Browse by author
Lookup NU author(s): Dr Judith HarrisonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Alzheimer's Association. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. BACKGROUND: Depression has been suggested as a modifiable risk factor for dementia. However, the impact of depression treatments on dementia risk remains unclear. This study assesses the association between exposure to different antidepressants and psychotherapy, and the risk of dementia. METHOD: Using Akrivia Health's mental healthcare database (anonymised electronic health records for 5.1 million patients in the UK), we identified all patients with major depressive disorder diagnosed between January 2000 and September 2022, aged 40 or older at diagnosis, without co-morbid bipolar disorder and/or schizophrenia, and dementia-free two years post-depression diagnosis. Patients were categorised into eight groups based on treatment type: psychotherapy only, tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), serotonin and noradrenaline re-uptake inhibitors (SNRIs), other antidepressants, and combined pharmacotherapy (≥ 2 antidepressants), with untreated patients as reference. Cox proportional hazards regression models estimated hazard ratios (HR) for dementia, adjusted for age, gender, and ethnicity. RESULT: A total of 56,423 individuals were identified (6,904 developed dementia during follow-up, 59% female, mean[SD] age: 67.6 [10.7]). Compared to untreated patients, all patients treated with antidepressants, but not those treated with psychotherapy only, showed a significantly greater risk of dementia, especially MAOIs (HR=2.15,95% confidence interval [CI] 1.39-3.34) and TCAs (HR=1.82, 95% CI 1.52-2.18). TCAs conferred a significantly greater risk than SSRIs (HR=1.39, 95% CI 1.29-1.50). CONCLUSION: This study showed that antidepressants, especially MAOIs and TCAs, are linked to an increased risk of dementia. The increased risk may be due to anticholinergic effects of antidepressants as well as residual confounding due to depression severity. Further research is needed to understand the underlying mechanisms and help clinicians balance the benefits of depression treatment with the risk of dementia.
Author(s): Kontari P, Taquet M, Pettersson-Yeo W, Harrison JR, Todorovic A, Fell B
Publication type: Article
Publication status: Published
Journal: Alzheimer's & Dementia
Year: 2025
Volume: 21
Issue: S7
Online publication date: 23/12/2025
Acceptance date: 02/04/2018
Date deposited: 08/01/2026
ISSN (print): 1552-5260
ISSN (electronic): 1552-5279
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/alz70861_108228
DOI: 10.1002/alz70861_108228
PubMed id: 41434714
Notes: Supplement: Developing Topics
Altmetrics provided by Altmetric
