Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study
Abstract
OBJECTIVES: To determine whether antidepressant use is associated with dementia risk. DESIGN: Prospective cohort study. SETTING: Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. PARTICIPANTS: Community‐dwelling individuals aged 65 and older without dementia and with 10 years or more of KPWA enrollment at baseline (N=3,059). MEASUREMENTS: Primary exposures were selective serotonin reuptake inhibitors (paroxetine vs other), tricyclic antidepressants, and serotonin antagonist and reuptake inhibitors. Using health plan pharmacy data, we calculated cumulative medication exposure, defined as total standardized daily doses (TSDDs), over rolling 10‐year windows. Exposure in the most recent year was excluded to avoid use related to prodromal symptoms. The Cognitive Abilities Screening Instrument was administered every 2 years; low scores triggered clinical evaluation and consensus diagnosis procedures. Dementia risk was estimated according to medication use using Cox proportional hazards models. RESULTS: During a mean follow‐up of 7.7 years, 775 participants (25%) developed dementia; 659 (22%) developed possible or probable Alzheimer's disease. Individual antidepressant classes were not associated with differences in dementia risk, although paroxetine use was associated with higher risk of dementia for all TSDD categories than no use (0–90 TSDDs: hazard ratio (HR)=1.69, 95% confidence interval (CI)=1.18–2.42; 91–365 TSDDs: HR=1.40, 95% CI=0.88–2.23; 366–1095 TSDDs: HR=2.13, 95% CI=1.32–3.43; ≥1095 TSDDs: HR=1.42, 95% CI=0.82–2.46). CONCLUSION: Most commonly prescribed nonanticholinergic depression medications used in late life do not appear to be associated with dementia risk. Paroxetine and other anticholinergic antidepressants may be exceptions in older individuals. Future studies are warranted to improve scientific understanding of potential associations in other settings and populations.
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Prior cohort studies on antidepressant use and dementia risk have produced contrasting results.
“Long-term observational data are needed, but cohort studies to date have produced contrasting results. While various studies observed increased risk of dementia in antidepressant users, 4,8-14 several others did not. 15-19”
From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [14]
Other studies did link antidepressant use to increased dementia risk.
“In contrast, other studies did link antidepressant use to increased dementia risk. 4,8-14”
From Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy (2024) · cites this paper as [14]
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- Authors
- Heath, L., Gray, S. L., Boudreau, D. M., Thummel, K., Edwards, K. L., Fullerton, S. M., Crane, P. K., & Larson, E. B.
- Affiliations
- University of Washington (US)
- Kaiser Permanente Washington Health Research Institute (US)
- University of California, Irvine (US)
- Corresponding author
- Boudreau, Denise M.
- ORCID
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2018-09-17
- Volume
- 66
- Issue
- 10
- Pages
- 1948-1955
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- OpenAlex
- W2891035315
- Cited by
- 41
- References
- 43
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 7 · 2019: 6
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging
- National Institutes of Health (U01AG006781)
- Center for Scientific Review
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- antidepressant use, dementia risk, paroxetine, selective serotonin reuptake inhibitors, tricyclic antidepressants, Alzheimer's disease, older adults, drug safety
- MeSH terms
- Aged, Aged, 80 and over, Antidepressive Agents, Dementia, Depression, Female, Humans, Male, Prospective Studies, Risk Factors, Time Factors, Washington, Proportional Hazards Models, Selective Serotonin Reuptake Inhibitors, Paroxetine, Cholinergic Antagonists, Independent Living
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