Brent P Forester1, Sagar V Parikh2, Sara Weisenbach3, Olusola Ajilore4, Ipsit Vahia5, Anthony J Rothschild6, Michael E Thase7, Boadie W Dunlop8, Charles DeBattista9, Charles R Conway10, Richard C Shelton11, Matthew Macaluso12, James Li13, Paul Traxler13, Jennifer Logan14, Lisa Brown13, Bryan Dechairo14, John F Greden2. 1. Division of Geriatric Psychiatry (BPF, IV), McLean Hospital, Harvard Medical School, Belmont, MA. Electronic address: bforester@mclean.harvard.edu. 2. University of Michigan Comprehensive Depression Center and Department of Psychiatry (SVP, JFG), National Network of Depression Centers, Ann Arbor, MI. 3. Stony Brook University, Department of Psychiatry & Behavioral Health (SW), Stony Brook, NY. 4. University of Illinois at Chicago, School of Public Health/Psychiatric Institute (OJ), Chicago, IL. 5. Division of Geriatric Psychiatry (BPF, IV), McLean Hospital, Harvard Medical School, Belmont, MA. 6. University of Massachusetts Medical School and UMass Memorial Healthcare (AJR), Worcester, MA. 7. Perelman School of Medicine of the University of Pennsylvania, the Corporal Michael Crescenz VAMC (MET), Philadelphia, PA. 8. Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences (BWD), Atlanta, GA. 9. Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences (CDB), Stanford, CA. 10. Washington University School of Medicine, Department of Psychiatry, and the John Cochran Veteran's Administration Hospital (CRC), St. Louis, MO. 11. The University of Alabama at Birmingham, Department of Psychiatry and School of Medicine (RCS), Birmingham, AL. 12. University of Kansas School of Medicine-Wichita, Department of Psychiatry and Behavioral Sciences (MM), Wichita, KS. 13. Assurex Health, Inc./Myriad Neuroscience (PT, LB), Mason, OH. 14. Myriad Genetics, Inc. (JL, BD), Salt Lake City, UT.
Abstract
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 rateat 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 (χ2 = 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.
RCT Entities:
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 rateat 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 (χ2 = 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.
Authors: Victoria S Marshe; Malgorzata Maciukiewicz; Anne-Christin Hauschild; Farhana Islam; Li Qin; Arun K Tiwari; Etienne Sibille; Daniel M Blumberger; Jordan F Karp; Alastair J Flint; Gustavo Turecki; Raymond W Lam; Roumen V Milev; Benicio N Frey; Susan Rotzinger; Jane A Foster; Sidney H Kennedy; James L Kennedy; Benoit H Mulsant; Charles F Reynolds; Eric J Lenze; Daniel J Müller Journal: Transl Psychiatry Date: 2021-02-15 Impact factor: 6.222