualized medicine. Among the psychotropic drugs, up to now specific antidepressants, neuroleptics and antidementiva were investigated for genetic response determinants with only a very limited number of replicated findings. A more promising area is the impact of genetic variants on plasma levels of psychotropic drugs. The presentation (1) summarizes the opportunities and the current status of knowledge, and (2) reports results emerging from new pharmacogenetic investigations in depression and schizophrenia.