Woman sitting in front of laptop with head in hands to illustrate depression
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Testing patients with depression for genetic variants that could interfere with how different antidepressants function could help improve outcomes and prevent side effects to a moderate degree, suggests research led by the University of Pennsylvania.

Initial response to antidepressant drugs is low at 33% or less. Pharmacogenetic testing, which looks at genetic variation in genes that control how drugs are metabolized by the body, has been suggested as a method to improve the rate of response by selecting drugs likely to perform well with minimal side effects.

To date, results from studies of pharmacogenetic testing to help treat depression have shown mixed findings. To try and clarify the usefulness of this kind of testing, David Oslin, director of VA’s VISN 4 Mental Illness, Research, Education, and Clinical Center and a psychiatrist at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, and colleagues carried out a randomized controlled trial in patients with depression. As part of the study, some patients underwent pharmacogenetic testing before treatment was prescribed and some did not.

“The genes we tested don’t actually relate to depression,” Oslin said in a press statement. “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.”

As described in JAMA, 1944 patients with major depressive disorder were included in the study, 1541 of whom completed the study at 24 weeks. Participants were initiating or switching treatment with a single antidepressant and half underwent pharmacogenetic testing before being given a prescription and half were prescribed medication without pharmacogenetic tests.

The team found that rates of prescription of drugs with potential drug-gene interactions was 40% lower in the group guided by pharmacogenetic testing than those receiving usual care. The rates of symptom remission (patients with PHQ-9 scores in the normal, non-depressed range) were somewhat higher in the pharmacogenomic-guided group than in the standard care group at a respective 14.7% vs 11.3% at 8 weeks, 16.5% vs 11.2% at 12 weeks, and 17.2% vs 16.0% at 24 weeks.

“From a VA policy perspective, I don’t think that we would say the study is robust enough that we recommend testing everybody,” noted Oslin. “The results were not a slam dunk, and in fact, an important outcome of the study is that only about 15% to 20% of the patients had genes that would significantly interfere with the prescribed medication. 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.”

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