Does escitalopram reduce neurotoxicity in major depression?
Abstract
A pro-inflammatory state and a dysregulation in the tryptophan/kynurenine pathway have been documented in depression. This study examined whether treatment with the SSRI, escitalopram (ESC), could suppress inflammation and favorably shift metabolites of the kynurenine pathway in patients with major depressive disorder (MDD) within the utilized treatment period. Twenty seven healthy control subjects were included for comparison. Thirty patients were enrolled after completing baseline assessments. They received a 12-week ESC monotherapy. Twenty subjects were completers. Clinical assessments were carried out at each visit using the HAM-D, HAM-A, CGI and BDI rating scales. Blood samples were collected at each assessment and stored until analyzed. Cytokines were analyzed with Randox multiplex assay and tryptophan and kynurenine metabolites were analyzed using HPLC/GCMS. Baseline plasma concentrations of hsCRP, TNFα, IL6 and MCP-1 were significantly higher in patients compared to healthy controls. IL10 trended toward an increase. Baseline plasma IL1β correlated significantly with IL1α, and IL4. Patients showed significant improvement in all outcome measures with a high remission rate. Significant correlations were obtained between specific symptoms and certain biomarkers at baseline but these correlations must be viewed as very preliminary. During ESC treatment concentrations of inflammatory biomarkers did not change except for TNFα that trended lower. Metabolites and ratios of the tryptophan/kynurenine pathway showed reductions of the neurotoxic metabolites, 3-hydroxykynurenine and quinolinic acid, 3-hydroxykynurenine/kynurenine, quinolinic acid/tryptophan, kynurenic acid/quinolinic acid and quinolinic acid/3-hydroxykynurenine. The results indicate that ESC may exert its antidepressant effect in part through inhibition of synthesis of certain neurotoxic kynurenine metabolites and possibly also through reduction of the inflammatory response, although there was no concordance in the time course of changes between antidepressant efficacy and reversal of the pro-inflammatory status.
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The study did not measure neurotoxic kynurenine-pathway metabolites such as 3-hydroxykynurenine and quinolinic acid.
“Substances not measured in the present study are neurotoxic kynurenine-pathway metabolites such as 3-hydroxykynurenine and quinolinic acid that have been suggested to be important for further understanding of imbalance of tryptophan-kynurenine pathway in MDD (Dantzer et al., 2011;Halaris et al., 2015;Steiner et al., 2011).”
From Tryptophan-kynurenine and lipid related metabolites as blood biomarkers for first-episode drug-naïve patients with major depressive disorder: An exploratory pilot case-control study (2018) · cites this paper as Halaris et al., 2015
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Heart Rate Variability Predicts Treatment Outcome in Major Depression
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Murata, S., Castillo, M. F. R., Murphy, M. L. M., Schwarz, M., Moll, N., Martin, B., Weidinger, E., Leitner, B., Mueller, N., & Halaris, A. E. (2019) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2019.07.001 · Cited by 10 · see citing works
Changes in tryptophan breakdown associated with response to multimodal treatment in depression
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Interleukin-8 is a potential inflammation biomarker in major depressive disorder
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Cardiolipin Antibody: A Potential Biomarker for Depression
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Autonomic Measures in Differentiating Depressive Disorders: A Potential AID.
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- Authors
- Halaris, A., Myint, A.-M., Savant, V., Meresh, E., Lim, E., Guillemin, G., Hoppensteadt, D., Fareed, J., & Sinacore, J.
- Affiliations
- Loyola University Medical Center (US)
- Maastricht University (NL)
- UNSW Sydney (AU)
- Macquarie University (AU)
- Corresponding author
- Halaris, Angelos
- ORCID
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 66-67
- Pages
- 118-126
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2112726857
- Cited by
- 86
- References
- 42
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 9 · 2023: 5 · 2022: 12 · 2021: 8 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 8 · 2016: 5 · 2015: 3
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- 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
- escitalopram, major depressive disorder, neuroinflammation, kynurenine pathway, kynurenine metabolites, quinolinic acid, 3-hydroxykynurenine, cytokines, TNF-α, interleukin-6, C-reactive protein, antidepressant mechanism, inflammatory markers
- MeSH terms
- Adult, Major Depressive Disorder, Female, Follow-Up Studies, Humans, Interleukins, Kynurenine, Male, Psychiatric Status Rating Scales, Tryptophan, Citalopram, Biomarkers, Cytokines, Selective Serotonin Reuptake Inhibitors, Quinolinic Acid
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