Will Genotyping and Phenotyping Methods Replace TDM in the Future?

Like for other drugs, there is a large inter-individual variability of the plasma concentrations of psychotropic drugs for a given dose, which is the main rationale for therapeutic drug monitoring. TDM is performed to avoid toxicity (due to high and poorly tolerated plasma levels) and inefficacy (due to low and ineffective plasma levels). Within the last decade, a large amount of studies in pharmacogenomics allows us to understand the importance of genetic and environmental factors on the disposition of drugs in the organism. Thus, several genotyping and phenotyping methods now allow the determination of the activity of several key enzymes involved in the pharmacokinetics of drugs, in particular those of the cytochrome P450 family. Proposals of genotype specific dosages of drugs have been made (i.e. a low dose for the poor metabolizers and a high dose for the ultrarapid metabolizers), which will lead to, admittedly, equivalent plasma concentrations in all patients. The question arises whether these genotyping and phenotyping methods could replace TDM in the future. Arguments in favor or against this hypothesis will be presented and discussed.