How Will Patients React to Medications? The Answer May Be in Their Genes


A study finds that testing genetic variations can predict outcomes and medication blood levels in patients with depression.



A recent study published in Psychiatry Research found that a combinational pharmacogenetic test was a better predictor of medication blood level and patient outcomes than single-gene testing alone.1

Common psychiatric medications for depression and anxiety can react with patients’ genes in ways that inhibit the drugs’ effectiveness. It is possible to test single genes for potential interactions, but Myriad Genetics has developed a test that analyzes gene combinations as well.2 The study found that testing variations in multiple genes led to better, more predictive results.

The study’s lead author was Anthony J. Rothschild, MD, Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School. In the article, he and his coauthors explained the importance of the findings as follows: “This evaluation of clinical validity shows that only the combinational pharmacogenomic test was significantly associated with improved patient outcomes. In addition, the combinatorial pharmacogenomic test was a superior predictor of medication blood levels across a larger group of medications relative to guidelines focused on only CYP2C19 and CYP2D6.”1

The study was based on data from the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial.1 Between 2014 and 2017, the GUIDED trial drew participants from 60 psychiatry and primary care centers around the United States. In order to be eligible, participants needed a major depression disorder diagnosis and a score of 11 or more on the 16-item Quick Inventory of Depressive Symptomatology Scale at screening. They also needed at least 1 failed trial of psychotropic medication during their current depressive episodes.1 Participants were placed blindly into the pharmacogenomic-guided care or conventional treatment arms of the trial for 8 weeks. The researchers then measured and analyzed their outcomes.

The GUIDED trial did have some limitations. It was not a controlled pharmacokinetics study, meaning “blood levels were not controlled for time of intake or medication adherence.”1 As blood levels were only collected at screening, they could not be directly linked to adverse events or other outcomes. Still, the results were promising.

“This analysis demonstrates that the combinatorial approach of the GeneSight test more accurately predicts blood drug levels and identifies more patients with significant gene-drug interactions who would be missed by single-gene testing,” Mark Pollack, MD, chief medical officer of Myriad Neuroscience, said in a statement to the press. “Combinatorial pharmacogenomics like the GeneSight test should become the standard-of-care to help physicians understand gene-drug interactions that could improve care for people with depression, anxiety and other conditions.”2


1. Rothschild AJ, Parikh SV, Hain D, et al. Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. Psychiatry Res. 2021;296:113649.

2. GeneSight psychotropic test’s combinational approach proves better than single-gene testing at predicting patient outcomes and medication blood levels. Global Newswire. February 8, 2021. Accessed March 4, 2021.

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