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Exposure to Antidepressant Medication and the Risk of Incident Dementia
Abstract
Objective To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia. Methods A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002-2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes. Results In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47. Conclusion In this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment.
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The study's findings are consistent with prior studies.
“Our findings are consistent with prior studies [12, 20-22, 27, 36].”
From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [21]
The evidence on the association between antidepressant use and dementia risk is inconsistent and remains uncertain.
“Previous studies have yielded inconsistent findings; while some suggest a protective effect [18, 19], others report a worsening effect [20-22], and others find no significant association [23, 24].”
From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [21]
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 [9]
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 [9]
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Metadata
- Authors
- Kodesh, A., Sandin, S., Reichenberg, A., Rotstein, A., Pedersen, N. L., Ericsson, M., Karlsson, I. K., Davidson, M., & Levine, S. Z.
- Affiliations
- Kupat Holim Meuchedet (IL)
- Karolinska Institutet (SE)
- Icahn School of Medicine at Mount Sinai (US)
- University of Haifa (IL)
- Tel Aviv University (IL)
- Corresponding author
- Levine, Stephen Z.
- ORCID
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 27
- Issue
- 11
- Pages
- 1177-1188
- ISSN
- 1064-7481 (ISSN-L)
- OpenAlex
- W2947875499
- Cited by
- 63
- References
- 40
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 11 · 2022: 7 · 2021: 7 · 2020: 15 · 2019: 3
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- 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
- antidepressants, dementia risk, incident dementia, antidepressant monotherapy, older adults, drug safety, depression, anxiety, adverse drug reactions
- MeSH terms
- Aged, Antidepressive Agents, Dementia, Depression, Female, Humans, Israel, Male, Middle Aged, Prospective Studies, Risk Factors, Proportional Hazards Models, Risk Assessment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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