# Comparative effect of vortioxetine and sertraline on clinical and inflammatory profile in Parkinson’s disease with comorbid depression

**Authors:** Marika Alborghetti, Camilla Moliterni, Edoardo Bianchini, Domiziana Rinaldi, Daniela Caissutti, Antonella Capozzi, Fabiana Giada Radicati, Antonella Moschillo, Martina Marino, Isabella Berardelli, Marco Salvetti, Ferdinando Nicoletti, Roberta Misasi, Francesco Ernesto Pontieri

PMC · DOI: 10.3389/fnins.2026.1761550 · 2026-01-22

## TL;DR

This study compares vortioxetine and sertraline in Parkinson’s disease patients with depression, finding vortioxetine more effective in improving symptoms and immune function.

## Contribution

First evaluation of immunomodulatory effects of vortioxetine and sertraline in PD with comorbid depression.

## Key findings

- Vortioxetine showed greater improvement in cognitive function, anxiety, anhedonia, and apathy compared to sertraline.
- Vortioxetine had a restorative effect on CD40- and CD54-expressing dendritic cells, unlike sertraline.
- Both drugs reduced myeloid dendritic cells, but only vortioxetine improved their function.

## Abstract

Preclinical and clinical studies suggest that the multimodal antidepressant vortioxetine may offer a valuable therapeutic option in the treatment of depression associated with neurological disorders, including Parkinson’s disease (PD).

To compare the effect of vortioxetine and the SSRI sertraline in the treatment of PD and comorbid depression, placing emphasis on peripheral inflammation markers.

This is an observational longitudinal study. We have recruited 33 patients affected by PD with comorbid depression, evaluated for motor and non-motor symptoms, depression, and peripheral and soluble markers of inflammation at baseline and at the end of antidepressant treatment. Patients were divided into two groups treated with either vortioxetine (10–20 mg/day) or sertraline (50 mg/day) for 4 months. A group of 12 healthy controls was also used for comparative purposes.

At baseline PD patients showed a higher number of “classical” monocytes and a lower number of “non-classical” monocytes and myeloid dendritic cells (mDCs). The number and activity of DCs generated from isolated monocytes were also lower in PD patients. While both sertraline and vortioxetine treatment further reduced the number of mDCs, only vortioxetine had a restorative effect on CD40- and CD54-expressing DCs and their function. Both drugs display an antidepressant activity, but vortioxetine was superior to sertraline in improving cognitive function, anxiety, anhedonia, and apathy.

These data evaluate for the first time the immunomodulatory effects of two different treatments in PD patients with comorbid depression, highlighting the greater immunomodulatory capacity of vortioxetine.

## Linked entities

- **Proteins:** CD40 (CD40 molecule), ICAM1 (intercellular adhesion molecule 1)
- **Chemicals:** vortioxetine (PubChem CID 9966051), sertraline (PubChem CID 68617)
- **Diseases:** Parkinson’s disease (MONDO:0005180), depression (MONDO:0002050)

## Full-text entities

- **Genes:** CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}
- **Diseases:** anxiety (MESH:D001007), PD (MESH:D010300), inflammation (MESH:D007249), anhedonia (MESH:D059445), neurological disorders (MESH:D009461), depression (MESH:D003866)
- **Chemicals:** sertraline (MESH:D020280), vortioxetine (MESH:D000078784)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12874709/full.md

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Source: https://tomesphere.com/paper/PMC12874709