Pharmacogenomics
Loren Bonner
Could genetic testing be used to reduce the trial and error that patients with depression—especially major depressive disorder—so often come up against when finding the right medication for treatment?
Researchers of a new study published in JAMA on July 12, 2022, set out to determine whether pharmacogenomic testing affects antidepressant medication selection and if such testing leads to better clinical outcomes for individuals with major depressive disorder. Their findings reveal that not all patients—at this time—benefit from testing. However, pharmacogenomic testing could reveal a meaningful piece of information that can influence care for a subset of patients.
“There were positive outcomes [from the trial],” said David Oslin, MD, lead author of the study. “But these were not robust enough for me to say test everyone before starting an antidepressant.”
In the control arm of the randomized clinical trial of 1,944 patients with major depressive disorder, about 20% of those started on an antidepressant began a medication with a significant drug–gene interaction.
“Those are the patients we are trying to assist with a test like this,” said Oslin, who is an assistant professor of psychiatry at the University of Pennsylvania Medical Center and a physician at the Philadelphia Veterans Affairs Medical Center.
Thomas Smith, PharmD, associate professor of pharmacy practice and pharmacogenomics at Manchester University in Indiana, who was not involved with the study, noted that even small, incremental improvements for patients with major depressive disorder can be substantial when viewed at the individual level.
Meaning of results
Oslin said one of the biggest take-home messages from the pragmatic study, which was conducted at several Veterans Affairs medical centers across the country, was that education about pharmacogenomics testing for providers and patients is critical.
“Otherwise, there were lots of misunderstandings about the [pharmacogenomic] test and what information it provided,” said Oslin. For instance, many providers thought the test results would assist in selecting a medication that would provide better patient response. “Rather, the test provided information about the metabolism of medications, not effectiveness,” Oslin said.
“The trial may have had different results if all clinicians were well versed in how to best use pharmacogenomics results,” said Smith. “Pharmacogenomics is truly an individual level intervention, therefore if clinicians were to target those who would have the highest potential for using pharmacogenomics testing, that would influence care the most. That is typically how I believe most clinicians operate.”
Smith was also surprised that adverse drug reactions were not evaluated in the study. “This is the other side of the coin that pharmacogenomics can impact,” he said. “Many patients in the pharmacogenomics group may not have had significant difference in remission but could have had significantly fewer adverse drug effects or less impairing adverse drug effects.”
Smith also thinks pharmacogenomics testing is an area where pharmacists can emerge as leaders.
“The reports from commercial pharmacogenomics companies are relatively easy to use,” he said.
“However, there is a lot of context and deeper understanding of the meaning of the results when you combine pharmacology skills, drug literature evaluation skills, and knowledge of drug–gene and drug–drug interactions. Pharmacists are the providers who currently have this unique skill set.”
Oslin added pharmacists will play a key role in the interpretation of these tests and the educational efforts, especially as interest in using these kinds of tests grows.
Advancing care
Overall, Thomas said he found the results of the study to be positive for the use of pharmacogenomic testing, as long as it’s fiscally reasonable for the patient.
“With pharmacogenomics testing, this trial showed we can get better, faster results for [major depressive disorder]. For these patients, more quickly reaching remission can be paramount,” said Thomas.
While this study trial did not home in on any specific population, eventually clinicians could begin to target those who might benefit the most from pharmacogenomic testing and perhaps see a difference in their clinical outcomes.
“I think [this trial] can be used as a tool to present to clinicians who are skeptical of pharmacogenomics and its use in a real-world fashion,” said Thomas. “Many may dismiss the more basic science—related literature on pharmacogenomics because it does not demonstrate practicality in the clinic. However, this article is one of a growing body of literature that does show meaningful improvement in a disease state that we seemed to have stalled out on in terms of advancing care.” ■