Catatan

Over 50 years of pharmacogenetic research have produced many examples of how inherited vari-
ability in drug metabolism can influence individual responses to psychotropic drugs. However, this

knowledge has largely failed to be translated into broadly applicable strategies for improvements

in individual drug treatment in psychiatry. One important argument brought against the wide-
spread adoption of pharmacogenetics as a clinical tool is the lack of available evidence showing its

influence on contemporary clinical praxis and its potential role in improving the risk/benefit ratio

for the patients. Individual drug-metabolizing capacity is assessed by genotyping drug-metaboliz-
ing enzymes. The information gained from genotyping patients may be used to adjust initial and

maintenance drug doses according to genotype. However, even where the consequences of geno-
type on pharmacokinetics are significant and well-known, as in the case of many tricyclic antide-
pressants and several selective serotonin reuptake inhibitors, there is still considerable controversy

as to whether the adjustment of dosage (based upon genetic information) to improve therapeutic
efficacy and/or to reduce the occurrence of adverse events is of any practical importance in clinical
practice. Pharmacogenetic studies can improve our understanding of the functional consequence
of a genetic variant in the clinical setting, and the use of intermediate phenotypes instead of broad
outcome parameters (such as drug response or remission) might improve our knowledge regarding
the clinical response of an individual with a specific genotype to a specific drug. Here, we review
the potential impact of adopting an integrated approach to patient treatment, which combines the

use of intermediate phenotypes that arise from common genetic polymorphisms in drug metabo-
lism enzymes, the monitoring of the therapy progress, and the possibility of pharmacogenetic-
based response prediction in depression.