October 16, 2012

expert reaction to genetic markers of response to anti-depressants

A large study in PLOS Medicine suggested genetic markers cannot predict which patients with major depression will respond to anti-depressant drugs.

Dr Paul Keedwell, Clinical Lecturer in the Neurobiology of Mood Disorders
and Honorary Consultant Psychiatrist at MRC Centre for Neuropsychiatric Genetics and Genomics, said:

“Currently only about a third of depressed people achieve complete recovery with their first antidepressant of choice. The recovery rate improves after switching from one type to another, but a minority remain “treatment resistant”. There is currently no reliable way of predicting who will respond to which antidepressant to guide treatment. In the largest study to date, it was hoped that researchers would be able to identify genetic predictors. 

“Disappointingly, no genetic variants were identified which reliably predicted response, let alone response to different drug types. There are many possible reasons. Wide variations in depression severity, stress levels and antidepressant types across individuals reduced the chances of finding an association.

“A large multicentre study is needed, perhaps focusing on one or two of the most commonly used antidepressants. However, this would be expensive. It is more likely that data from several modest studies will be pooled, as was done here.

“Arguably, not enough work has been done on using symptom profile, gender and age to predict response. These could be combined with simple psychological lab tests and stress hormone levels. New brain imaging techniques also offer hope. For the foreseeable future, however, antidepressant treatment will have to proceed on a trial and error basis.”

‘Genetic Predictors of Response to Serotonergic and Noradrenergic Antidepressants in Major Depressive Disorder: A Genome-Wide Analysis of Individual-Level Data and a Meta-Analysis.’ by Tansey et al, published in PLOS Medicine on Tuesday 16 October 2012.