Decreased neutrophil-to-lymphocyte ratio predicted cognitive improvement in late-life depression treated with vortioxetine: findings from an eight-week randomized controlled trial
File(s)
Published version
Author(s)
Xue, Lingfeng
Lewis, Elin
Bocharova, Mariia
Young, Allan H
Aarsland, Dag
Type
Journal Article
Abstract
Background
Elevated neutrophil-to-lymphocyte ratio, a marker of inflammation, has been reported in adult and late-life depression. Vortioxetine has shown efficacy in treatment of late-life depression, yet little is known regarding its immunomodulatory role in clinical trials.
Methods
This is a post-hoc analysis of an eight-week randomized controlled trial. Depressed patients aged 65 or above were treated by vortioxetine, duloxetine or placebo. 321 patients that have taken blood tests at baseline and endpoint were included in the analysis. Neutrophil-to-lymphocyte ratio (NLR) was calculated using the absolute counts of each cell type. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery–Åsberg Depression Rating Scale (MADRS) and Geriatric Depression Scale (GDS).
Results
NLR levels decreased significantly in the entire analysis set (t(320) = 2.64, p = 0.008) and in the vortioxetine group (M = −0.186, t(105) = 2.070, p = 0.041, Cohen’s d = 0.20), but not in the two other groups. This decrease was not significantly different compared to placebo (F(1, 213) = 0.420, p = 0.517). Furthermore, larger NLR changes in vortioxetine arm predicted significant cognitive improvement (β = −4.03, p = 0.03), specifically regarding the DSST correct symbols (β = −1.97, p = 0.04) and RAVLT delayed recall (β = −1.87, p = 0.02) tasks. Additionally, decreased NLR significantly predicted reduced GDS score (β = 1.82, p = 0.02), yet not MADRS score.
Conclusion
Vortioxetine treatment was associated with decreased NLR levels in late-life depression, and reductions in NLR predicted improvements in cognitive function and depressive symptoms, suggesting a potential link between inflammation and clinical outcomes.
Elevated neutrophil-to-lymphocyte ratio, a marker of inflammation, has been reported in adult and late-life depression. Vortioxetine has shown efficacy in treatment of late-life depression, yet little is known regarding its immunomodulatory role in clinical trials.
Methods
This is a post-hoc analysis of an eight-week randomized controlled trial. Depressed patients aged 65 or above were treated by vortioxetine, duloxetine or placebo. 321 patients that have taken blood tests at baseline and endpoint were included in the analysis. Neutrophil-to-lymphocyte ratio (NLR) was calculated using the absolute counts of each cell type. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery–Åsberg Depression Rating Scale (MADRS) and Geriatric Depression Scale (GDS).
Results
NLR levels decreased significantly in the entire analysis set (t(320) = 2.64, p = 0.008) and in the vortioxetine group (M = −0.186, t(105) = 2.070, p = 0.041, Cohen’s d = 0.20), but not in the two other groups. This decrease was not significantly different compared to placebo (F(1, 213) = 0.420, p = 0.517). Furthermore, larger NLR changes in vortioxetine arm predicted significant cognitive improvement (β = −4.03, p = 0.03), specifically regarding the DSST correct symbols (β = −1.97, p = 0.04) and RAVLT delayed recall (β = −1.87, p = 0.02) tasks. Additionally, decreased NLR significantly predicted reduced GDS score (β = 1.82, p = 0.02), yet not MADRS score.
Conclusion
Vortioxetine treatment was associated with decreased NLR levels in late-life depression, and reductions in NLR predicted improvements in cognitive function and depressive symptoms, suggesting a potential link between inflammation and clinical outcomes.
Date Issued
2025-05-01
Date Acceptance
2025-01-31
Citation
Brain, Behavior, and Immunity, 2025, 126, pp.53-58
ISSN
0889-1591
Publisher
Elsevier BV
Start Page
53
End Page
58
Journal / Book Title
Brain, Behavior, and Immunity
Volume
126
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.bbi.2025.01.029
Subjects
Neutrophils
Lymphocytes
Humans
Sulfides
Piperazines
Antidepressive Agents
Treatment Outcome
Double-Blind Method
Depression
Cognition
Neuropsychological Tests
Aged
Aged, 80 and over
Female
Male
Duloxetine Hydrochloride
Vortioxetine
Publication Status
Published
Date Publish Online
2025-02-05