Combinatorial Pharmacogenomic Testing Improves Outcomes for Patients Taking Medications With Gene-Drug Interactions in a Randomized, Controlled Trial

Objectives: The GUIDED trial demonstrated that combinatorial pharmacogenomic (PGx) testing significantly improved the rate of response (p=0.007) and remission (p=0.005) and approached significance for symptom improvement (p=0.069). However, these findings may have been diluted by the inclusion of patients taking medications with no predicted gene-drug interactions. Here, we examined outcomes only in patients who entered the study taking medications with predicted gene-drug interactions.

Methods: Patients diagnosed with MDD who failed ≥1 psychotropic medication were randomized to treatment as usual (TAU) or guided-care arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded until after week 8. Medications were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Only patients taking medication(s) with moderate or significant gene-drug interactions at baseline were included (N=786). Outcomes were assessed by arm at week 8 using the 17-item Hamilton Depression Rating Scale (HAM-D17): symptom improvement (% change in HAM-D17), response (≥50% decrease in HAM-D17), and remission (HAM-D17 ≤7).

Results: Among patients taking medication(s) predicted to have gene-drug interactions at baseline, outcomes at week 8 were significantly better for those in the guided-care arm compared to TAU for symptom improvement (27.1% versus 22.1%, Δ=5.0%, p=0.029), response (27.0% versus 19.0%, Δ=8.0%, p=0.008), and remission (18.2% versus 10.7%, Δ=7.5%, p=0.003).

Conclusions: Combinatorial PGx testing significantly improves outcomes among patients with MDD who are failing medications for likely pharmacogenomic reasons.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.