Pharmacogenetic Testing Leads to Better Depression Treatment Decisions

According to a new study published in the Journal of the American Medical Association (JAMA) on July 12, pharmacogenetic (PGx) testing measuring a drug’s effect on certain genes can help caregivers make better decisions about whether and what types of antidepressant medications to prescribe to particular individuals.

The Diagnostic Challenge

Antidepressant drugs have proven effective in treating major depressive disorder (MDD). However, selecting the right antidepressant is an imprecise practice. Traditionally, the selection of antidepressants has been based on subjective factors, such as cost or patient and/or provider preferences. This tends to result in a trial-and-error approach, requiring multiple attempts to achieve adequate symptom control. MDD remission rates are also high—about 30 percent after initial treatment.

PGx testing provides information that helps predict a person’s response to a specific medication and/or risk for adverse reactions based on their genetic makeup. This information can be useful in guiding medication and dosing decisions. But while PGx testing continues to gain popularity, its effectiveness remains relatively unproven, including concerns about the clinical validity of particular PGx tests and the quality of PGx laboratory testing.

The Study

Scientists at the Department of Veterans Affairs Medical Center set out to study the impact of PGx testing on MDD drug prescription decision-making. They conducted a clinical trial including 676 clinicians and 1,944 patients enrolled from July 2017 through February 2021, with follow-up ending November 2021. Eligible patients were veterans with MDD who were initiating or switching treatment with a single antidepressant.

The patients were split into two groups: a cohort of 966 MDD patients whose clinicians received results of PGx tests before prescribing medications, and a control group of 978 participants who received traditional MDD care and access to PGx testing results after 24 weeks.

The researchers used Myriad Genetics’s GeneSight Psychotropic PGx test, which includes 64 medications commonly prescribed for depression, anxiety, ADHD, and other psychiatric conditions.

The Findings

The researchers found that patients who received PGx tests before medications were prescribed experienced better outcomes soon after being tested, with a marked shift away from prescribing medications with significant or moderate drug–gene interactions. Overall, approximately 59 percent of the patients in the PGx testing group received a medication with no predicted drug–gene interaction, compared to about 26 percent in the control group.

Specifically, the researchers found statistically significant differences between the two groups in terms of the estimated risks of receiving an antidepressant with no, moderate, and substantial drug–gene interactions that might affect a patient’s reaction to a drug:

Likelihood of Gene–Drug Interaction	PGx Group	Control Group
No	59.3 percent	25.7 percent
Moderate	30 percent	54.6 percent
Substantial	10.7 percent	19.7 percent

The data show that PGx testing for drug–gene interactions led to fewer prescriptions for drugs with predicted drug–gene interactions, versus “usual care.” In other words, providers who understood the associations between a drug and genetic variants that could potentially affect a patient’s response to it enabled physicians to prescribe treatments that were more appropriate for that particular patient. As a result, the group that received PGx testing was more likely to receive a medication with a lower potential for adverse drug–gene interactions.

Although remission rates over 24 weeks were greater among patients in the PGx group, the differences were not significantly greater at the 24th week, at which point 130 patients in the PGx group and 126 patients in the control group were in remission. Thus, the researchers concluded that providing PGx test results only had a small nonpersistent effect on remission rate.

Takeaway

Despite mounting evidence, the day where we rely heavily on PGx testing to individualize treatment has not yet arrived. In 2018, the American Psychiatric Association (APA) concluded that there was insufficient data to support widespread use of PGx to guide antidepressant treatment. The APA cited methodological flaws in the research of Myriad Genetics and other companies that manufacture PGx tests, along with a lack of transparency regarding the algorithms the companies used to derive treatment recommendations from tests that include multiple genetic variations (known as combinatorial tests). However, the results of the recent JAMA study support more widespread use of PGx in psychiatric treatment settings.