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Comparative Effectiveness of Second‐Generation Antidepressants in Reducing the Risk of Dementia in Elderly Nursing Home Residents with Depression
Abstract
Study Objective: Second‐generation antidepressants have been shown to improve cognition and depression symptomatology, which are the major risk factors for dementia; however, little is known about the comparative effectiveness of antidepressants in reducing the risk of dementia. Thus, the objective of this study was to evaluate the long‐term comparative effectiveness of different antidepressant classes in reducing the risk of dementia in elderly nursing home residents with depression. Design: Propensity score–adjusted retrospective cohort study. Data Source: Multistate Minimum Data Set–linked Medicare Parts A, B, and D data files. Patients: A total of 25,108 nursing home residents (65 years and older) with a diagnosis of depression and without a dementia diagnosis who were Medicare beneficiaries and new users of selective serotonin reuptake inhibitors (SSRI s; 19,952 [79.5%]), serotonin‐norepinephrine reuptake inhibitors (SNRI s; 2381 [9.5%]), or tetracyclic antidepressants (2775 [11.1%]) between 2007 and 2010. Measurements and Main Results: New users of SSRI s, SNRI s, and tetracyclics were followed over a 2‐year period for the occurrence of dementia. A Cox proportional hazards regression model was used to evaluate the comparative effectiveness of SNRI s and tetracyclics in reducing the risk of dementia, with the SSRI class used as the reference category after controlling for propensity scores and their interactions terms. The unadjusted incidence of dementia was 8.2% for SSRI users, 6.0% for SNRI users, and 7.2% for tetracyclic users. The propensity score–adjusted Cox model did not find any significant difference in the risk of dementia in elderly nursing home residents who used SNRI s (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.84–1.19) or tetracyclics (HR 1.01, 95% CI 0.87–1.17) compared with the SSRI users. Conclusion: This study did not find any significant differences in reducing the risk of dementia among the new users of second‐generation antidepressant classes. Further studies are needed to evaluate the profiles of second‐generation antidepressants on cognition in this vulnerable population.
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Prior studies have employed propensity score matching to control for confounding factors and strengthen causal inferences when analyzing large observational datasets.
“Prior studies have employed various methodological approaches, including propensity score matching, to control for confounding factors and strengthen causal inferences when analyzing large observational datasets [12, 30].”
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 [30]
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Chan, J. Y. C., Yiu, K. K. L., Kwok, T. C. Y., Wong, S. Y. S., & Tsoi, K. K. F. (2019) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2018.12.004 · Cited by 135
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Metadata
- Authors
- Bali, V., Holmes, H. M., Johnson, M. L., Chen, H., Fleming, M. L., & Aparasu, R. R.
- Affiliations
- Health Advocate Westlake Village California
- The University of Texas MD Anderson Cancer Center (US)
- Texas Medical Center (US)
- Corresponding author
- Aparasu, Rajender R.
- Venue
- Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
- Publisher
- Wiley
- Published
- 2016-01
- Volume
- 36
- Issue
- 1
- Pages
- 38-48
- ISSN
- 0277-0008 (ISSN-L)
- 1875-9114
- OpenAlex
- W2227031661
- Cited by
- 11
- References
- 8
- Citations by year
- 2026: 1 · 2024: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- dementia risk, second-generation antidepressants, nursing home residents, geriatric depression, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tetracyclic antidepressants, comparative effectiveness, cognitive decline, long-term antidepressant use, Medicare beneficiaries, propensity score matching, Minimum Data Set
- MeSH terms
- Aged, Aged, 80 and over, Dementia, Depression, Female, Humans, Male, Nursing Homes, Retrospective Studies, Treatment Outcome, Antidepressive Agents, Second-Generation, Propensity Score
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