Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial
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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.
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- Authors
- Ang, Y.-S., Bruder, G. E., Keilp, J. G., Rutherford, A., Alschuler, D. M., Pechtel, P., Webb, C. A., Carmody, T., Fava, M., Cusin, C., McGrath, P. J., Weissman, M., Parsey, R., Oquendo, M. A., McInnis, M. G., Cooper, C. M., Deldin, P., Trivedi, M. H., & Pizzagalli, D. A.
- Affiliations
- Harvard University (US)
- New York State Psychiatric Institute (US)
- McLean Hospital (US)
- The University of Texas Southwestern Medical Center (US)
- Massachusetts General Hospital (US)
- Stony Brook University (US)
- University of Michigan (US)
- Corresponding author
- Pizzagalli, Diego A.
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2020-11-20
- Volume
- 52
- Issue
- 13
- Pages
- 2441-2449
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC7613805
- OpenAlex
- W3103697121
- Cited by
- 12
- References
- 64
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust (209581, 209581/Z/17/Z)
- National Institute of Mental Health (U01MH092250, U01MH092221, R37MH068376)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, antidepressant response, bupropion, sertraline, neurocognitive predictors, reward responsiveness, cognitive control, verbal fluency, psychomotor speed, processing speed, treatment-resistant depression, placebo response, biosignatures
- MeSH terms
- Antidepressive Agents, Calcium Phosphates, Major Depressive Disorder, Depressive Disorder, Major, Double-Blind Method, Humans, Bupropion, Treatment Outcome, Sertraline
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