Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder
Open accessAbstract
Background One third of patients with major depressive disorder (MDD) fail to respond to currently available antidepressant medications. Inflammation may contribute to treatment non-response through effects on neurotransmitter systems relevant to antidepressant efficacy. In post-hoc analyses, increased concentrations of inflammatory markers prior to treatment predict poor antidepressant response. However, limited data exists on whether depressed patients with multiple failed treatment trials in their current episode of depression exhibit increased inflammation.Methods Plasma concentrations of inflammatory markers were measured in unmedicated, medically stable patients with MDD (n = 98) and varying numbers of adequate antidepressant treatment trials in the current depressive episode as measured by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire. Covariates including age, sex, race, education, body mass index (BMI) and severity of depression were included in statistical models where indicated.Results A significant relationship was found between number of failed treatment trials and tumor necrosis factor (TNF), soluble TNF receptor 2 (sTNF-R2) and interleukin (IL)-6 (all p < 0.05 in multivariate analyses). Post hoc pairwise comparisons with correction for multiple testing revealed that patients with 3 or more failed trials in the current episode had significantly higher plasma TNF, sTNF-R2 and IL-6 compared to individuals with 0 or 1 trial (all p < 0.05). High sensitivity c-reactive protein was also associated with a greater number of treatment failures, but only in models with BMI excluded.Conclusions Measuring inflammatory markers and targeting inflammation or its downstream mediators may be relevant for depressed patients with multiple failed antidepressant treatment trials in their current depressive episode.
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For depression, low-grade inflammatory activity seems to be related to the failure of responding to pharmacological antidepressant treatments specifically.
“For depression, low-grade inflammatory activity seems to be related to the failure of responding to pharmacological antidepressant treatments specifically [27,28].”
From Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain (2022) · cites this paper as [27]
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Background
- Authors
- Haroon, E., Daguanno, A. W., Woolwine, B. J., Goldsmith, D. R., Baer, W. M., Wommack, E. C., Felger, J. C., & Miller, A. H.
- Affiliations
- Emory University (US)
- Corresponding author
- Miller, Andrew H.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 95
- Pages
- 43-49
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC6427066
- OpenAlex
- W2804087978
- Cited by
- 291
- References
- 49
- Citations by year
- 2026: 34 · 2025: 41 · 2024: 34 · 2023: 36 · 2022: 35 · 2021: 36 · 2020: 37 · 2019: 30 · 2018: 8
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Presbyterian Historical Society (KL2TR002381, UL1TR002378)
- National Institute of Mental Health (R01MH087604, R03MH100273)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, antidepressant treatment resistance, inflammatory markers, TNF-α, soluble TNF receptor 2, interleukin-6, C-reactive protein, plasma cytokines, inflammation and depression
- MeSH terms
- Adult, Antidepressive Agents, C-Reactive Protein, Major Depressive Disorder, Drug Tolerance, Female, Humans, Inflammation, Male, Middle Aged, Tumor Necrosis Factor-alpha, Biomarkers, Interleukin-6, Receptors, Tumor Necrosis Factor, Type II, Depressive Disorder, Treatment-Resistant
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