@article{b845094627004ee2b919249f6e68422f,
title = "Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection",
abstract = "Background: Interleukin 17 (IL-17) is produced by highly inflammatory Th17 cells and has been implicated in pathophysiology of depression. IL-17 putatively disrupts the blood brain barrier and affects dopamine synthesis whereas dopamine has been shown to decrease Th17 cell-mediated immune response. Nevertheless, whether IL-17 can predict differential treatment outcome with antidepressants modulating dopaminergic transmission is unknown. Methods: IL-17 and other T cell and non-T cell markers (Th1, Th2 and non-T cell markers) were measured with the Bioplex Pro{\texttrademark} human cytokine 27-plex kit in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants who provided baseline plasma and were treated with either bupropion plus escitalopram (bupropion-SSRI), escitalopram plus placebo (SSRI monotherapy), or venlafaxine plus mirtazapine (n = 166). Differential changes in symptom severity and side-effects based on levels of IL-17 and other T and non-T cell markers were tested using a treatment-arm-by-biomarker interaction in separate repeated measures mixed model analyses. Subsequent analyses stratified by treatment arm were conducted for those markers with a significant interaction. Results: There was a significant treatment-arm-by-IL-17 interaction for depression severity (p = 0.037) but not for side-effects (p = 0.28). Higher baseline IL-17 level was associated with greater reduction in depression severity (effect size = 0.78, p = 0.008) in the bupropion-SSRI but not the other two treatment arms. Other T and non-T cell markers were not associated with differential treatment outcomes. Conclusion: Higher baseline levels of IL-17 are selectively associated with greater symptomatic reduction in depressed patients treated with bupropion-SSRI combination.",
keywords = "Antidepressant, Bupropion, Dopamine, Inflammation, Interleukin 17, Moderator, T cells",
author = "Jha, {Manish K.} and Abu Minhajuddin and Gadad, {Bharathi S.} and Greer, {Tracy L.} and Mayes, {Taryn L.} and Trivedi, {Madhukar H.}",
note = "Funding Information: Drs. Jha, Minhajuddin, and Gadad as well as Ms. Mayes have no potential conflicts of interest. Dr. Greer has received research funding from NARSAD and honoraria and/or consultant fees from H. Lundbeck A/S and Takeda Pharmaceuticals International, Inc. Dr. Trivedi, is or has been an advisor/consultant and received fee from: Alkermes Inc., Allergan, Arcadia Pharmaceuticals Inc., AstraZeneca, Brintellix, BMS, Cerecor, Eli Lilly & Company, Forest Pharmaceuticals, Global Medical Education Inc., Health Research Associates, Johnson & Johnson, Lundbeck, Medscape, MSI Methylation Sciences Inc., Merck, Naurex Inc., Nestle Health Science – Pamlab Inc., One Carbon Therapeutics, Otsuka America Pharmaceuticals Inc., PamLab, Pfizer Inc., Roche, SHIRE Development, and Takeda Pharmaceuticals Inc. In addition, he has received grants/research support from: National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Drug Abuse, Agency for Healthcare Research and Quality, and Johnson & Johnson. Previous presentation: The findings of this report were presented at the 2016 Annual Meeting of Society of Biological Psychiatry. Funding Information: CO-MED trial was funded by NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (principal investigators, A.J. Rush and M.H. Trivedi). 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 . 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. Funding Information: CO-MED trial was funded by NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (principal investigators, A.J. Rush and M.H. Trivedi). 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. 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. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = nov,
doi = "10.1016/j.bbi.2017.07.005",
language = "English (US)",
volume = "66",
pages = "103--110",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",
}