Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: novel T cell biomarker for antidepressant medication selection
Open accessAbstract
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™ 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.
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IL-17A has been identified as a potential biomarker for forecasting responses to specific antidepressants.
“IL-17A has been identified as a potential biomarker for forecasting responses to specific antidepressants”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [63]
IL-17A levels predict treatment response to certain antidepressants.
“IL-17A levels predicts treatment response to certain antidepressants (Jha et al., 2017)”
From Distinct characteristics of hippocampal pathogenic th17 cells in a mouse model of depression (2018) · cites this paper as Jha et al., 2017
Jha et al. found that higher baseline levels of IL-17 were associated with greater symptomatic reduction in depressed patients treated with a bupropion-SSRI combination.
“For example, Jha et al. (210) found that higher baseline levels of IL-17 were associated with greater symptomatic reduction in depressed patients treated with a bupropion-SSRI combination.”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [210]
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Self-citationTh17-cells in depression: Implication in multiple sclerosis
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Self-citationDepression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD
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“IL-17A has been identified as a potential biomarker for forecasting responses to specific antidepressants [63].”
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- Authors
- Jha, M. K., Minhajuddin, A., Gadad, B. S., Greer, T. L., Mayes, T. L., & Trivedi, M. H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Trivedi, Madhukar H.
- ORCID
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 66
- Pages
- 103-110
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC5699207
- OpenAlex
- W2724318939
- Cited by
- 79
- References
- 56
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 13 · 2020: 9 · 2019: 11 · 2018: 10 · 2017: 2
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIMH
- UT Southwestern
- Hersh Foundation
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- IL-17, depression, antidepressant response, bupropion, escitalopram, venlafaxine, mirtazapine, Th17 cells, depression severity, antidepressant side effects
- MeSH terms
- Serotonin and Noradrenaline Reuptake Inhibitors, Venlafaxine Hydrochloride, Mirtazapine, Adult, Antidepressive Agents, Antidepressive Agents, Tricyclic, Depressive Disorder, Major, Major Depressive Disorder, Drug Therapy, Combination, Female, Humans, Inflammation, Male, Mianserin, Middle Aged, Psychiatric Status Rating Scales, Severity of Illness Index, T-Lymphocytes, Citalopram, Biomarkers, Bupropion, Selective Serotonin Reuptake Inhibitors, Antidepressive Agents, Second-Generation, Interleukin-17
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