@article{ffe77b7796a0476299d3fce5267eb3c6,
title = "Higher S100B levels predict persistently elevated anhedonia with escitalopram monotherapy versus antidepressant combinations: Findings from CO-MED trial",
abstract = "Background: Elevated S100 calcium binding protein B (S100B) levels in systemic circulation may induce neuroinflammation and reflect greater blood–brain barrier (BBB) dysfunction. Neuroinflammation in patients with major depressive disorder (MDD), in turn, may reduce likelihood of improvement with serotonergic antidepressants. Methods: Levels of S100B were measured in plasma samples obtained prior to initiation of treatment with bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine in participants of Combining Medications to Enhance Depression Outcomes trial (n = 153). Depression severity was measured with 16-item Quick Inventory of Depressive Symptomatology Self-Report and anhedonia was measured with 3 items of 30-item Inventory of Depressive Symptomatology. Differential changes in depression severity and anhedonia over acute-phase (baseline, weeks 1, 2, 4, 6, 8, 10, and 12) in the three treatment arms were tested with logS100B-by-treatment-arm interaction in mixed model analyses after controlling for age, gender, and body mass index. Results: There was a significant logS100B-by-treatment-arm interaction for anhedonia (F = 3.21; df = 2, 142; p = 0.04) but not for overall depression severity (F = 1.99; df = 2, 142; p = 0.14). Higher logS100B levels were associated with smaller reductions in anhedonia (effect size = 0.67, p = 0.047) in escitalopram monotherapy but not in the other two arms. Correlation coefficients of anhedonia severity averaged over acute-phase (including baseline) with baseline S100B levels were 0.57, −0.19, and 0.22 for escitalopram monotherapy, bupropion-plus-escitalopram and venlafaxine-plus-mirtazapine arms respectively. Conclusion: Higher baseline S100B levels in depressed patients resulted in poorer response to escitalopram monotherapy. Addition of bupropion, a dopaminergic antidepressant, partially mitigated this effect.",
keywords = "Anhedonia, Antidepressant response, Blood, Brain barrier, Bupropion, Dopamine, Moderator, S100B, SSRIs, Serotonin",
author = "Jha, {Manish K.} and Abu Minhajuddin and Bharathi Gadad and Fatt, {Cherise Chin} and Trivedi, {Madhukar H.}",
note = "Funding Information: The CO-MED trial was funded by National Institute of Mental Health under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (Principal Investigators, M.H. Trivedi, and A.J. Rush). This work was also supported in part through the Center for Depression Research and Clinical Care at UT Southwestern (Principal Investigator: Madhukar H. Trivedi, MD) and Hersh Foundation. The authors thank the clinical staff at each clinical site for their assistance with this project; all of the study participants; and Georganna Carlock, B.A. for administrative support. Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for CO-MED trial at no cost. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data. The authors would like to thank the Metabolic Phenotyping Core at UT Southwestern Medical Center at Dallas, Texas for performing the S100B ELISA assays for the proposed study. Funding Information: Conflicts of Interest: Minhajuddin, Chin Fatt, and Gadad have no conflicts to report. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development. Trivedi has served as an adviser or consultant for Abbott Laboratories, Abdi Ibrahim, Akzo (Organon Pharmaceuticals), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon, Cerecor, CME Institute of Physicians, Concert Pharmaceuticals, Eli Lilly, Evotec, Fabre Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, Janssen Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products, Sepracor, Shire Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories; he has received grants or research support from the Agency for Healthcare Research and Quality, Cyberonics, NARSAD, NIDA, and NIMH. Funding Information: Acknowledgments: This work was also supported in part through the Center for Depression Research and Clinical Care at UT Southwestern (Principal Investigator: Madhukar H. Trivedi, MD) and Hersh Foundation. The authors thank the clinical staff at each clinical site for their assistance with this project; all of the study participants; and Georganna Carlock, B.A. for administrative support. Forest Pharmaceuticals, GlaxoSmithKline, Organon, and Wyeth Pharmaceuticals provided medications for CO-MED trial at no cost. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NIMH had no role in the drafting or review of the manuscript or in the collection or analysis of the data. The authors would like to thank the Metabolic Phenotyping Core at UT Southwestern Medical Center at Dallas, Texas for performing the S100B ELISA assays for the proposed study. Funding Information: Funding: The CO-MED trial was funded by National Institute of Mental Health under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (Principal Investigators, M.H. Trivedi, and A.J. Rush). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2019",
month = dec,
doi = "10.3390/ph12040184",
language = "English (US)",
volume = "12",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",
}