# Evaluating the rational use of antidepressant in older patients: a comprehensive analysis of its association with cognitive impairment

**Authors:** María Gil-Peinado, Juan Pardo, Mar García-Zamora, Gonzalo Miguel Adsuar-Meseguer, José Sendra-Lillo, Lucrecia Moreno

PMC · DOI: 10.3389/fpsyt.2025.1624989 · Frontiers in Psychiatry · 2025-10-20

## TL;DR

This study examines how antidepressants affect cognitive health in older patients and highlights the need for careful management to avoid worsening cognitive decline.

## Contribution

The study identifies drug-related problems and cognitive risks in antidepressant use among older patients and suggests alternatives like vortioxetine.

## Key findings

- Patients at risk of depression showed higher prevalence of cognitive impairment and greater use of antidepressants.
- Tricyclic antidepressants are linked to anticholinergic burden and potential cognitive decline.
- Vortioxetine is suggested as a safer alternative with potential cognitive benefits.

## Abstract

Dementia and Major Depressive Disorder (MDD) are on the rise globally, with depression frequently observed throughout the progression of dementia, potentially accelerating cognitive decline and diminishing quality of life. This study aims to explore the interplay between cognitive impairment (CI) and depression in patients undergoing antidepressant treatment, emphasizing drug-related problems (DRPs) and the Rational Use of Medicines (RUM).

Over a 6-year period, this cross-sectional study in Valencia, Spain, analyzed data from 777 patients aged over 50 concerned about their cognitive health. Cognitive status was assessed using three neuropsychological tests: Memory Impairment Screening (MIS), Verbal Semantic Fluency (VSF), and Pfeiffer’s Short Portable Mental State Questionnaire (SPMSQ). Various clinical and demographic variables associated with dementia were also evaluated.

The study identified a higher prevalence of CI among patients at risk of depression (GDS5 positive) compared to those without a depression risk. Patients with depression risk also demonstrated lower cognitive reserve, higher levels of loneliness, and increased use of antidepressants – notably tricyclic antidepressants (TCAs) – which are linked to anticholinergic burden and potential CI.

Despite their widespread use, antidepressants raise concerns regarding their efficacy and safety, particularly due to the risk of exacerbating CI. This study underscores the need for careful management of antidepressant therapy and suggests exploring alternatives such as vortioxetine, which may offer cognitive benefits. Enhanced interprofessional collaboration and regular cognitive evaluations are recommended to improve patient outcomes and ensure the rational use of antidepressants.

## Linked entities

- **Chemicals:** vortioxetine (PubChem CID 9966051)
- **Diseases:** dementia (MONDO:0001627), Major Depressive Disorder (MONDO:0002009)

## Full-text entities

- **Diseases:** depression (MESH:D003866), Dementia (MESH:D003704), MDD (MESH:D003865), Memory Impairment (MESH:D008569), CI (MESH:D003072)
- **Chemicals:** vortioxetine (MESH:D000078784)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12580571/full.md

## References

69 references — full list in the complete paper: https://tomesphere.com/paper/PMC12580571/full.md

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Source: https://tomesphere.com/paper/PMC12580571