Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Jul;106(1):271-279.
doi: 10.1177/13872877251340084. Epub 2025 May 7.

Differential effects of antidepressants on cognition in Alzheimer's disease with depression: A sub-group analysis of an open-label, observational study

Eduardo Cumbo  1 , Daniela Migliore  1
Affiliations
Randomized Controlled Trial

Differential effects of antidepressants on cognition in Alzheimer's disease with depression: A sub-group analysis of an open-label, observational study

Eduardo Cumbo et al. J Alzheimers Dis. 2025 Jul.

Abstract

BackgroundDepressive symptoms are common in Alzheimer's disease (AD), leading to an increasing use of antidepressants.ObjectiveTo compare the effects of vortioxetine with other conventional antidepressants on cognition in AD patients with depressive symptoms.MethodsThis analysis is a subgroup of a 12-month, prospective, randomized, open-label, parallel-group study involving 108 outpatients receiving either vortioxetine or escitalopram, paroxetine, or bupropion as part of routine care. Data were collected at baseline, 6 and 12 months. Cognitive symptoms were assessed using the Mini-Mental State Examination (MMSE), Attentive Matrices (AM), Coloured Progressive Matrices (CPR), and Digit Span; depressive symptoms using the Hamilton Depression Scale (HAM-D) and the Cornell Scale for Depression in Dementia (CSDD). Results for patients on vortioxetine were compared to those on other antidepressants.ResultsTotal scores on cognitive measures improved in all groups. Improvements versus baseline in MMSE, AM, and CPM were statistically significant in the vortioxetine group (p < 0.001), but not in the other antidepressant groups. Digit Span scores did not differ significantly from baseline. The between-group differences in MMSE, AM, and CPM changes were statistically significant in favor of vortioxetine (p < 0.05), while the Digit Span change showed a trend towards superiority with vortioxetine, but did not reach statistical significance. The between-group differences in HAM-D and CSDD changes were also statistically significant for vortioxetine (p < 0.05).ConclusionsVortioxetine was superior in improving both cognitive and depressive symptoms compared to other antidepressants. Larger studies which may also help to understand whether the beneficial effect observed with vortioxetine was a direct effect or mediated by its specific antidepressant efficacy are required.

Keywords: Alzheimer's disease; bupropion; cognitive impairment; depression; escitalopram; paroxetine; vortioxetine.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Eduardo Cumbo has participated in advisory boards and pharmaceutical industry-sponsored symposia for Pfizer, GSK, Eli Lilly, UCB Pharma, Neopharmed Gentili, Piam Pharma, Lundbeck and Novartis Pharma and has received compensation for speaker related activities from UCB Pharma, Pfizer, GSK, Neopharmed Gentili, Lundbeck and Novartis Pharma. Daniela Migliore declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Data availability statementThe data supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Publication types

LinkOut - more resources