Pharmacogenetics: antidepressant drug response

An individual taking an antidepressant may respond favourably to it, not at all and/or develop significant side effects. The reasons for this individual variation are numerous, but certainly include genetic causes. The study of these genetic variations and their impact on drug response is known as pharmacogenetics, a rapidly expanding field of research. Amongst others, pharmacogenetic findings include an association between the l allele of the serotonin transporter gene (5-HTTLPR) and a better response to selective serotonin reuptake inhibitors and the ability to predict metabolizer status with a high degree of accuracy by genotyping for CYP2D6 and CYP2C19 polymorphisms. In addition, recent discoveries involving genes that regulate the hypothalamic-pituitary-adrenal axis such as FKBP5 are also mentioned. With the arrival of new technology in the form of microarrays, studies are no longer limited to a handful of 'candidate genes' to investigate, but rather the whole genome is now accessible for further examination. Methodological issues are also mentioned, particularly in relation to some findings that are at present unreplicated. The ultimate goal of pharmacogenetics is individualized drug treatment to maximize the chances of a therapeutic response and to minimize the chances of adverse events. If this is to become a reality, well replicated results from the clinical laboratory will need to be transferred to the patient bedside.