OBJECTIVE: Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD).

DESIGN: Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms.

SETTING: Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites.

PARTICIPANTS: Adults age 65 years or older at baseline (n=206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode.

INTERVENTION: Combinatorial pharmacogenomic testing to inform medication selection (guided-care), compared with treatment as usual (TAU).

OUTCOMES: Mean percent symptom improvement, response rate, and remission rat eat week 8, measured using the 17-item Hamilton Depression Rating Scale; medication switching; and comorbidity moderator analysis.

RESULTS: At week 8, symptom improvement was not significantly different for guided-care than for TAU (=8.1%, t=1.64, df=187; p=0.102); however, guided-care showed significantly improved response (=13.6%, t=2.16, df=187; p=0.032) and remission (=12.7%, t=2.49, df=189; p=0.014) relative to TAU. By week 8, more than twice as many patients in guided-care than in TAU were on medications predicted to have no gene-drug interactions (chi(2)=19.3, df=2; p < 0.001). Outcomes in the guided-care arm showed consistent improvement through the end of the open-design 24-week trial, indicating durability of the effect. Differences in outcomes between arms were not significantly impacted by comorbidities.

CONCLUSIONS: Combinatorial pharmacogenomic test-informed medication selection improved outcomes over TAU among older adults with depression.