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J Psychiatr Res. 2019 Apr;111:59-67. doi: 10.1016/j.jpsychires.2019.01.003. Epub 2019 Jan 4.

Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: A large, patient- and rater-blinded, randomized, controlled study.

Author information

1
University of Michigan Department of Psychiatry and Comprehensive Depression Center 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA. Electronic address: gredenj@med.umich.edu.
2
University of Michigan Department of Psychiatry and Comprehensive Depression Center 4250 Plymouth Rd, Ann Arbor, MI, 48109, USA.
3
University of Massachusetts Medical School and UMass Memorial Healthcare, 55 N Lake Ave, Worcester, MA, 01655, USA.
4
Perelman School of Medicine of the University of Pennsylvania and the Corporal Michael Crescenz VAMC, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
5
Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, 12 Executive Park Dr NE #200, Atlanta, GA, 30329, USA.
6
Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, 401 Quarry Rd, Stanford, CA, 94305, USA.
7
Washington University School of Medicine, Department of Psychiatry, The John Cochran Veteran's Administration Hospital, 660 S Euclid Ave, St. Louis, MO, 63110, USA.
8
McLean Hospital, Division of Geriatric Psychiatry, Harvard Medical School, 115 Mill St, Belmont, MA, 02478, USA.
9
Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, 1800 Orleans St, Baltimore, MD, 21287, USA.
10
The University of Alabama at Birmingham, Department of Psychiatry and School of Medicine, 1720 2nd Ave S, Birmingham, AL, USA.
11
University of Kansas School of Medicine-Wichita, Department of Psychiatry and Behavioral Sciences, 1010 N Kansas St, Wichita, KS, 67214, USA.
12
Assurex Health, Inc., 6960 Cintas Blvd, Mason, OH, 45040, USA.
13
Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT, 84108, USA.
14
Assurex Health, Inc., 6960 Cintas Blvd, Mason, OH, 45040, USA; Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT, 84108, USA.

Abstract

Current prescribing practices for major depressive disorder (MDD) produce limited treatment success. Although pharmacogenomics may improve outcomes by identifying genetically inappropriate medications, studies to date were limited in scope. Outpatients (N = 1167) diagnosed with MDD and with a patient- or clinician-reported inadequate response to at least one antidepressant were enrolled in the Genomics Used to Improve DEpression Decisions (GUIDED) trial - a rater- and patient-blind randomized controlled trial. Patients were randomized to treatment as usual (TAU) or a pharmacogenomics-guided intervention arm in which clinicians had access to a pharmacogenomic test report to inform medication selections (guided-care). Medications were considered congruent ('use as directed' or 'use with caution' test categories) or incongruent ('use with increased caution and with more frequent monitoring' test category) with test results. Unblinding occurred after week 8. Primary outcome was symptom improvement [change in 17-item Hamilton Depression Rating Scale (HAM-D17)] at week 8; secondary outcomes were response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. At week 8, symptom improvement for guided-care was not significantly different than TAU (27.2% versus 24.4%, p = 0.107); however, improvements in response (26.0% versus 19.9%, p = 0.013) and remission (15.3% versus 10.1%, p = 0.007) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%, p = 0.002), response (28.5% versus 16.7%, p = 0.036), and remission (21.5% versus 8.5%, p = 0.007) compared to those remaining incongruent. Pharmacogenomic testing did not significantly improve mean symptoms but did significantly improve response and remission rates for difficult-to-treat depression patients over standard of care (ClinicalTrials.gov NCT02109939).

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