Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system
Abstract
Despite the evidence of an association between depression and increased inflammatory markers, still little is known in relation to the most severe cases of the disorder i.e., those who fail to respond to antidepressants. We have assessed the cytokine profile and cortisol levels in 21 healthy controls (HC) and 19 medicated patients with depression with treatment-resistance (TRD) moderately ill. As an initial exploratory analysis, we have also related cytokine profile to the patient's clinical treatment outcome after an inpatient admission. Cytokine profile was measured in the serum by the Cytokine Array I kit (Randox). Plasma cortisol was carried out using a commercially available for the IMMULITE system. When compared to healthy controls, depressed patients had higher levels of cortisol, IL-6, IL-10, but lower levels of IL-4 and VEGF. Our exploratory analysis showed subjects who did not go on to respond to the inpatient admission treatment package had lower levels of MCP-1, and a trend toward lower levels of VEGF. Taking together, these data suggest that lack of clinical therapeutic benefit of antidepressants is associated with overall activation of the inflammatory system.
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Inflammatory activity has been established as a factor in clinically depressed patients and highlighted as relevant in predicting or moderating treatment outcomes in chronic pain and depression.
“Inflammatory activity has been established as a factor in clinically depressed patients [24] and has recently been highlighted as relevant in the perspective of predicting or moderating treatment outcomes in chronic pain [25] and depression [26].”
From Baseline Pro-Inflammatory Cytokine Levels Moderate Psychological Inflexibility in Behavioral Treatment for Chronic Pain (2022) · cites this paper as [26]
A few studies suggest that peripheral immune activation may predict treatment non-response.
“In addition, a few studies suggest that peripheral immune activation may predict treatment non-response [12,14].”
Since the previous meta-analyses were published, new studies have appeared in the literature.
“Since these meta-analyses were published, new studies have appeared in the literature [12,13].”
Patients with the highest IL-6 levels are the least likely to respond to antidepressants.
“Patients with the highest IL-6 levels are also the least likely to respond to antidepressants (Carvalho et al., 2013).”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Carvalho et al., 2013
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“Inflammatory activity has been established as a factor in clinically depressed patients [24] and has recently been highlighted as relevant in the perspective of predicting or moderating treatment outcomes in chronic pain [25] and depression [26].”
Background
- Authors
- Carvalho, L. A., Torre, J. P., Papadopoulos, A. S., Poon, L., Juruena, M. F., Markopoulou, K., Cleare, A. J., & Pariante, C. M.
- Affiliations
- King's College London (GB)
- University College London (GB)
- Bethlem Royal Hospital (GB)
- Corresponding author
- Carvalho, L.A.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 148
- Issue
- 1
- Pages
- 136-140
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2033344078
- Cited by
- 167
- References
- 9
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 11 · 2023: 13 · 2022: 9 · 2021: 18 · 2020: 20 · 2019: 23 · 2018: 17 · 2017: 10 · 2016: 10 · 2015: 14 · 2014: 9 · 2013: 3
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Medical Research Council (MR/J002739/1)
- 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
- treatment-resistant depression, antidepressant response, cytokine profile, inflammatory markers, cortisol, interleukin-6, IL-10, IL-4, vascular endothelial growth factor, MCP-1, inpatient treatment outcomes
- MeSH terms
- Adult, Antidepressive Agents, Depression, Female, Humans, Hydrocortisone, Inflammation, Male, Middle Aged, Interleukin-4, Interleukin-6, Case-Control Studies, Cytokines, Interleukin-10, Treatment Outcome, Vascular Endothelial Growth Factor A
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