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Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial

Published online by Cambridge University Press:  20 November 2020

Yuen-Siang Ang ,
Gerard E. Bruder ,
John G. Keilp ,
Ashleigh Rutherford ,
Daniel M. Alschuler ,
Pia Pechtel ,
Christian A. Webb ,
Thomas Carmody ,
Maurizio Fava  and
Cristina Cusin
...Show all authors
Yuen-Siang Ang
Affiliation:
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA
Gerard E. Bruder
Affiliation:
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
John G. Keilp
Affiliation:
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
Ashleigh Rutherford
Affiliation:
Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA
Daniel M. Alschuler
Affiliation:
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
Pia Pechtel
Affiliation:
Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA
Christian A. Webb
Affiliation:
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA
Thomas Carmody
Affiliation:
Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, Texas, USA
Maurizio Fava
Affiliation:
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
Cristina Cusin
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
Patrick J. McGrath
Affiliation:
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
Myrna Weissman
Affiliation:
Department of Psychiatry, New York State Psychiatric Institute and Columbia University Vagelos College of Physicians and Surgeons, New York, USA
Ramin Parsey
Affiliation:
Department of Psychiatry, Stony Brook University, Stony Brook, New York, USA
Maria A. Oquendo
Affiliation:
Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
Melvin G. McInnis
Affiliation:
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA
Crystal M. Cooper
Affiliation:
Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, Texas, USA
Patricia Deldin
Affiliation:
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, USA
Madhukar H. Trivedi
Affiliation:
Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, Texas, USA
Diego A. Pizzagalli*
Affiliation:
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA McLean Imaging Center, McLean Hospital, Belmont, Massachusetts, USA
*
Author for correspondence: Diego A. Pizzagalli, E-mail: dap@mclean.harvard.edu
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Abstract

Background

Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.

Methods

In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.

Results

Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.

Conclusion

These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.

Keywords

Biomarkersbupropioncognitive controldepressionplacebo responsereward learningsertralinetreatment response
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 13 , October 2022 , pp. 2441 - 2449
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press.

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