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Increased Risk of Dementia in Patients with Antidepressants: A Meta-Analysis of Observational Studies
Open accessAbstract
Antidepressants are the most commonly and widely used medication for its effectiveness in the treatment of anxiety and depression. A few epidemiological studies have documented that antidepressant is associated with increased risk of dementia so far. Here, our aim is to assess the association between antidepressant use and risk of dementia in elderly patients. We searched articles through MEDLINE, EMBASE, Google, and Google Scholar from inception to December 1, 2017, that reported on the association between antidepressant use and dementia risk. Data were collected from each study independently, and study duplication was checked by at least three senior researchers based on a standardized protocol. Summary relative risk (RR) with 95% CI was calculated by using a random-effects model. We selected 9 out of 754 unique abstracts for full-text review using our predetermined selection criteria, and 5 out of these 9 studies, comprising 53,955 participants, met all of our inclusion criteria. The overall pooled RR of dementia was 1.75 (95% CI: 1.033–2.964) for SSRIs whereas the overall pooled RR of dementia was 2.131 (95% CI: 1.427–3.184) for tricyclic use. Also, MAOIs showed a high rate of increase with significant heterogeneity. Our findings indicate that antidepressant use is significantly associated with an increased risk of developing dementia. Therefore, we suggest physicians to carefully prescribe antidepressants, especially in elder patients. Additionally, treatment should be stopped if any symptoms related to dementia are to be noticed.
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In that meta-analysis, heterogeneity was extremely high, and one out of five included studies suggested that SSRI use was associated with a lower risk of dementia (RR 0.58, 95% CI 0.50-0.68).
“However, the heterogeneity in the meta-analysis was extremely high, and one out of five included studies suggested that SSRI use was associated with a lower risk of dementia (RR: 0.58, 95% CI: 0.50–0.68) [11].”
From Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study (2023) · cites this paper as [11]
Section 3.4 (page unavailable) reports five SSRI studies and extremely high heterogeneity (I² = 98.553). It does not report that one of those studies found a lower dementia risk with SSRI use, or give the claimed RR of 0.58 (95% CI 0.50–0.68); the pooled SSRI estimate instead indicates increased risk. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe lack of association in patients with underlying cognitive impairment is probably because clinicians are more concerned about the risk of dementia and thus prefer psychotherapy to SSRI/SNRI use.
“The association also did not exist in patients with underlying cognitive impairment, which is probably because clinicians are more concerned about the risk of dementia if patients have prior cognitive impairment, and thus psychotherapy is preferred to SSRI/SNRI use [11].”
From Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study (2023) · cites this paper as [11]
The Discussion (section 4.1; page unavailable) says the findings may make physicians more cautious about prescribing antidepressants, which supports the general concern about dementia risk. The Results (section 3.4; page unavailable) report an overall association, but the paper does not report a lack of association in patients with underlying cognitive impairment or say that clinicians prefer psychotherapy to SSRI/SNRI use for those patients. (LLM, conf=0.76)
Experimental — accuracy not yet measuredWang et al. found a higher dementia risk within 2 years of antidepressant use compared with psychotherapy in older adults with depression.
“Wang et al. [40] found a higher dementia risk within 2 years of antidepressant use compared with psychotherapy in older adults with 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 [40]
The Discussion (section 4.1) reports increased dementia risk among elderly antidepressant users compared with nonusers. It does not report a comparison with psychotherapy or a finding within two years; the Results (section 3.2) give follow-up periods of 3–11 years. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTwo 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 [37]
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Experimental — accuracy not yet measuredA meta-analysis including observational studies with at least a 1-year follow-up period showed that SSRI use was associated with an increased risk of dementia compared to no SSRI use, with a pooled risk ratio of 1.75 (95% CI 1.03-2.96).
“For example, a meta-analysis including observational studies with at least a 1-year follow-up period showed that SSRI use was associated with an increased risk of dementia compared to no SSRI use, with a pooled risk ratio (RR) of 1.75 (95% CI: 1.03–2.96).”
From Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study (2023) · cites this paper as [11]
Studies investigating the relationship between antidepressant use and AD/ADRD risk have yielded conflicting results.
“Studies looking into this question, however, have yielded conflicting results. 4-7”
From Antidepressant exposure and long‐term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder (2024) · cites this paper as [6]
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Metadata
- Authors
- Wang, Y.-C., Tai, P.-A., Poly, T. N., Islam, M. M., Yang, H.-C., Wu, C.-C., & Li, Y.-C. (.
- Affiliations
- Min Sheng General Hospital (TW)
- Tzu Chi University (TW)
- Taipei Medical University (TW)
- Wan Fang Hospital (TW)
- Corresponding author
- Li, Yu-Chuan (Jack)
- ORCID
- Venue
- Behavioural Neurology
- Publisher
- Wiley
- Published
- 2018-07-10
- Volume
- 2018
- Pages
- 1-8
- ISSN
- 0953-4180 (ISSN-L)
- 1875-8584
- PMC
- PMC6079596
- OpenAlex
- W2865610681
- Cited by
- 115
- References
- 5
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 19 · 2023: 11 · 2022: 12 · 2021: 7 · 2020: 40 · 2019: 9 · 2018: 1
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Behavioural Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministry of Education
- 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, dementia risk, elderly patients, selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, drug safety, depression treatment
- MeSH terms
- Antidepressive Agents, Dementia, Depression, Female, Humans, Male, Risk Factors, Selective Serotonin Reuptake Inhibitors
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