Pharmacogenomics of antidepressants: Drug discovery, treatment, and ethical considerations

Pharmacogenomics is a new area of medicine that uses the data emerging from the sequencing of the human genome to predict drug responses and to identify new targets for treatment. Pharmacogenomics is of great relevance to depression, a common and complex disorder of unknown cause for which prediction of treatment response and identification of new targets for therapeutics are of crucial importance. The clinical reality is that weeks of continued antidepressant treatment are required before therapeutic effects occur. Moreover, it is not possible to know in advance if a patient is likely to respond to a specific drug. While therapeutic effects take long to emerge, adverse reactions manifest themselves rather soon. This impacts negatively on compliance, leading to incomplete and failed treatments, and potentially disastrous outcomes, such as suicide, which is now the eighth leading cause of death in the United States. The identification of the genomic substrates underlying antidepressant treatment would facilitate not only the formulation of individualized treatment approaches, but also the development of new classes of drugs that would affect those genomic targets more directly than existing compounds, leading to more rapidly effective clinical responses. As the research needed to achieve these goals is being conducted, myriad ethical questions emerge: Which ethnic groups will participate in-and consequently benefit from-such research? How will genomic information related to drug response be handled in ethical, legal, economic, and social terms? Progress in the pharmacogenomics of depression needs to be paralleled by thoughtful consideration of the implications of such work at the individual and societal levels.