Yuen-Siang Ang1, Roselinde Kaiser2, Thilo Deckersbach3, Jorge Almeida4, Mary L Phillips5, Henry W Chase5, Christian A Webb1, Ramin Parsey6, Maurizio Fava7, Patrick McGrath8, Myrna Weissman8, Phil Adams8, Patricia Deldin9, Maria A Oquendo10, Melvin G McInnis9, Thomas Carmody11, Gerard Bruder8, Crystal M Cooper11, Cherise R Chin Fatt11, Madhukar H Trivedi11, Diego A Pizzagalli12. 1. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. 2. Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, Colorado. 3. Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts. 4. Department of Psychiatry, University of Texas at Austin, Dell Medical School, Austin, Texas. 5. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania. 6. Department of Psychiatry, Stony Brook University, Stony Brook, New York. 7. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts. 8. New York State Psychiatric Institute and Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, New York. 9. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan. 10. Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania. 11. Department of Psychiatry, University of Texas, Southwestern Medical Center, Dallas, Texas. 12. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts; Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts. Electronic address: dap@mclean.harvard.edu.
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.
RCT Entities:
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.
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