Using a Genetic Test (Combinatorial Pharmacogenomics)To Help Choose Patient-Specific Antidepressants for Depression: a Large, Blinded, Randomized Control Trial

Background: Here we present the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the utility of combinatorial pharmacogenomic (PGx) testing in medication selection for patients with Major Depressive Disorder (MDD).
Methods: 1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were randomized 1:1 to Treatment as Usual (TAU) or the PGx guided-care arm. Patients and raters were blinded in both arms until after week 8. Primary outcomes were symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17 <7) at week 8. Medications in ‘use as directed’ or ‘use with caution’ PGx report categories were considered congruent, while medications in the ‘use with increased caution and more frequent monitoring’ category were incongruent. Patients on incongruent medications at baseline were analyzed separately.
Results: At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Conclusions: Combinatorial PGx testing improved response and remission rates for MDD compared to TAU, with improved outcomes when medication prescribing is congruent with PGx test results.