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Safety of Using a Combinatorial Pharmacogenomic Test for Patients with Major Depressive Disorder in the GUIDED trial

Published online by Cambridge University Press:  10 May 2021

Sagar V. Parikh
Affiliation:
University of Michigan, Comprehensive Depression Center and Department of Psychiatry, and National Network of Depression Centers, Ann Arbor, MI, USA
Gabriela K. Khazanov
Affiliation:
University of Pennsylvania, Perelman School of Medicine, and the Corporal Michael Crescenz VAMC, Philadelphia, PA, USA
Michael E. Thase
Affiliation:
University of Pennsylvania, Perelman School of Medicine, and the Corporal Michael Crescenz VAMC, Philadelphia, PA, USA
Anthony J. Rothschild
Affiliation:
University of Massachusetts Medical School and UMass Memorial Healthcare, Worcester, MA, USA
Boadie W. Dunlop
Affiliation:
Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA, USA
Charles DeBattista
Affiliation:
Stanford University School of Medicine, Stanford, CA, USA
Charles R. Conway
Affiliation:
Washington University School of Medicine, St. Louis, MO, USA
Brent P. Forester
Affiliation:
McLean Hospital, Belmont, MA, USA
Richard C. Shelton
Affiliation:
The University of Alabama at Birmingham, Birmingham, AL, USA
Matthew Macaluso
Affiliation:
University of Kansas School of Medicine-Wichita, Wichita, KS, USA
James Li
Affiliation:
Myriad Neuroscience, Mason, OH, USA
Kunbo Yu
Affiliation:
Myriad Neuroscience, Mason, OH, USA
Michael R. Jablonski
Affiliation:
Myriad Neuroscience, Mason, OH, USA
Stephanie Meek
Affiliation:
Myriad Genetics, Inc., Salt Lake City, UT, USA
John F. Greden
Affiliation:
University of Michigan, Comprehensive Depression Center and Department of Psychiatry, and National Network of Depression Centers, Ann Arbor, MI, USA
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Abstract

Background

Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).

Materials and Methods

Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.

Results

Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.

Conclusion

These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.

Funding

Myriad Neuroscience/Assurex Health

Type
Abstracts
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Footnotes

Presenting Author: Sagar V. Parikh

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