Genes might not be the key to antidepressant success after all

Genetic biomarkers may not help doctors choose the best antidepressants after all, according to research coming out of the NEWMEDS consortium, a partnership of universities and pharmaceutical companies, and published in PLoS Medicine.

Less than half of patients with clinical depression find that they get better with the first antidepressant they are prescribed, delaying their recovery. There have been many stories over the last year about biomarkers, especially genetic biomarkers, forming the basis for potential tests to diagnose depression or predict the outcome of treatment. Being able to do this would help doctors choose the right treatment for the right patient, avoid drugs that might have unpleasant side effects, and improve quality of life for patients and their families, especially those who are at risk of suicide. It could also help the development of new drugs, particularly for those people who do not respond to any antidepressants.

The international research group, led by a team from King's College London's Institute of Psychiatry, analyzed a database of 1,790 people with European ancestry and a diagnosis of clinical depression. The aim was to find out whether there were any genetic differences that could predict which patients would not respond to serotonin reuptake inhibitors (SRIs) or noradrenaline reuptake inhibitors (NRIs), the main two classes of antidepressants. They also looked to see whether any markers could pick out the patients who would respond to one class of drugs or the other. Despite screening more than half a million genetic markers, and cross-checking the results with another large-scale study, they could not find any single variants that were able to predict response to antidepressants overall, or differentiate between responses to SRIs or NRIs.

Rudolf Uher from King's College London's Institute of Psychiatry says: "The large samples we used makes this a definitive study in the field. We found that no single genetic variant, or combination of genetic variants, could predict response to antidepressant treatment. This study stands out against the background of numerous claims from commercial companies that genetic tests could help doctors decide which antidepressant to choose based on the results."

It is still possible that responses to antidepressants are based on rare variants, or on interactions between a number of genetic variants and environmental factors, which is perhaps not surprising as depression is a complex disorder.

The study did not look at responses to specific antidepressant drugs, and further studies would need to draw on a broader base of clinical, genetic, epigenetic, transcriptomic and proteomic information.

- read the press release
- see the abstract