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Genetics explain 42% of antidepressant response

Posted on 03/04/2013
Genetics

A new study led by King's College London reveals for the first time how much response to antidepressant medication is influenced by an individual’s genetic make-up. 

Previous research from the STAR*D trial funded by the National Institute of Mental Health found that only approximately one-third of patients respond within their initial antidepressant medication and about one-third of patients do not have an adequate clinical response after being treated with several different medications. Therefore, identifying predictors of antidepressant response could help to guide the treatment of this disorder.

In the new study published in Biological Psychiatry, researchers estimated the magnitude of the influence of common genetic variants on antidepressant response using a sample of 2,799 antidepressant-treated subjects with major depressive disorder and genome-wide genotyping data.

They found that genetic variants explain 42% of individual differences, and therefore, significantly influence antidepressant response.

Dr. Katherine Tansey, from the Department of Social, Genetic and Developmental Psychiatry (SGDP) at King's Institute of Psychiatry and first author of the paper says: "Many previous studies have searched for genetic markers that may predict antidepressant response, but have done so despite not knowing the contribution of genetic factors. Our study quantified, for the first time, how much response to antidepressant medication is influenced by an individual’s genetic make-up.” 

Dr Tansey adds: “While we know that there are no genetic markers with strong effect, this means that there are many genetic markers involved. While each specific genetic marker may have a small effect, they may add up to make a meaningful prediction.” 

Dr. John Krystal, Editor of Biological Psychiatry, says: “We have a very long way to go to identify genetic markers that can usefully guide the treatment of depression. There are two critical challenges to this process. First, we need to have genomic markers that strongly predict response or non-response to available treatments. Second, markers for non-response to available treatments also need to predict response to an alternative treatment. Both of these conditions need to be present for markers of non-response to guide personalized treatments of depression.”

He added: “Although the Tansey et al. study represents progress, it is clear that we face enormous challenges with regards to both objectives. For example, it does not yet appear that having a less favorable genomic profile is a sufficiently strong negative predictor of response to justify withholding antidepressant treatment. Similarly, there is lack of clarity as to how to optimally treat patients who might have less favorable genomic profile.”

Paper reference: Tansey, K. et al. “Contribution of Common Genetic Variants to Antidepressant Response” Biological Psychiatry, Volume 73, Issue 7 (April 1, 2013) doi: 10.1016/j.biopsych.2012.10.030

For further information, please contact Seil Collins, Press Officer, Institute of Psychiatry, King’s College London, email: seil.collins@kcl.ac.uk or tel: 00 44 207 848 5377

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