Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse

Yuen Siang Ang, Roselinde Kaiser, Thilo Deckersbach, Jorge Almeida, Mary L. Phillips, Henry W. Chase, Christian A. Webb, Ramin Parsey, Maurizio Fava, Patrick McGrath, Myrna Weissman, Phil Adams, Patricia Deldin, Maria A. Oquendo, Melvin G. McInnis, Thomas Carmody, Gerard Bruder, Crystal M. Cooper, Cherise R. Chin Fatt, Madhukar H. TrivediDiego A. Pizzagalli

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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 languageEnglish (US)
Pages (from-to)657-667
Number of pages11
JournalBiological Psychiatry
Issue number8
StatePublished - Oct 15 2020


  • Antidepressant response
  • Biomarkers
  • Bupropion
  • Frontostriatal connectivity
  • Reward sensitivity
  • Sertraline

ASJC Scopus subject areas

  • Biological Psychiatry


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