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Combinatorial pharmacogenomic test may significantly improve MDD outcomes

A combinatorial pharmacogenomic test significantly improved outcomes among patients with major depressive disorder who had at least one prior medication failure, according to results of a randomized controlled trial published in The Journal of Clinical Psychiatry.

“Collectively, the data presented here support the utility of pharmacogenomic testing in patients who are failing their current medications due to genetic reasons,” Michael E. Thase, MD, professor of psychiatry at the Perelman School of Medicine of the University of Pennsylvania, and colleagues wrote. “Identifying these gene-drug interactions can prompt appropriate changes in prescribing to ultimately improve patient outcomes.”

According to Thase and colleagues, clinicians often prescribe based on their own preferences and experiences, as well as on patients’ treatment histories. This often does not lead to patients achieving remission, and consensus exists within the psychiatric community that an improved approach to medication selection is needed for patients with MDD, according to the researchers.

The researchers used data from the Genomics Used to Improve Depression Decisions (GUIDED) trial — a large, blinded, randomized controlled trial — to assess outcomes of the subset of patients who were taking medications with predicted gene-drug interactions and were thus expected to benefit from combinatorial pharmacogenomic testing. They enrolled patients who had an inadequate response to at least one psychotropic medication during the current episode of MDD and then randomly assigned these patients to either treatment as usual (TAU) or a guided-care arm where clinicians used a combinatorial pharmacogenomic test report to inform medication selection.

Among 1,799 patients taking medications subject to gene-drug interactions at baseline, outcomes were significantly improved at 8 weeks for those receiving guided care compared with TAU (symptom improvement = 27.1% vs. 22.1%; P = .029). The response was 27% for guided care vs. 19% for TAU (P = .008), and remission was 18.2% for guided care vs. 10.7% for TAU (P = .003). All outcomes were significantly improved in the guided-care arm vs. TAU when the researchers assessed patients who switched medications.

“Many non-genetic factors may contribute to medication failure,” the researchers wrote. “These factors were not explicitly collected in the GUIDED trial, and thus their impact on patient outcomes cannot be assessed. However, any impact of non-genetic factors should affect both study arms equally due to balanced randomization.” – by Joe Gramigna

Disclosures: Please see the study for all authors’ relevant financial disclosures.