Abstract
Background: Standard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non–selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse. Methods: In a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline. Results: Greater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample. Conclusions: Pretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care.
Original language | English (US) |
---|---|
Pages (from-to) | 657-667 |
Number of pages | 11 |
Journal | Biological Psychiatry |
Volume | 88 |
Issue number | 8 |
DOIs | |
State | Published - Oct 15 2020 |
Keywords
- Antidepressant response
- Biomarkers
- Bupropion
- Frontostriatal connectivity
- Reward sensitivity
- Sertraline
ASJC Scopus subject areas
- Biological Psychiatry
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Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse. / Ang, Yuen Siang; Kaiser, Roselinde; Deckersbach, Thilo et al.
In: Biological Psychiatry, Vol. 88, No. 8, 15.10.2020, p. 657-667.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse
AU - Ang, Yuen Siang
AU - Kaiser, Roselinde
AU - Deckersbach, Thilo
AU - Almeida, Jorge
AU - Phillips, Mary L.
AU - Chase, Henry W.
AU - Webb, Christian A.
AU - Parsey, Ramin
AU - Fava, Maurizio
AU - McGrath, Patrick
AU - Weissman, Myrna
AU - Adams, Phil
AU - Deldin, Patricia
AU - Oquendo, Maria A.
AU - McInnis, Melvin G.
AU - Carmody, Thomas
AU - Bruder, Gerard
AU - Cooper Cortes, Crystal
AU - Chin Fatt, Cherise R.
AU - Trivedi, Madhukar H.
AU - Pizzagalli, Diego A.
N1 - Funding Information: The authors report the following financial disclosures, in the last 3 years (unless otherwise noted), for activities unrelated to the current research. MHT reports the following lifetime disclosures: research support from Agency for Healthcare Research and Quality, Cyberonics Inc., National Alliance for Research in Schizophrenia and Depression (NARSAD), NIMH, National Institute on Drug Abuse (NIDA), National Institute of Diabetes and Digestive and Kidney Diseases, and Johnson & Johnson; consulting and speaker fees from Abbott Laboratories Inc., Akzo (Organon Pharmaceuticals Inc.), Allergan Sales, Alkermes, AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb, Cephalon Inc., Cerecor, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals Inc., Forest Pharmaceuticals, GlaxoSmithKline, Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America Inc., MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. MF reports the following: research support from Acadia Pharmaceuticals, Allergan, Alkermes, Inc., Aptinyx, Avanir Pharmaceuticals Inc., Axsome, Benckiser Pharmaceuticals, Inc., BioClinica, Inc., Biogen, BioHaven, Cambridge Science Corporation, Cerecor, Gate Neurosciences, Inc., GenOmind, LLC, Gentelon, LLC, Happify, Johnson & Johnson, Lundbeck Inc., Marinus Pharmaceuticals, Methylation Sciences, Inc., Millennium Pharmaceutics, Inc. Minerva Neurosciences, Neuralstem, NeuroRX Inc., Novartis, Otsuka, Pfizer, Premiere Research International, Relmada Therapeutics Inc., Reckitt, Shenox Pharmaceuticals, Stanley Medical Research Institute, Taisho, Takeda, Vistagen, NIDA, NIH, NIMH, and PCORI; equity holdings in Compellis, Psy Therapeutics; patents for sequential parallel comparison design, licensed by MGH to Pharmaceutical Product Development, LLC (US_7840419, US_7647235, US_7983936, US_8145504, US_8145505); a patent application for a combination of ketamine plus scopolamine in MDD, licensed by MGH to Biohaven; patents for pharmacogenomics of depression treatment with folate (US_9546401, US_9540691); copyright for the MGH Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, Symptoms of Depression Questionnaire, and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte. Ltd. MLP reports consulting fees from Sunovion Pharmaceuticals. MW reports funding from NIMH, NARSAD, Sackler Foundation, and the Templeton Foundation; royalties from Oxford University Press, Perseus Press, American Psychiatric Association Press, and MultiHealth Systems. MAO reports funding from NIMH; royalties for commercial use of the Columbia Suicide Severity Rating Scale; her family owns stock in Bristol-Myers Squibb. MGM reports funding from NIMH; consulting fees from Janssen Pharmaceuticals and Otsuka Pharmaceuticals. TD reports funding from NIH, NIMH, Patient-Centered Outcomes Research Institute (PCORI), NARSAD, Tourette Syndrome Association, International OCD Foundation, Tufts University, Depression and Bipolar Alternative Treatment Foundation, Otsuka Pharmaceuticals, Cogito Inc., Sunovion, and Assurex Pharmaceuticals; honoraria, consultation fees, and/or royalties from MGH Psychiatry Academy, BrainCells Inc., Clintara, Systems Research and Applications Corporation, Boston University, Catalan Agency for Health Technology Assessment and Research, National Association of Social Workers Massachusetts, Massachusetts Medical Society, Tufts University, NIDA, NIMH, Oxford University Press, and Guilford Press; he has also participated in research funded by Assurex, Defense Advanced Research Projects Agency, NIH, NIMH, National Institute on Aging, Agency for Healthcare Research and Quality, PCORI, Janssen Pharmaceuticals, Forest Research Institute, Shire Development, Medtronic, Cyberonics, NorthStar, Takeda, and Sunovion. DAP: funding from NIMH, Brain and Behavior Research Foundation, Dana Foundation, and Millennium Pharmaceuticals; consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehreinger Ingelheim, Compass Pathway, Posit Science, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; one honorarium from Alkermes; he has a financial interest in BlackThorn Therapeutics, which has licensed the copyright to the probabilistic reward task through Harvard University; his interests were reviewed and are managed by McLean Hospital and Partners HealthCare in accordance with their conflict of interest policies. The other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: The EMBARC study was supported by the National Institute of Mental Health (NIMH) under Grant Nos. U01MH092221 (to MHT) and U01MH092250 (to PM, RP, and MW). Y-SA and DAP were supported by the A∗STAR National Science Scholarship and Grant No. R37 MH068376 , respectively. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center (coordinating principal investigator: MHT) and the Data Center at Columbia and Stony Brook Universities. Funding Information: The EMBARC study was supported by the National Institute of Mental Health (NIMH) under Grant Nos. U01MH092221 (to MHT) and U01MH092250 (to PM, RP, and MW). Y-SA and DAP were supported by the A?STAR National Science Scholarship and Grant No. R37 MH068376, respectively. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center (coordinating principal investigator: MHT) and the Data Center at Columbia and Stony Brook Universities. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). We are grateful to Daniel G. Dillon for his helpful comments on the manuscript. The authors report the following financial disclosures, in the last 3 years (unless otherwise noted), for activities unrelated to the current research. MHT reports the following lifetime disclosures: research support from Agency for Healthcare Research and Quality, Cyberonics Inc. National Alliance for Research in Schizophrenia and Depression (NARSAD), NIMH, National Institute on Drug Abuse (NIDA), National Institute of Diabetes and Digestive and Kidney Diseases, and Johnson & Johnson; consulting and speaker fees from Abbott Laboratories Inc. Akzo (Organon Pharmaceuticals Inc.), Allergan Sales, Alkermes, AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb, Cephalon Inc. Cerecor, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals Inc. Forest Pharmaceuticals, GlaxoSmithKline, Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America Inc. MSI Methylation Sciences Inc. Nestle Health Science-PamLab Inc. Naurex, Neuronetics, One Carbon Therapeutics Ltd. Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals Inc. Pfizer Inc. PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd. Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. MF reports the following: research support from Acadia Pharmaceuticals, Allergan, Alkermes, Inc. Aptinyx, Avanir Pharmaceuticals Inc. Axsome, Benckiser Pharmaceuticals, Inc. BioClinica, Inc. Biogen, BioHaven, Cambridge Science Corporation, Cerecor, Gate Neurosciences, Inc. GenOmind, LLC, Gentelon, LLC, Happify, Johnson & Johnson, Lundbeck Inc. Marinus Pharmaceuticals, Methylation Sciences, Inc. Millennium Pharmaceutics, Inc. Minerva Neurosciences, Neuralstem, NeuroRX Inc. Novartis, Otsuka, Pfizer, Premiere Research International, Relmada Therapeutics Inc. Reckitt, Shenox Pharmaceuticals, Stanley Medical Research Institute, Taisho, Takeda, Vistagen, NIDA, NIH, NIMH, and PCORI; equity holdings in Compellis, Psy Therapeutics; patents for sequential parallel comparison design, licensed by MGH to Pharmaceutical Product Development, LLC (US_7840419, US_7647235, US_7983936, US_8145504, US_8145505); a patent application for a combination of ketamine plus scopolamine in MDD, licensed by MGH to Biohaven; patents for pharmacogenomics of depression treatment with folate (US_9546401, US_9540691); copyright for the MGH Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, Symptoms of Depression Questionnaire, and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing Co. Pte. Ltd. MLP reports consulting fees from Sunovion Pharmaceuticals. MW reports funding from NIMH, NARSAD, Sackler Foundation, and the Templeton Foundation; royalties from Oxford University Press, Perseus Press, American Psychiatric Association Press, and MultiHealth Systems. MAO reports funding from NIMH; royalties for commercial use of the Columbia Suicide Severity Rating Scale; her family owns stock in Bristol-Myers Squibb. MGM reports funding from NIMH; consulting fees from Janssen Pharmaceuticals and Otsuka Pharmaceuticals. TD reports funding from NIH, NIMH, Patient-Centered Outcomes Research Institute (PCORI), NARSAD, Tourette Syndrome Association, International OCD Foundation, Tufts University, Depression and Bipolar Alternative Treatment Foundation, Otsuka Pharmaceuticals, Cogito Inc. Sunovion, and Assurex Pharmaceuticals; honoraria, consultation fees, and/or royalties from MGH Psychiatry Academy, BrainCells Inc. Clintara, Systems Research and Applications Corporation, Boston University, Catalan Agency for Health Technology Assessment and Research, National Association of Social Workers Massachusetts, Massachusetts Medical Society, Tufts University, NIDA, NIMH, Oxford University Press, and Guilford Press; he has also participated in research funded by Assurex, Defense Advanced Research Projects Agency, NIH, NIMH, National Institute on Aging, Agency for Healthcare Research and Quality, PCORI, Janssen Pharmaceuticals, Forest Research Institute, Shire Development, Medtronic, Cyberonics, NorthStar, Takeda, and Sunovion. DAP: funding from NIMH, Brain and Behavior Research Foundation, Dana Foundation, and Millennium Pharmaceuticals; consulting fees from Akili Interactive Labs, BlackThorn Therapeutics, Boehreinger Ingelheim, Compass Pathway, Posit Science, Otsuka Pharmaceuticals, and Takeda Pharmaceuticals; one honorarium from Alkermes; he has a financial interest in BlackThorn Therapeutics, which has licensed the copyright to the probabilistic reward task through Harvard University; his interests were reviewed and are managed by McLean Hospital and Partners HealthCare in accordance with their conflict of interest policies. The other authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC); https://clinicaltrials.gov/ct2/show/NCT01407094; NCT01407094. Publisher Copyright: © 2020 Society of Biological Psychiatry
PY - 2020/10/15
Y1 - 2020/10/15
N2 - Background: Standard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non–selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse. Methods: In a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline. Results: Greater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample. Conclusions: Pretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care.
AB - Background: Standard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non–selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse. Methods: In a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline. Results: Greater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample. Conclusions: Pretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care.
KW - Antidepressant response
KW - Biomarkers
KW - Bupropion
KW - Frontostriatal connectivity
KW - Reward sensitivity
KW - Sertraline
UR - http://www.scopus.com/inward/record.url?scp=85085688868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085688868&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2020.04.009
DO - 10.1016/j.biopsych.2020.04.009
M3 - Article
C2 - 32507389
AN - SCOPUS:85085688868
VL - 88
SP - 657
EP - 667
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 8
ER -