44 The major issue in the domain of pharmacokinetics is not whether the CYP450 genes have a role in the metabolism of antidepressants, which they do, but if sufficiently solid evidence exists that justify the benefits of genetic

testing for them routinely in the clinic. For those benefits to be documented, the EGAPP Working Group recommends “adequately powered, randomized controlled clinical trials that compare patient outcomes when treatment is informed by genotyping tests versus empirical treatment. Because Inhibitors,research,lifescience,medical depression is prevalent and is an important public health issue, and because SSRIs are widely prescribed, such trials are feasible and essential to determine best management practices with respect to CYP450 testing.” It is, however, challenging to obtain competitive

funding for such studies. The conundrum here is that, while such NVP-BGJ398 molecular weight studies are critically needed for translation of research to practice to occur, they are not designed to test a conceptually novel hypothesis. Work that is not hypothesis-driven tends not to fare well in the fierce competition Inhibitors,research,lifescience,medical for research funds, which is only getting worse.45 In our opinion it is unlikely that the necessary funding, which is required Inhibitors,research,lifescience,medical for large, definitive translational treatment studies, will be allocated to this type of research in the foreseeable future. , unless a concerted effort is made to fund studies that are required to accelerate the translational pathway from medical knowledge to clinical practice. We are hopeful that such studies might fall under the domain of the recently proposed – and much needed – National Center for Advancing Translational Sciences (NCATS).46 Conclusions The gap from research Inhibitors,research,lifescience,medical to translation is still vast in the area of pharmacogenomics of antidepressants, in spite of over a decade of intensive work.47-55 Two major steps need to occur before depressed patients can benefit from genomic tools for Inhibitors,research,lifescience,medical the optimization of their treatment. The first is that existing research findings need to be further solidified, and current controversies and disparate results must be understood and integrated into a universally accepted body of knowledge.

That is what is the field is currently dealing with in the domain of pharmacodynamics – or drug effects. The second step is in the area of bringing ADAMTS5 accepted research findings into practice. The issue in this domain is not whether there is solid scientific evidence; it is in the realm of cost-benefit: will genetic testing, even though logical and rational, be indeed clinically beneficial so that it ought to become part of routine clinical care? This is the locus of the translational gap in the domain of pharmacokinetics. Overall, pursuit of a scientific basis to choose a specific drug, maximizing therapeutic effects and minimizing ADRs, is so important that the pharmacogenomics of depression has become a burgeoning area of research.