Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial

Arun K Tiwari; Clement C Zai; C Anthony Altar; Julie-Anne Tanner; Paige E Davies; Paul Traxler; James Li; Elizabeth S Cogan; Matthew T Kucera; Ana Gugila; Nicole Braganza; Heather Emmerson; Gwyneth Zai; Daniel J Müller; Robert Levitan; Stefan Kloiber; Zafiris J Daskalakis; Benicio N Frey; James M Bowen; Jean-Eric Tarride; Richard Tytus; Ranjith Chandrasena; Nicholas Voudouris; Valerie H Taylor; Raymond Tempier; Verinder Sharma; Akshya Vasudev; Peter Dzongowski; Lew Pliamm; Todd Greenspoon; Bryan M Dechairo; James L Kennedy

doi:10.1038/s41398-022-01847-8

Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial

Transl Psychiatry. 2022 Mar 14;12(1):101. doi: 10.1038/s41398-022-01847-8.

Authors

Arun K Tiwari^#^{1

2}, Clement C Zai^#^{1

2

3

4}, C Anthony Altar⁵, Julie-Anne Tanner⁶, Paige E Davies⁶, Paul Traxler⁶, James Li⁶, Elizabeth S Cogan⁷, Matthew T Kucera⁷, Ana Gugila⁶, Nicole Braganza^{1

2}, Heather Emmerson^{1

2}, Gwyneth Zai^{1

2

3}, Daniel J Müller^{1

2

3}, Robert Levitan^{1

2

3}, Stefan Kloiber^{2

3

8}, Zafiris J Daskalakis⁹, Benicio N Frey^{10

11}, James M Bowen^{12

13

14}, Jean-Eric Tarride^{15

16

17}, Richard Tytus¹⁸, Ranjith Chandrasena¹⁹, Nicholas Voudouris²⁰, Valerie H Taylor²¹, Raymond Tempier^{22

23}, Verinder Sharma²⁴, Akshya Vasudev^{25

26}, Peter Dzongowski²⁷, Lew Pliamm²⁸, Todd Greenspoon²⁹, Bryan M Dechairo⁷, James L Kennedy^{30

31

32}

Affiliations

¹ Tanenbaum Centre for Pharmacogenetics, Neurogenetics Section, Molecular Brain Sciences Research Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
² Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³ Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
⁴ Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁵ Splice Therapeutics, 20271 Goldenrod Lane, Lab 2071, Germantown, MD, 20876, USA.
⁶ Myriad Neuroscience, Mason, OH, USA.
⁷ Myriad Genetics, Salt Lake City, UT, USA.
⁸ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
⁹ Department of Psychiatry, UC San Diego, San Diego, CA, USA.
¹⁰ Mood Disorders Treatment and Research Centre and Women's Health Concerns Clinic, St Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
¹¹ Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
¹² Department of Health Research Methods, Evidence and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Canada.
¹³ Program for Health System and Technology Evaluation, Ted Rogers Centre for Heart Research at Peter Munk Cardiac Centre, Toronto General Hospital Research Institute (TGHRI), Hamilton, Canada.
¹⁴ Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network (UHN), Hamilton, Canada.
¹⁵ Department of Health Research Methods, Evidence, and Impact (HEI), Faculty of Health Science, McMaster University, Hamilton, ON, Canada.
¹⁶ Programs for Assessment of Technology in Health (PATH), The Research Institute of St. Joe's Hamilton, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
¹⁷ Center for Health Economics and Policy Analysis (CHEPA), McMaster University, Hamilton, Canada.
¹⁸ Family Medicine, McMaster University, Hamilton, ON, Canada.
¹⁹ Chatham-Kent Health Alliance, Chatham, ON, Canada.
²⁰ Thornhill Medical Center, Toronto, ON, Canada.
²¹ Department of Psychiatry, University of Calgary, Hotchkiss Brain Institute, an Institute of the Cumming School of Medicine, Calgary, AB, Canada.
²² Hôpital Montfort, Ottawa, ON, Canada.
²³ Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada.
²⁴ Department of Psychiatry, Western University, London, ON, Canada.
²⁵ Department of Psychiatry, Geriatric Psychiatry and Neurosciences, Western University, London, ON, Canada.
²⁶ Integrative Psychiatry Lab, Parkwood Institute of Mental Health, London, ON, Canada.
²⁷ Milestone Research, London, ON, Canada.
²⁸ Canadian Phase Onward Inc., Polyclinic Family and Specialty Medicine Facility, Polyclinic Family Health Group, Toronto, ON, Canada.
²⁹ Hamilton Community Health Centre, Hamilton, ON, Canada.
³⁰ Tanenbaum Centre for Pharmacogenetics, Neurogenetics Section, Molecular Brain Sciences Research Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. jim.kennedy@camh.ca.
³¹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada. jim.kennedy@camh.ca.
³² Institute of Medical Science, University of Toronto, Toronto, ON, Canada. jim.kennedy@camh.ca.

^# Contributed equally.

Abstract

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. ("GUIDED"), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian "GAPP-MDD" RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antidepressive Agents / therapeutic use
Canada
Depression
Depressive Disorder, Major* / chemically induced
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Major* / genetics
Humans
Pharmacogenomic Testing*
Treatment Outcome

Substances

Antidepressive Agents

Associated data

ClinicalTrials.gov/NCT02466477