Major depressive disorder can be challenging to treat, especially when the medications prescribed don’t work as anticipated. Patients can get frustrated trying different medications and different dosages.
“MDD [Major Depressive Disorder] is one of the most common conditions associated with military service and combat exposure, increases suicide risk, and worsens the course of common medical conditions, making it a leading cause of disability and mortality,” according to the Precision Medicine in Mental Health Care (PRIME Care) study website. In fact, the VA estimates that one in eight to 10 veterans has major depression, requiring treatment with psychotherapy and/or antidepressants.
Now, the U.S. Department of Veterans Affairs (VA) has published the results of the PRIME Care study, which used the GeneSight test, in the Journal of the American Medical Association (JAMA).
According to the study, MDD remission rates were significantly improved and fewer patients were likely to be prescribed medications with predicted gene-drug interactions when clinicians had access to GeneSight Psychotropic test results.
“The findings of this study will have far-reaching clinical implications for patients around the world,” Karen Flaherty-Oxler, medical center director for the Corporal Michael J. Crescenz VA Medical Center (CMCVAMC), told Genetic Engineering & Biotechnology News.
Largest PGx RCT ever conducted in mental health
The PRIME Care study is the largest pharmacogenomic (PGx) randomized controlled trial (RCT) ever conducted in mental health. The study investigated whether access to genetic testing results impacted treatment decisions and improved patient outcomes for those with MDD.
In the PRIME Care study, 1,944 veteran patients with MDD received the GeneSight test and were randomized to receive results immediately (GeneSight test arm) or after 24 weeks (treatment as usual arm). The study met its objective by achieving statistically significant results on both co-primary endpoints.
Myriad Genetics provided the GeneSight tests for the study.
Co-primary endpoint: Patients more likely to achieve remission in GeneSight arm
Remission represents a reduction in symptoms and return to normal or near-normal function, which is considered the optimal treatment goal for both providers and patients.
Yet, finding a medication that enables your patient to achieve remission can sometimes feel as challenging as finding a needle in a haystack. What happens when the first medication you prescribe doesn’t allow your patient to achieve remission? And then the next one? And the next one?
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project showed that fewer than 40% of patients with depression achieved remission using their first prescribed medication.
Also, with each additional medication trial, the chance of remission decreased:
- Only 31% achieved remission after their second medication trial
- Only 14% achieved remission after their third medication trial
The PRIME Care study considered remission as one of its co-primary endpoints. The study showed that over 24 weeks, the group whose clinicians had access to the GeneSight test had a 28% greater likelihood (odds ratio = 1.28, 95% confidence interval 1.05-1.57, p=0.02) of achieving remission from MDD symptoms.
Remission in the study was defined as a score of five or less on the PHQ-9 depression symptom questionnaire.
“The study showed a meaningful increase in the likelihood of achieving remission for patients whose providers had access to GeneSight test results,” said Holly Johnson, PhD, director of Medical Information for Mental Health, Myriad Genetics.
Co-primary endpoint: Patients less likely to be prescribed medications with predicted gene-drug interactions in GeneSight arm
Gene-drug interactions are important because they can inform on a patient’s ability to metabolize or respond to a certain medication. This information can help you understand how patient’s genes may affect their outcomes with medications commonly prescribed to treat depression, anxiety, ADHD and other psychiatric conditions.
The GeneSight test provides this gene-drug interaction information to give clinicians insight about which medications may require dose adjustments, may be less likely to work, or may have an increased risk of side effects based on your patient’s genetic makeup.
The PRIME Care study’s other co-primary endpoint showed that patients in the treatment as usual arm were approximately two-fold more likely (odds ratio = 2.08, 95% confidence interval 1.52-2.84, p=0.005) to be prescribed medications with substantial predicted gene-drug interactions compared to the GeneSight test arm in the first 30 days after randomization.
Secondary endpoints: Response & symptom improvement
The secondary endpoints of response and symptom improvement also showed statistically significant improvements in the GeneSight arm compared to the treatment as usual arm over the 24-week period.
Response is considered a greater than 50% decrease in the patient’s PHQ-9 total score. Symptom improvement is considered the decrease in PHQ-9 score based on the group average.
Adding to the growing body of evidence
PRIME Care is the latest clinical study to support the utility of the GeneSight test. The findings from this independently conducted RCT complement the data from previous studies published in peer-reviewed journals assessing the GeneSight test and depressive treatment outcomes, including a recent meta-analysis. 1-11
This meta-analysis assessed data from four prospective GeneSight clinical utility trials 1-4 and found access to the GeneSight test significantly improved depressive symptoms, response rates, and remission rates compared to treatment as usual.5
As PRIME Care, and other studies show, the combinatorial approach used by the GeneSight test may be used to augment your knowledge, patient evaluation, and experience with genetic information that can help inform treatment decisions.
For more information about this and other topics, please visit:
https://genesight.com/for-clinicians/clinical-studies/
https://genesight.com/white-papers/how-do-i-choose-patients-for-genesight-testing/
Our articles are for informational purposes only and are reviewed by our Medical Information team, which includes PharmDs, MDs, and PhDs. Do not make any changes to your current medications or dosing without consulting your healthcare provider.
The GeneSight test must be ordered by and used only in consultation with a healthcare provider who can prescribe medications. Not all patients who receive the GeneSight test will be prescribed medications with no or moderate gene-drug interactions, and not all will see improvements in symptoms, achieve response, or achieve remission. As with all genetic tests, the GeneSight test results have limitations and do not constitute medical advice. The test results are designed to be just one part of a larger, complete patient assessment, which would include proper diagnosis and consideration of your medical history, other medications you may be taking, your family history, and other factors.
If you are a healthcare provider and interested in learning more about the GeneSight test, please contact us at 855.891.9415. If you are a patient, please talk with your doctor to see if the GeneSight test may be helpful.
Published: October 3, 2022
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About the PRIME Care Study
The study included 1,944 veteran patients with moderate to severe depression (PHQ-9 score >9) with at least one prior treatment exposure were enrolled in the study. The patients were provided treatment at 22 VA Medical Centers across the country.
Entry criteria involved intent to start or switch an antidepressant, with the control group not receiving GeneSight results to inform prescribing. Patients were divided into two arms: the GeneSight arm and the treatment as usual (TAU) arm.
The study was a pragmatic, randomized controlled trial. All patients were tested with GeneSight on day 1, but patients in the TAU group did not receive their results until after the 24-week visit, while clinicians treating the patients in the GeneSight arm received their results within a few days of the test being administered.
The study evaluated two co-primary endpoints: remission over 24 weeks (defined by PHQ-9 ≤5) and use of medications with predicted gene-drug interactions in the 30-day period after randomization. Secondary endpoints included response and symptom improvement.
The patients enrolled in the study comprised a difficult to treat population with 58% diagnosed with comorbid PTSD and 30% experiencing treatment refractory depression, factors that can reduce the likelihood of achieving remission in MDD patients. Importantly, all key demographic variables were balanced between the treatment groups.