@article{b6ea3a3249b94e1f9bde4b6cb5d0af9f,
title = "Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression",
abstract = "We evaluated the clinical validity of a combinatorial pharmacogenomic test and single-gene Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines against patient outcomes and medication blood levels to assess their ability to inform prescribing in major depressive disorder (MDD). This is a secondary analysis of the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, which included patients with a diagnosis of MDD, and ≥1 prior medication failure. The ability to predict increased/decreased medication metabolism was validated against blood levels at screening (adjusted for age, sex, smoking status). The ability of predicted gene-drug interactions (pharmacogenomic test) or therapeutic recommendations (single-gene guidelines) to predict patient outcomes was validated against week 8 outcomes (17-item Hamilton Depression Rating Scale; symptom improvement, response, remission). Analyses were performed for patients taking any eligible medication (outcomes N=1,022, blood levels N=1,034) and the subset taking medications with single-gene guidelines (outcomes N=584, blood levels N=372). The combinatorial pharmacogenomic test was the only significant predictor of patient outcomes. Both the combinatorial pharmacogenomic test and single-gene guidelines were significant predictors of blood levels for all medications when evaluated separately; however, only the combinatorial pharmacogenomic test remained significant when both were included in the multivariate model. There were no substantial differences when all medications were evaluated or for the subset with single-gene guidelines. Overall, this evaluation of clinical validity demonstrates that the combinatorial pharmacogenomic test was a superior predictor of patient outcomes and medication blood levels when compared with guidelines based on individual genes.",
keywords = "CPIC guidelines, Clinical validity, Combinatorial pharmacogenomics, Depression, GeneSight, Medication blood levels, Pharmacokinetics",
author = "Rothschild, {Anthony J.} and Parikh, {Sagar V.} and Daniel Hain and Rebecca Law and Thase, {Michael E.} and Dunlop, {Boadie W.} and Charles DeBattista and Conway, {Charles R.} and Forester, {Brent P.} and Shelton, {Richard C.} and Matthew Macaluso and Krystal Brown and David Lewis and Alexander Gutin and Jablonski, {Michael R.} and Greden, {John F.}",
note = "Funding Information: Dr. Rothschild has received research support from Allergan, Assurex Health, Janssen, the National Institute of Mental Health, Otsuka, Eli-Lilly, Pfizer, and the Irving S. and Betty Brudnick Endowed Chair in Psychiatry. Dr. Rothschild is a consultant for GlaxoSmithKline, Janssen, Myriad Genetics, and SageTherapeutics. Dr. Rothschild receives royalties for the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT){\textregistered}; 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{\textregistered}. Dr. Parikh has received research funding from the Ontario Brain Institute, the Canadian Institutes of Health Research, the James and Ethel Flinn Foundation. Dr. Parikh has served as a consultant for Assurex Health (now Myriad Neuroscience). Dr. Parikh has received honoraria from Mensante Corporation, Takeda, and the Canadian Network for Mood and Anxiety Treatments (CANMAT). Dr. Parikh has equity in Mensante. Mr. Hain is employed by Myriad Neuroscience (formerly Assurex Health). Ms. Law is employed by Myriad Neuroscience (formerly Assurex Health). Dr. Thase has received research support from Assurex Health, Acadia, Agency for Healthcare Research and Quality, Alkermes, Avanir, Forest, Intracellular, Janssen, National Institute of Mental Health, Otsuka, Patient-Centered Outcomes Research Institute, and Takeda. Dr. Thase has served as a consultant for Acadia, Akilii, Alkermes, Allergan (Forest, Naurex), AstraZeneca, Cerecor, Eli Lilly, Fabre-Kramer, GersonLehrman Group, Guidepoint Global, Johnson & Johnson (Janssen, Ortho-McNeil), Lundbeck, MedAvante, Merck, Moksha8, Nestl{\'e} (PamLab), Novartis, Otsuka, Pfizer, Shire, Sunovion, Takeda. Dr. Thase receives royalties from American Psychiatric Press, Guilford Publications, Herald House, W.W. Norton & Company, Inc. Dr. Dunlop has received research support from Acadia,Aptinyx, Compass Pathways, NIMH, Sage,Assurex Health, Axsome, Janssen, and Takeda. Dr. Dunlop has served has a consultant for Aptinyx Greenwich Biosciences, Myriad Neuroscience (formerly Assurex Health), Otsuka, and Sophren Therapeutics. Dr. DeBattista has received research support from Assurex Health and Brain Resources. Dr. Conway has received research support from LivaNova and Bristol-Myers Squibb, the Stanley Medical Research Institute, the National Institute of Mental Health, NeoSyncInc, The Taylor Family Institute for Innovative Psychiatric Research, The August Busch IV Foundation, and the Barnes-Jewish Hospital Foundation. Dr. Conway has received speaking fees from Bristol-Myers Squibb and Otsuka Pharmaceuticals. Dr. Conway has served as a research design consultant for LivaNova. Dr. Conway is a part time employee of the John Cochran Veterans Administration Hospital in St. Louis. Dr. Forester has received research funding from the National Institutes of Health, Rogers Family Foundation, Spier Family Foundation, Assurex Health, Eli Lilly, and Biogen. Dr. Forester has served as a consultant for Biogen. Dr. Shelton has received research funding from Acadia Pharmaceuticals, Alkermes, Inc., Allergan, Assurex Health, Avanir Pharmaceuticals, Cerecor, Inc., Genomind, Intracellular Therapies, Janssen Pharmaceutica, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals. Dr. Shelton has served as a consultant for Acadia Pharmaceuticals, Allergan Inc., Cerecor, Inc., Janssen Pharmaceutica, Lundbeck A/S, Takeda Pharmaceuticals. Dr. Macalusco has conducted clinical trials research as principal investigator for Acadia, Alkermes, Allergan, Assurex Health, Eisai, Lundbeck, Janssen, Naurex/Aptinyx, and Neurim; all study contracts and payments were made to Kansas University Medical Cancer Research Institute. Dr. Brown is employed by Myriad Genetics. Dr. Lewis is employed by Myriad Neuroscience (formerly Assurex Health). Dr. Gutin is employed by Myriad Genetics. Dr. Jablonski is employed by Myriad Neuroscience (formerly Assurex Health). Dr. Greden has served as a scientific advisor for Janssen Pharmaceutical, Naurex (Allergan) Pharmaceutical, Cerecor Pharmaceutical, NeuralStem, Sage Therapeutics and Genomind. Dr. Greden received reimbursement as a speaker for Assurex Health in 2014. All work represented in this manuscript was done as an unpaid consultant to Myriad Neuroscience (formerly Assurex Health). Funding Information: Testing was provided in-kind by Assurex Health (now Myriad Neuroscience) as part of the original GUIDED trial. This study was supported by Myriad Neuroscience and its parent company, Myriad Genetics, Inc. Publisher Copyright: {\textcopyright} 2020",
year = "2021",
month = feb,
doi = "10.1016/j.psychres.2020.113649",
language = "English",
volume = "296",
journal = "Psychiatry Research",
issn = "0165-1781",
}