Genetic factors play a significant role in predicting an individual’s response to a drug. The response may be the desired therapeutic effect of the drug and also may be the undesirable development of adverse effects. This relationship between genes and drug response interests the pharmacogeneticist. This article aims to give an overview of the exciting discoveries made so far in the field of psychiatry, particularly concerning the response to antidepressants and antipsychotics, as well as to mention some of the more recent findings. The ultimate goal of pharmacogenetics is to provide medication “tailored” to the individual based on their genetic profile, and although this may currently seem a distant target, it has already begun to raise ethical questions, which also are discussed.
Basu A, Tsapakis EM, Aitchison KJ. Current Psychiatry Reports 2004; 6: 134-142.
DOI: 10.1007/s19920-004-0053-5
Individual genetic variation accounts for some of the variability in response to drugs used routinely in clinical psychiatry. Psychopharmacogenetics focuses on how polymorphisms in genes affecting the mechanism of action of a drug’s effect and/or metabolism (both peripheral and central) can influence an individual’s clinical response to the drug, in terms of both therapeutic efficacy and adverse effects. Pharmacogenetics promises to be of substantial help in the field of psychiatric pharmacotherapy, but before research findings can be applied to clinical practice, ethical and methodological problems have to be addressed and overcome. This review summarises the most robust findings in the field and outlines how psychopharmacogenetic studies could lead to treatment individualisation.
Tsapakis EM, Basu A, Aitchison KJ. Clinical relevance of discoveries in psychopharmacogenetics. Advances in Psychiatric Treatment, 10:455-465.
GENDEP: A multicentre European pharmacogenomics study of antidepressants. http://gendep.iop.kcl.ac.uk/results.php
See also:
Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietschel M, Mors O, Hauser J, Maier W, Kozel D, Henigsberg N, Barreto M, Placentino A, Dernovsek MZ, Schulze TG, Kalember P, Zobel A, Czerski PM, Larsen ER, Souery D, Giovannini C, Gray JM, Lewis CM, Farmer A, Aitchison KJ, McGuffin P, Craig I. (2009) Genetic predictors of response to antidepressants in the GENDEP project. Pharmacogenomics Journal (advance online publication 14 April 2009; doi: 10.1038/tpj.2009.12)
http://www.nature.com/tpj/journal/vaop/ncurrent/abs/tpj200912a.html
Uher R, Farmer A, Maier W, Rietschel M, Hauser J, Marusic A, Mors O, Elkin A, Williamson RJ, Schmael C, Henigsberg N, Perez J, Mendlewicz J, Janzing JGE, Zobel A, Skibinska M, Kozel D, Stamp AS, Bajs M, Placentino A, Barreto M, McGuffin P, Aitchison KJ (2008). Measuring Depression: comparison and integration of three scales in the GENDEP study. Psychological Medicine, 38, 289-300 (online first 09 Oct 2007, doi: 10.1017/S0033291707001730).
http://journals.cambridge.org/action/displayAbstract?aid=1661084
Huezo-Diaz P*, Uher R*, Smith R, Rietschel M, Henigsberg N, Marusic A, Mors O, Maier W, Hauser J, Souery D, Placentino A, Zobel A, Larsen ER, Czerski PM, Gupta B, Hoda F, Perroud N, Farmer A, Craig I, Aitchison KJ, McGuffin P (2009) Moderation of antidepressant response by the serotonin transporter gene. Br J Psychiatry, in press. *joint first authors
Uher R, Mors O, Hauser J, Rietschel M, Maier W, Kozel D, Henigsberg N, Souery D, Placentino A, Perroud N, Dernovsek MZ, Strohmaier J, Larsen ER, Zobel A, Leszczynska-Rodziewicz A, Kalember P, Pedrini L, Linotte S, Gunasinghe C, Aitchison KJ, McGuffin P, Farmer A (2009) Body weight as a predictor of antidepressant efficacy in the GENDEP project. J Affective Disorders, in press.
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