Antidepressant drug discovery in the postgenomic era

The progress made in genome research raises the question whether the new knowledge bases that have emerged may also lead to better antidepressants. The past has seen many remarkable improvements over traditional drugs, but not a real breakthrough. More recently hypothesis-driven research in depression has focussed upon stress-hormone regulation as a possible target, but validation of new drugs is not yet in sight. In parallel, we see an upsurge of systematic unbiased research in a biotechnology-driven drug discovery effort. This research can only lead to results if clinical research adapts to these new demands by phenotyping depressed patients not only according to psychopathological characteristics but also by utilising functional (e.g. neuroendocrine, neuropsychological, neurophysiological, neuroimaging and clinical drug response) data that are to be correlated with data from genotyping. To achieve the goal of genotype/phenotype-based differential therapy, large-scale efforts with regards to both patient samples and genotyping capacities are needed. In the long term, increasingly detailed patient information, if translated into specific pharmacological treatments, will lead to customized drugs and thus to a partial fragmentation of the antidepressant market. Concurrently, the improved genotyping/phenotyping efforts will also lead to more widely applicable drugs that promise to avoid side effects and refractoriness and also to hasten the time to onset of action. Once these goals are achieved notorious undertreatment of depression may come to an end.