TY - JOUR
T1 - Combinatorial Pharmacogenomic Testing Improves Outcomes for Older Adults With Depression
AU - Forester, Brent P.
AU - Parikh, Sagar V.
AU - Weisenbach, Sara
AU - Ajilore, Olusola
AU - Vahia, Ipsit
AU - Rothschild, Anthony J.
AU - Thase, Michael E.
AU - Dunlop, Boadie W.
AU - DeBattista, Charles
AU - Conway, Charles R.
AU - Shelton, Richard C.
AU - Macaluso, Matthew
AU - Li, James
AU - Traxler, Paul
AU - Logan, Jennifer
AU - Brown, Lisa
AU - Dechairo, Bryan
AU - Greden, John F.
N1 - Funding Information:
This study was supported by Assurex Health, Inc . (now Myriad Neuroscience). Assurex Health provided testing in kind.
Funding Information:
The authors thank Michael R. Jablonski, PhD, Krystal Brown, PhD, and Danielle Fanslow, PhD, for valuable editorial contributions to the manuscript, and Brenda Rubalcaba for graphical assistance with figures. This study was supported by Assurex Health, Inc. (now Myriad Neuroscience). Assurex Health provided testing in kind. Dr. Forester has received grant support from the National Institute on Aging, the Spier Family Foundation, the Rogers Family Foundation, Eli Lilly and Company, and Biogen. He is a consultant for Eli Lilly and Company and Biogen. Dr. Parikh has received research funding from the Ontario Brain Institute, the Canadian Institutes of Health Research, the James and Ethel Flinn Foundation. He has served as a consultant for Assurex Health, Inc./Myriad Neuroscience and has received honoraria from Mensante Corporation, Takeda Pharmaceutical Company Limited, and the Canadian Network for Mood and Anxiety Treatments. Dr. Parikh holds equity in Mensante Corporation. Dr. Weisenbach has received grant support from the Brain& Behavior Research Foundation and National Institute of Mental Health. Dr. Rothschild has received grant or research support from Allergan, Janssen Pharmaceuticals, Inc. the National Institute of Mental Health, Takeda Pharmaceutical Company Limited, Eli Lilly and Company (medications for a National Institutes of Health-funded clinical trial), Pfizer Inc. (medications for a National Institutes of Health-funded clinical trial), and the Irving S. and Betty Brudnick Endowed Chair in Psychiatry at the University of Massachusetts Medical School. He is a consultant to Alkermes, GlaxoSmithKline plc, Sage Therapeutics, Inc. and Sanofi-Aventis LLC.He receives royalties for the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT)?; Clinical Manual for the Diagnosis and Treatment of Psychotic Depression, American Psychiatric Press, 2009; The Evidence-Based Guide to Antipsychotic Medications, American Psychiatric Press, 2010; The Evidence-Based Guide to Antidepressant Medications, American Psychiatric Press, 2012, and UpToDate?. Dr. Thase has received research support from Assurex Health, Inc. Acadia Pharmaceuticals, the Agency for Healthcare Research and Quality, Alkermes, AvanirPharmaceuticals, Inc. Forest Laboratories (Allergan), Intracellular, Janssen Pharmaceuticals, Inc. the National Institute of Mental Health, Otsuka Pharmaceuticals, Inc. the Patient-Centered Outcomes Research Institute, and Takeda Pharmaceutical Company Limited. He has served as a consultant for Acadia Pharmaceuticals, Akili Interactive Labs, Inc. Alkermes, Allergan (Forest Laboratories, Naurex, Inc.), AstraZeneca, Cerecor, Inc. Eli Lilly and Company, Fabre-Kramer Pharmaceuticals, Inc. Gerson Lehrman Group Inc. Guidepoint Global, LLC, Johnson & Johnson (Janssen Pharmaceuticals, Inc. Ortho-McNeil Pharmaceutical), Lundbeck, MedAvante-ProPhase, Inc. Merck & Co. Inc. Moksha8 Pharmaceuticals, Inc. Nestl? Health Science (PamLab), Novartis AG, Otsuka Pharmaceuticals, Inc. PfizerInc, Shire (Takeda Pharmaceutical Company Limited), Sunovion Pharmaceuticals Inc. and Takeda Pharmaceutical Company Limited. He receives royalties from American Psychiatric Association Publishing, Guilford Press, Herald Publishing House, and W.W. Norton & Company, Inc. Dr. Dunlop has received research support from Acadia, Assurex Health, Inc. Axsome Therapeutics, Inc. Janssen Pharmaceuticals, Inc. and Takeda Pharmaceutical Company Limited, and he has served as a consultant for Assurex Health, Inc. and Aptinyx Inc. Dr. DeBattista has received research support from Assurex Health, Inc. and Brain Resources (Posit Science). Dr. Conway has received research support from LivaNova PLC and Bristol-Myers Squibb Company, the Stanley Medical Research Institute, the National Institute of Mental Health, NeoSync, Inc. the Taylor Family Institute for Innovative Psychiatric Research, the August Busch IV Foundation, and The Foundation For Barnes-Jewish Hospital. He has received speaking fees from Bristol-Myers Squibb Company and Otsuka Pharmaceuticals, Inc. He has served as a research design consultant for LivaNova PLC. He is a part-time employee of the John Cochran Veterans Hospital in St. Louis, MO. Dr. Shelton has received research funding from Acadia Pharmaceuticals, Alkermes, Allergan, Assurex Health, Inc. Avanir Pharmaceuticals, Inc. Cerecor, Inc. Genomind, Intra-Cellular Therapies Inc., Inc. and Takeda Pharmaceutical Company Limited. He has served as a consultant for Acadia Pharmaceuticals, Allergan, Cerecor, Inc. Janssen Pharmaceutica, Lundbeck, and Takeda Pharmaceutical Company Limited. Dr. Macaluso has conducted clinical trials research as principal investigator for Acadia Pharmaceuticals, Alkermes, Allergan, Assurex Health, Inc. Eisai Co. Ltd. Lundbeck, Janssen Pharmaceuticals, Inc. Neurim Pharmaceuticals, Inc. Sage Therapeutics, Inc. and Suven Life Sciences Limited; all clinical trial and study were with payments made to Kansas University Medical Cancer Research Institute, a research institute affiliated with Kansas University School of Medicine-Wichita. Dr. Li is an employee of Myriad Genetics, Inc. and receives salary and stock options as compensation. Mr. Traxler is an employee of Myriad Genetics, Inc. and receives salary and stock options as compensation. Dr. Logan is an employee of Myriad Genetics, Inc. and receives salary and stock options as compensation. Dr. Brown is an employee of Assurex Health, Inc./Myriad Neuroscience and receives salary and stock options as compensation. Dr. Dechairo is an employee of Myriad Genetics, Inc. and receives salary and stock options as compensation. Dr. Greden has served as a scientific advisor for Janssen Pharmaceuticals, Inc. Naurex Inc. (Allergan), Cerecor, Inc.NeuralStem, Inc. Sage Therapeutics, Inc. and Genomind. He received reimbursement as a speaker for Assurex Health, Inc. in 2014 and has served as an unpaid consultant to Assurex Health, Inc./Myriad Neuroscience. For the remaining authors none were declared. Previous presentation: This work was accepted for presentation as a poster at the 2020 American Association of Geriatric Psychiatry Annual Meeting, March 13?16, 2020, in San Antonio, Texas.
Publisher Copyright:
© 2020 The Authors
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Late-life depression
KW - antidepressant
KW - clinical trial
KW - geriatric depression
KW - major depressive disorder
KW - medication selection
KW - pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=85086037415&partnerID=8YFLogxK
U2 - 10.1016/j.jagp.2020.05.005
DO - 10.1016/j.jagp.2020.05.005
M3 - Article
C2 - 32513518
AN - SCOPUS:85086037415
SN - 1064-7481
VL - 28
SP - 933
EP - 945
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 9
ER -