Unfortunately, antidepressant drug therapy does not work for everyone. But new research finds that improved identification of genomic predicators — that is, how a person’s genetic makeup might impact their response to medication — will help future treatment of depression.
The National Institute of Mental Health’s STAR*D study, the largest and longest study ever conducted to evaluate depression treatment, has determined that only one-third of individuals respond to the first medication prescribed for depression, and that another one-third do not have an adequate response despite being treated with several medications.
Thus, identifying predictors of antidepressant response could help to guide the treatment of this disorder.
A new study, published in Biological Psychiatry, discusses new initiatives for identifying genomic predictors of antidepressant response.
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, said Katherine Tansey, Ph.D., a psychiatric researcher at King’s College, London.
“Our study quantified, for the first time, how much is response to antidepressant medication influenced by an individual’s genetic makeup,” said Tansey.
For the study, 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 percent of individual differences, and therefore, significantly influence antidepressant response.
“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,” Tansey added.
“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,” said Dr. John Krystal, editor of the journal.
“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.”
“Although the Tansey et al. study represents progress, it is clear that we face enormous challenges with regards to both objectives,” he added. “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.”
Although additional research is required, scientists believe they are closing the gap on genomic identifications that can lead to personalized treatment for depression.