PGx Testing: What You Need to Know for Your Practice

 For people with depression, anxiety, ADHD or other mental health conditions, medication may be a vital element of treatment.

Yet, as many healthcare providers can attest, some patients try multiple mental health medications and at different dosages without experiencing a reduction in symptoms. Or some experience side effects that cause them to want to stop taking the medication.

Pharmacogenomic (PGx) testing presents healthcare providers with an opportunity to  use genetics to help personalize a patient’s treatment plan, as someone’s genetic makeup is something that they can’t see by just examining patients.

What is PGx testing?

 Pharmacogenomic (sometimes called pharmacogenetic) tests are a type of genetic test. They do not diagnose a genetic disease. Instead, these tests look at how genetic variations may affect metabolism or response to certain medications.

“A pharmacogenomic test is an assessment of genetic variants that are known or thought to impact how a drug is metabolized by our bodies (pharmacokinetics) or how the drug acts on our bodies (pharmacodynamics),” according to an article on the National Alliance on Mental Illness (NAMI) website. “…Pharmacogenomic testing involves the collection of a DNA sample from a patient by blood draw, cheek swab, or saliva sample. The sample is sent to a laboratory that performs the genetic analyses and returns a report of the findings back to the ordering health care provider and/or the patient.”

PGx tests may help inform medication selection and dosing, although these tests cannot identify exactly which medications or doses will work for a patient. That’s because there are many factors that can influence how your body responds to certain medications. These include drug-drug interactions, food-drug interactions, environmental factors such as lifestyle, and many other factors that healthcare providers consider.

Who makes a good candidate for PGx testing?

 Individuals who are being considered for certain medications, changes to medications, or dose adjustments may be candidates for pharmacogenomic testing. Additionally, while there are no current guidelines that identify who would be good candidates for pharmacogenomic testing, some candidates who may be appropriate for pharmacogenomic testing include:

• Patients whose medications have failed them. Patients with one or more medication failures or patients who are experiencing lower than desired medication response.
• Elderly patients and those with liver damage: Elderly patients and patients with liver damage may have impaired production of liver enzymes, which can affect the rate a drug is metabolized and intensify the effects of genetic variations. GeneSight® testing may help healthcare providers by informing on which medications may require dose adjustments based on a patient’s genetics, which can be used in addition to their revised dosing range for these patients. The GeneSight test has also been shown to significantly reduce polypharmacy (the taking of multiple medications), which can be common in elderly patients.
• Patients who are very sensitive to medications: Side effects from medications may result from the way a drug interacts with your body, the way your body impacts a drug, or psychological manifestations (i.e. nocebo effect). Many healthcare providers use the GeneSight test to shed light on this process for potential solutions.

“We can no longer ignore the statistically proven superiority of pharmacogenomic testing versus treatment as usual,” said Daniel J. Mueller, M.D., Ph.D., head of the Pharmacogenomics Research Clinic and a professor of psychiatry and pharmacology and toxicology at the University of Toronto in Psychiatric News.

“Pharmacogenomics in psychiatry has the most robust evidence to be useful for people who have depression, who are being treated with antidepressants, and who have failed to respond to at least one or more antidepressant trials,” Mueller said. “…Ultimately, this is a once-in-a-lifetime test that can be very useful.”

Treatment decisions and PGx

 Treatment as usual (TAU) entails choosing  treatments based on standard of care, relying on clinical data, and documenting treatment responses until they reach the ideal treatment for each patient. Sometimes treatment as usual entails trialing multiple medications or medication combinations to find something that works for the patient. This is commonly described as a trial-and-error approach.

However, it may take three- to four-weeks, or sometimes longer,  to see an effect with many antidepressants, and the patient may continue to experience symptoms and/or may also start to experience side effects during this period. This process may repeat with each additional new medication and/or dose adjustment, which can lead to months – and even years – of a patient not getting the relief they are seeking.

By analyzing clinically important genetic variations which may impact how a patient metabolizes and responds to certain medications used to treat depression, anxiety, ADHD, and other psychiatric conditions, the GeneSight test provides information about your patient that may help you avoid multiple medication trials. The test can be a tool to augment your experience and expertise, providing additional information that you can’t get from just examining a patient.

“We use MRIs to help diagnose multiple sclerosis. We use lumbar punctures to look at the CSF around the brain and the spinal cord. We use CT scans; we use angiograms. Having GeneSight to look at a patient’s DNA to see the exact backbone of how they are, how they respond to medication, is an invaluable tool,” said Jon Durrani, DO, attending neurologist at the Dayton Center for Neurologic Disorders as well as the Medical Director of Neurology at both Clinton Memorial Hospital and Highland District Hospital.

What does PGx testing analyze?

The information provided by PGx testing includes assaying for a particular genetic variant or multiple variants that have the potential to help inform a healthcare providers treatment decisions.

For the GeneSight Psychotropic test, it utilizes a weighted multi-gene approach to provide  information based on the genetic testing for variants obtained from each patient’s buccal swab. This approach categorizes the more than 60 FDA-approved medications on the report to help inform clinician’s treatment decisions.

There are three color-coded categories in the GeneSight report revealing ascending levels of gene-drug interactions:

• Green (use as directed) – These medications are not associated with any known genetic issues that would be expected to change patient medication outcomes. However, these medications are not guaranteed to work and may not always be the best options, as there are many other factors that influence medication response and susceptibility to side effects, including drug-drug interactions, diet, environmental factors, age, etc.
• Yellow (moderate gene-drug interaction) – These medications may require dose adjustments in order to have the desired effect, may be less likely to work, or may cause side effects.
• Red (significant gene-drug interaction) – These medications are likely to require dose adjustments in order to have the desired effect, may be less likely to work, or may cause side effects. Genetics are expected to have a greater impact on medications in the significant gene-drug interaction category than those that fall into the moderate gene-drug interaction category.

For more information on how to interpret the GeneSight report, click here.

The potential benefits of PGx testing 

The U.S. Department of Veteran Affairs (VA) undertook a study looking at pharmacogenomic (PGx) testing in mental health care. The researchers wanted to know whether access to the genetic test results impacted treatment decisions and improved patient outcomes for those with major depressive disorder (MDD).

The study, conducted independently by the VA and published in the Journal of the American Medical Association (JAMA) in July 2022, found that veterans’ rates of remission from MDD were significantly improved when healthcare providers had access to the GeneSight Psychotropic test.

The study met its objectives by achieving statistically significant results on two co-primary endpoints (endpoints are the main results that are measured at the end of the study). One endpoint showed that over 24 weeks, the PGx-guided group had a 28% greater likelihood of achieving remission from MDD symptoms. The other endpoint showed that patients in the PGx-guided group were less likely to be prescribed medications with predicted gene-drug interactions, compared to the treatment as usual group, within the first 30 days after being assigned to a group.

“The study found a marked shift in prescribing away from medications with significant drug-gene interactions or moderate drug-gene interactions,” according to the VA story about the study. “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.’”

The results of the study found that over 24 weeks, the patients who underwent GeneSight testing saw greater depression remission, depression response, and symptom improvement compared with patients receiving treatment as usual.

Along with the PRIME Care study, the clinical validity, clinical utility and economic utility of the GeneSight Psychotropic test have been evaluated in multiple peer-reviewed publications.

For more information about how GeneSight can support you in your clinical practice, visit our overview page at https://genesight.com/for-clinicians/.

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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. 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.