Pharmacogenetics based therapeutic recommendations in antidepressant drug therapy

Future therapeutic drug monitoring may become a combination of drug concentration analyses and analyses for inherited and acquired molecular variability. Existing clinical data on the impact of CYP2C19 and CYP2D6 polymorphisms were used in a systematic manner to calculate to dose adjustments. For 14 antidepressants at least a doubling of dose in extensive metabolizers versus poor metabolizers would be necessary to compensate for the inherited differences in drug blood concentrations with different studies showing excellent correspondence. From 80 clinical studies on polymorphisms in neurotransmitter receptors, transporters and signal transduction factors almost none showed any associations with response to therapy or adverse drug effects or associations found could not be replicated in confirmatory studies. This lack of consistency might be due to statistical insufficiencies of the studies combined with moderate or absent functional effects of the studied variants. It appears that the really important genes determining response to therapy of depression still remain to be discovered.