Decreased neutrophil-to-lymphocyte ratio predicted cognitive improvement in late-life depression treated with vortioxetine: Findings from an eight-week randomized controlled trial

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.