Antidepressants and dementia
Abstract
Background It has been suggested that antidepressants may have neuroprotective abilities but it has newer been investigated lately whether treatment with antidepressants reduces the risk of dementia. Method Linkage of registers of all prescribed antidepressants and diagnoses of dementia in Denmark during a period from 1995 to 2005. Results Persons who purchased antidepressants once (N=687,552) had an increased rate of dementia compared to persons unexposed to antidepressants (N=779,831). Nevertheless, the rate of dementia changed over time; thus during the initial prescription periods the rate increased with the number of prescriptions but continued long-term antidepressants treatment was associated with a reduction in the rate of dementia, however, not to the same level as the rate for the general population. This pattern was found for all classes of antidepressants (SSRIs, newer non-SSRI antidepressants and older antidepressants). All findings were replicated in sub-analyses with Alzheimer's disease as outcome. Limitations Methodological reasons for the findings cannot be excluded due to the non-randomized nature of data. Conclusions Continued long-term antidepressant treatment was associated with a reduced rate of dementia, however, not to the same level as the rate for the general population.
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SSRIs reduce risk of AD in depressed individuals.
“Several studies have found that SSRIs reduce risk of AD in depressed individuals.”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [47]
Chronic antidepressant use lowered the risk of AD toward that of the general population.
“A recent retrospective study of over 1.4 million people in Denmark over a 10-y period suggested that depressed individuals who were treated only once, or for only a short period, had a greater risk of AD than those who had chronic antidepressant use (47); chronic antidepressant use lowered the risk toward that of the general population.”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [47]
In a retrospective study of over 1.4 million people in Denmark over 10 y, depressed individuals treated only once or for a short period had a greater risk of AD than those with chronic antidepressant use.
“A recent retrospective study of over 1.4 million people in Denmark over a 10-y period suggested that depressed individuals who were treated only once, or for only a short period, had a greater risk of AD than those who had chronic antidepressant use (47); chronic antidepressant use lowered the risk toward that of the general population.”
From Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans (2011) · cites this paper as [47]
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“, 2014) and the long-term use of antidepressants, such as SSRI, seems to lower the elevated risk on developing dementia in depressed individuals (Kessing et al., 2009).”
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“Similarly, excluding the study with the largest sample size (Kessing et al., 2009), yielded a pooled estimate of OR = 1.”
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“In addition, studies have interestingly shown a possible link between long-term antidepressant use and an increased risk of developing AD, as well as an increased risk of developing AD in depressed individuals (Ownby et al., 2006; Kessing et al., 2009; Wang et al., 2018).”
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BackgroundREVIEW: Apathy Diagnosis, Assessment, and Treatment in Alzheimer's Disease
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“In their large Danish population-based cohort (Kessing et al., 2009), Kessing and colleagues found that, compared to subjects exposed to one prescription of SSRIs, there was an increased risk of developing AD in subjects exposed to two prescriptions of SSRIs [relative risk (RR) (95% CI) = 1.55…”
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“For example, in a 15-year prospective cohort study involving 1063 veterans without dementia and not using BZAs at baseline, both incident and ever use of BZAs during follow-up was associated with significantly increased risk of dementia HR = 1.60; (1.08–2.38) and HR = 1.55 (1.24–1.95), respectively.33 Similarly in a n…”
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“Antidepressant medications were also suggested to reduce dementia incidence in analyses from Kessing et al in datasets drawn from large Danish registries of prescription drugs.(43,44) Our sensitivity analyses did not show significant associations of SSRIs and SSRIs/ TCAs with time to MoCA decline.”
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“Interestingly, a continued long-term treatment with antidepressants reduces the risk to develop AD (Kessing et al., 2009).”
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“Interestingly, recent studies have found that SSRIs reduce the risk of AD in depressed individuals [24] and have a positive role in hindering the progression of AD and improving patients’ daily performance [8, 9, 25].”
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“During the last decade, based on their ability to exert neuroprotection, the use of antidepressants to reduce the risk to develop AD has been proposed (Kessing et al., 2009; Kessing, 2012; Yuste et al., 2015; Bartels et al., 2018).”
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“tion (and eventually on the prevention of dementia) has been poorly studied and clearly remains to be elucidated (Kessing et al., 2009).”
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“Another study found increased rates of dementia during the initial prescription periods and then reductions in the rate of dementia during continued long-term antidepressant treatment.(9) However, our meta-analysis demonstrates that fluoxetine treatment for 8–12 weeks is associated with improved MMSE performance (Fig.”
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“Of note, several studies indicate that antidepressant treatment can reduce mortality risk for late life depression (10, 11) and reduce risk of dementia (12, 13).”
BackgroundAntidepressants in Alzheimer’s Disease: A Focus on the Role of Mirtazapine
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“A retrospective study that evaluated the relationship between the risk of AD and the use of SSRIs in depressed patients, concluded that individuals who took these drugs chronically had a lower risk of developing AD, compared to patients who only took these drugs in a short period [53].”
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Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study
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“We did not observe a difference in risk between SSRI use (excluding paroxetine) and nonuse, which conflicts with previous reports of higher risk of dementia associated with SSRI use.(17,19,20,23,25,26) Of these previous studies, all but one(26) failed to account for depression as a possible symptom of undiagnosed deme…”
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“Retrospective cohort studies, however, reported that SSRI treatment reduces cognitive decline and rate of dementia, although not to the level of the general population [17, 18].”
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“Some reports have shown possible efficacy of antidepressants in dementia (Kessing et al., 2009; Nelson and Devanand, 2011), addiction (Cahill et al.”
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“European Neuropsychopharmaco evidence comes from the epidemiological studies on AD risk reduction by SSRI treatment (Kessing et al., 2009).”
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“clear association between the use of antidepressants and these adverse outcomes (sometimes occurring decades later) [45,46] may reflect confounding by indication, e.”
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“Antidepressants prescribed for depressive disorder may have neuroprotective abilities [22,23] and patients may profit from psychotherapy before potential cognitive disturbances may occur during the long-term course of illness [24].”
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Overview of the Gut–Brain Axis: From Gut to Brain and Back Again
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“Most of them have reported an increased risk of dementia (Kessing et al., 2009; Lee et al., 2016; Then et al., 2017), except for one, which enrolled patients with more severe depression (Kessing et al.”
BackgroundInfluentialHypnotics use but not insomnia increased the risk of dementia in traumatic brain injury patients.
Chiu, H.-Y., Lin, E.-Y., Wei, L., Lin, J.-H., Lee, H.-C., Fan, Y.-C., & Tsai, P.-S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.09.011 · Cited by 20 · see citing works
“Because the use of NSAIDs and antidepressants have been shown to be associated with the risk of dementia (Breitner et al., 2009; Kessing et al., 2009), we included these factors in the calculation of the propensity score, and we included the propensity score in the Cox proportional-hazards models to account for the di…”
MethodAntidepressant Exposure and Risk of Dementia in Older Adults with Major Depressive Disorder
Brodrick, J., & Mathys, M. L. (2016) · Journal of The American Geriatrics Society · doi:10.1111/jgs.14378 · Cited by 19
“Continued long-term antidepressant use was associated with a reduction in the rate of dementia but not to the same level as that of the general population.(14) A similar study of individuals with depression discharged from Danish psychiatric facilities concluded that long-term treatment with older antidepressants (mos…”
ResultMonoamine Oxidase-A Physically Interacts with Presenilin-1(M146V) in the Mouse Cortex
Wei, Z.-L., Gabriel, G. G., Rui, L., Cao, X., Pennington, P. R., Chlan‐Fourney, J., Nazarali, A., Baker, G., & Mousseau, D. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-111241 · Cited by 18 · see citing works
“Our data also suggest that pharmacological MAO-A inhibition could exert non-cognitive effects in certain patients predisposed to AD (could this be extrapolated to other monoamine-altering therapeutics?, see [115]).”
Depressive Symptoms in Clinical and Incipient Alzheimer's Disease
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“The use of SSRIs is associated with a decreased rate of dementia/AD development (115).”
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“This theory is supported by the results of a large Danish population-based study in which patients who received only one prescription of SSRI antidepressants had an increased rate of dementia compared to subjects unexposed to antidepressants, while continued long-term antidepressant treatment (six to nine prescription…”
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“, 2011), or all people who were prescribed these medications regardless of indication (Wang et al., 2016; Kessing et al., 2009).”
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“Moreover, this same allele has been associated with cognitive deficits in depressed individuals (Kalska et al., 2013) and in older adults (Garrett et al., 2015), and has been proposed as a risk factor for AD/dementia (Li et al., 1997; Oliveira et al., 1998), although a later study was unable to corroborate any associa…”
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“Similarly, data do suggest that maintenance antidepressants prescribed for unipolar depressive disorder may have neuroprotective abilities but this is not definitive either [58,59].”
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“2017) whereas others find that SSRI use is associated with increased risk of dementia (Kessing et al. 2009).”
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“Tricyclic antidepressants (TCA) may be associated with a reduced risk (11) or no risk of dementia (12) for depressed patients, whereas nonselective serotonin reuptake inhibitors (SSRIs) antidepressant drugs, including monoamine oxidase (MAO) inhibitors, and serotonin and noradrenaline reuptake inhibitors (SNRIs) have…”
BackgroundRelationship between depressive symptomatology and cognitive performance in older people
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BackgroundResult[Use of antidepressants in unipolar depression in the elderly].
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Depression, Dementia, and Pseudodementia
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“TCA is safer than SNRIs in terms of dementia or cognitive dysfunction [42-44,48,50].”
BackgroundTroubles affectifs et comorbidités neurologiques
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- Authors
- Kessing, L. V., Søndergård, L., Forman, J. L., & Andersen, P. K.
- Affiliations
- Copenhagen University Hospital (DK)
- Rigshospitalet (DK)
- University of Copenhagen (DK)
- Corresponding author
- Kessing, Lars Vedel
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 117
- Issue
- 1-2
- Pages
- 24-29
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2015172698
- Cited by
- 113
- References
- 27
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 12 · 2017: 5 · 2016: 9 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 8
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- antidepressants, dementia, Alzheimer's disease, long-term antidepressant treatment, neuroprotection, selective serotonin reuptake inhibitors, prescribing patterns, dementia risk
- MeSH terms
- Adult, Aged, Alzheimer Disease, Antidepressive Agents, Dementia, Denmark, Depressive Disorder, Female, Humans, Male, Middle Aged, Registries, Risk, Time, Comorbidity, Prevalence, Age Distribution
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