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Cited by 105Dementia and Cognitive Impairment ResearchTreatment of Major DepressionPharmaceutical Practices and Patient Outcomes

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The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: A systematic review and meta-analysis: M oraros et al.

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Moraros, John, Nwankwo, Chijioke, Patten, Scott B., Mousseau, Darrell D.·2017·Depression and Anxiety
DOI 10.1002/da.22584PMC PMC5347943
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Abstract

OBJECTIVE: To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). METHOD: We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model. RESULTS: Five articles were selected from an initial pool of 4,123 articles. Use of antidepressant drugs was associated with a significant twofold increase in the odds of some form of cognitive impairment or dementia (OR = 2.17). Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia. Studies that included participants with an average age equal to or greater than 65 years showed an increased odds of some form of cognitive impairment with antidepressant drug usage (OR = 1.65), whereas those with participants less than age 65 revealed an even stronger association (OR = 3.25). CONCLUSIONS: Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65. This association may arise due to confounding by depression or depression severity. However, biological mechanisms potentially linking antidepressant exposure to dementia have been described, so an etiological effect of antidepressants is possible. With this confirmation that an association exists, clarification of underlying etiologic pathways requires urgent attention.

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  • Two meta-analyses reported that antidepressant use increases dementia risk in elderly populations compared with nonusers, though high heterogeneity among included studies was noted, particularly regarding adjustments for confounders such as depression.

    “two meta-analyses reported that antidepressant use increases dementia risk in elderly populations compared with nonusers [37, 38], though high heterogeneity among included studies was noted, particularly regarding adjustments for confounders such as depression.”

    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 [38]

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  • Approximately 50% of antidepressants are prescribed for other conditions, such as off-label indications for schizophrenia, insomnia, or incontinence.

    “It has been reported that approximately 50% of antidepressants are prescribed for other conditions (such as off-label indications for prescription e.g. schizophrenia, insomnia or incontinence) [11].”

    From Understanding the Association Between Antidepressants and the Risk of Being Diagnosed with Dementia in Older People: A Self-Controlled Case Series Study (2020) · cites this paper as [11]

    The Introduction (page unavailable) says almost half of antidepressant prescriptions are for off-label indications and lists insomnia as an example. It lists anxiety and pain, however, not the citing sentence’s examples of schizophrenia and incontinence. (LLM, conf=0.88)

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Metadata

Authors
Moraros, J., Nwankwo, C., Patten, S. B., & Mousseau, D. D.
Affiliations
  • University of Saskatchewan (CA)
  • University of Calgary (CA)
Corresponding author
Mousseau, Darrell D.
ORCID
Venue
Depression and Anxiety
Publisher
Wiley
Published
2016-12-28
Volume
34
Issue
3
Pages
217-226
ISSN
1091-4269 (ISSN-L)
DOI
10.1002/da.22584
PMC
PMC5347943
OpenAlex
W2565406142
Cited by
105
References
9
Citations by year
2026: 6 · 2025: 3 · 2024: 13 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 18 · 2019: 8 · 2018: 18 · 2017: 5
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Depression and Anxiety (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Alzheimer Society of Saskatchewan
  • Saskatchewan Health Research Foundation (2015-2020)
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
antidepressants, cognitive impairment, dementia, Alzheimer's disease, drug safety, age as confounder, depression, antidepressant exposure
MeSH terms
Aged, Alzheimer Disease, Antidepressive Agents, Humans, Cognitive Dysfunction

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