Pharmacogenomic or genetic testing can help providers avoid prescribing antidepressant medications that may have undesirable outcomes, found a VA study. Pharmacogenomics is the study of how genes affect the body’s response to drugs.

Patients who underwent genetic testing had more positive outcomes, compared with patients in usual care. Over 24 weeks of treatment, the group with genetic testing had in a drop in depression symptoms—with a peak effect at 12 weeks. Each patient in the study had major depressive disorder. Symptoms of that health condition include insomnia, loss of appetite, feelings of sadness and depression, and thoughts of dying by suicide.

Dr. David Oslin, director of the VA VISN 4 Mental Illness, Research, Education, and Clinical Center, located in Philadelphia and Pittsburgh, led the study. He thinks the results will encourage providers to consider using pharmacogenomic testing, with patient consent, to help drive treatment decisions.

“From a VA policy perspective, I don’t think that we would say the study is robust enough that we recommend testing everybody,” says Oslin. “But I think the results favoring a positive effect on treatment, although small, will encourage providers to test patients and get this genetic information. Future research should explore if there are subgroups of patients who would benefit more from testing.”

Focus on metabolizing drugs

In recent years, pharmacogenomic testing has received greater attention as a tool to personalize medication selection and is often used to treat patients with health conditions such as cancer and heart disease. Many in the medical community hope the testing can also be helpful in treating people with major depressive disorder. Research has been limited, however, on demonstrating improved clinical outcomes.

“The genes we tested don’t actually relate to depression,” Oslin says. “They relate to how a person metabolizes the drugs once they’re in the body. Some of these genes will cause the medications to metabolize much faster than normal. Others will cause the drugs to metabolize much slower than normal, which means you’ll end up with a lot of medication in your body.”

The patients enrolled in the study were initiating or switching treatment with an antidepressant drug. The study included nearly 2,000 patients from 22 VA medical centers who were randomized evenly, with half receiving pharmacogenomic testing and the other half getting usual care. Oslin and his colleagues aimed to learn if genetic testing helped patients receive fewer medications with predicted drug-gene interactions and if that produced better outcomes.

A drug-gene interaction is an association between a medication and a genetic variant that may affect a patient’s response to drug treatment. Having that information helps the provider select the appropriate dosage for a specific patient.

The crux of the study

The study found a marked shift in prescribing away from medications with significant drug-gene interactions or moderate drug-gene interactions. Overall, 59% of the patients in the genetic testing group received a medication with no predicted drug-gene interaction, compared with 26% in the control group. The researchers defined that difference as “statistically significant and clinically meaningful.”

Oslin says he went into the study thinking the research team would not see such a dramatic effect in predicted drug-gene interactions. He was “somewhat surprised” by the result. “There was essentially a major shift in avoiding medicines that had a predicted drug-gene interaction,” he says.

“It’s important to realize that the test is not telling you whether the patient is going to respond to the treatment or not,” he adds. “It’s telling you something about how the patient metabolizes the medication. So, it’s not telling me that this is a good medicine for the patient. It’s telling me not to prescribe this medicine, or perhaps to adjust the dosing, because the patient doesn’t metabolize it well.”

More information

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By Mike Richman is the managing editor in VA Research Communications

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Published on Jul. 19, 2022

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