TY - JOUR
T1 - Impact of pharmacogenomics on clinical outcomes for patients taking medications with gene-drug interactions in a randomized controlled trial
AU - Thase, Michael E.
AU - Parikh, Sagar V.
AU - Rothschild, Anthony J.
AU - Dunlop, Boadie W.
AU - DeBattista, Charles
AU - Conway, Charles R.
AU - Forester, Brent P.
AU - Mondimore, Francis M.
AU - Shelton, Richard C.
AU - Macaluso, Matthew
AU - Li, James
AU - Brown, Krystal
AU - Jablonski, Michael R.
AU - Greden, John F.
N1 - Funding Information:
Submitted: May 13, 2019; accepted October 10, 2019. Published online: October 31, 2019. Potential conflicts of interest: 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 (NIMH), Otsuka, Patient-Centered Outcomes Research Institute, and Takeda; has served as a consultant for Acadia, Akili, Alkermes, Allergan (Forest, Naurex), AstraZeneca, Cerecor, Eli Lilly, Fabre-Kramer, Gerson Lehrman Group, Guidepoint Global, Johnson & Johnson (Janssen, Ortho-McNeil), Lundbeck, MedAvante, Merck, Moksha8, Nestlé (PamLab), Novartis, Otsuka, Pfizer, Shire, Sunovion, and Takeda; and receives royalties from American Psychiatric Press, Guilford Publications, Herald House, and W.W. Norton & Company, Inc. Dr Parikh has received research funding from the Ontario Brain Institute, the Canadian Institutes of Health Research, and the James and Ethel Flinn Foundation; has served as a consultant for Assurex Health; has received honoraria from Mensante Corporation, Takeda, and the Canadian Network for Mood and Anxiety Treatments (CANMAT); and has equity in Mensante. Dr Rothschild has received research support from Allergan, AssureRx, Janssen, NIMH, Takeda, Eli Lilly, and Pfizer; has served as a consultant for Alkermes, Eli Lilly, GlaxoSmithKline, Myriad Genetics, Pfizer, SageTherapeutics, and Sanofi-Aventis; and 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 (Wolters Kluwer). Dr Dunlop has received research support from Acadia, Assurex Health, Axsome, Janssen, and Takeda and has served has a consultant for Assurex Health and Aptinyx. Dr DeBattista has received research support from Assurex Health and Brain Resources. Dr Conway has received research support from LivaNova, Bristol-Myers Squibb, the Stanley Medical Research Institute, NIMH, NeoSync Inc, The Taylor Family Institute for Innovative Psychiatric Research, The August Busch IV Foundation, and the Barnes-Jewish Hospital Foundation; has received speaking fees from Bristol-Myers Squibb and
Funding Information:
This study was supported by Assurex Health (now Myriad Neuroscience, Mason, Ohio). Assurex Health provided testing in kind.
Funding Information:
Otsuka; has served as a research design consultant for LivaNova; and is a part-time employee of the John Cochran Veterans Administration Hospital in St. Louis, Missouri. Dr Forester has received research funding from the National Institutes of Health, Rogers Family Foundation, Spier Family Foundation, Assurex Health, Eli Lilly, and Biogen and has served as a consultant for Biogen. Dr Mondimore has received research funding from Assurex Health. Dr Shelton has received research funding from Acadia, Alkermes, Allergan, Assurex Health, Avanir, Cerecor, Genomind, Intracellular Therapies, Janssen, Otsuka, and Takeda and has served as a consultant for Acadia, Allergan, Cerecor, Janssen, Lundbeck, and Takeda. Dr Macaluso 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. Drs Li and Jablonski are employed by Assurex Health (now Myriad Neuroscience). Dr Brown is employed by Myriad Genetics Inc. Dr Greden has served as a scientific advisor for Janssen, Naurex (Allergan), Cerecor, NeuralStem, Sage Therapeutics, and Genomind and received reimbursement as a speaker for Assurex Health in 2014; all work was done as an unpaid consultant to Assurex and Myriad. Funding/support: This study was supported by Assurex Health (now Myriad Neuroscience, Mason, Ohio). Assurex Health provided testing in kind. Role of the sponsor: Assurex Health (now Myriad Neuroscience, Mason, Ohio) provided testing and participated in the study design for the original trial. Authors who are employed by the sponsor participated in data analysis, data interpretation, and manuscript drafting as part of their roles as authors. Supplementary material: Available at PSYCHIATRIST.COM.
Publisher Copyright:
© 2019 Physicians Postgraduate Press, Inc.
PY - 2019
Y1 - 2019
N2 - Objective: The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. Methods: Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P=.069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. Results: Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P=.029; response: 27.0% versus 19.0%, P=.008; remission: 18.2% versus 10.7%, P=.003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P=.011 for symptom improvement, P=.011 for response, P=.008 for remission). Conclusions: By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure.
AB - Objective: The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. Methods: Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P=.069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. Results: Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P=.029; response: 27.0% versus 19.0%, P=.008; remission: 18.2% versus 10.7%, P=.003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P=.011 for symptom improvement, P=.011 for response, P=.008 for remission). Conclusions: By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure.
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U2 - 10.4088/JCP.19m12910
DO - 10.4088/JCP.19m12910
M3 - Article
C2 - 31721487
AN - SCOPUS:85074961245
SN - 0160-6689
VL - 80
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 6
M1 - 19m12910
ER -