KORN KURATED RESEARCH

Exploring the Connection Between Antidepressants and Dementia

Recent research is shedding light on the potential cognitive risks associated with long-term use of antidepressants, particularly in older adults. Different classes of antidepressants have been linked to an increased risk of cognitive decline and dementia. This growing body of evidence is prompting a closer examination of the risk-benefit profile of these commonly prescribed medications.

The use of psychotropic medications for mental health tends more toward risk than benefit. This is why alternatives to pharmaceuticals should be tried first, except in the most extraordinary cases—to alleviate acute suffering or to keep someone safe from self-harm. The challenges of providing effective care and the overreliance on medications are directly linked to systemic failures within our healthcare system, including limited affordability and access to services, constraints on psychotherapy duration, inadequate housing and food insecurity, and insufficient programs addressing addiction and trauma, among other critical gaps. These social justice issues will take time to resolve. Nevertheless, these problems often drive the need for medication and the indiscriminate use of psychotropics by prescribers who feel they often have no other options.

People with depression, anxiety, and PTSD have often had unsatisfactory results with pharmaceutical use to manage symptoms or have experienced intolerable side effects. Often, they look to their therapist or physician for information about alternatives. However, they may not know where to start or what or who to believe.

The questions of the long-term safety of these medications have become even more urgent as we consider the connection between psychotropic medications and dementia. Several studies now suggest that long-term use of medications like benzodiazepines, antipsychotics, and antidepressants may contribute to cognitive decline in older adults. Our “collective” need for a quick fix may also be accelerating other forms of brain deterioration if we’re not careful. We need to expand access to integrative, nutritional, and trauma-informed alternatives.

The first study in this post, a cohort study, shows that antidepressant use in people with dementia is associated with faster cognitive decline. The effect is especially strong with SSRIs like escitalopram and citalopram, and higher doses are linked with greater risks of severe dementia, fractures, and mortality.

The second paper compares older adults with depression receiving SSRIs or SNRIs to those receiving psychotherapy and finds that antidepressant users have a higher risk of developing dementia within two years, even after adjusting for confounding factors.

The third article, a clinical review, also shows that many medications with anticholinergic activity—including some antidepressants—negatively impact cognitive function in older adults, increasing the risk of delirium, cognitive impairment, and dementia.

The fourth, a meta-analysis, examined six studies on antidepressant use and dementia risk in older adults. Despite some variability across the studies, the results suggest a significant link between antidepressant use and an increased risk of dementia. The researchers note that further research is needed to differentiate the effects of depression itself from the effects of antidepressants on dementia risk.
All of this raises concerns about polypharmacy. Medications stack up over time, and so do their cognitive effects. We need more systems in place to review medications, deprescribe thoughtfully, and guide patients through transitions—not only to prevent dementia but to improve their quality of life now.

Tags: Cognitive decline, dementia, psychotropic medications, antidepressants, anticholinergics

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Referenced Research Publications

BMC medicine
2025, February 25
DOI: 10.1186/s12916-025-03851-3

Antidepressant use and cognitive decline in patients with dementia: a national cohort study

Abstract

Background: Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia, fractures and death, depending on antidepressant class, drug, and dose.

Methods: This is a national cohort study. Patients with dementia registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem from May 1, 2007, until October 16, 2018, with at least one follow-up after dementia diagnosis, and who were new users of antidepressants, were included. Antidepressant use as a time varying exposure defined during the 6 months leading up to dementia diagnosis or each subsequent follow-up. We used linear mixed models to examine the association between antidepressant use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores. We used Cox proportional hazards models to calculate the hazard ratios for severe dementia (MMSE score < 10), fracture, and death. We compared antidepressant classes and drugs, and analyzed dose-response.

Results: We included 18740 patients (10 205 women [54.5%]; mean [SD] age, 78.2[7.4] years), of which 4271 (22.8%) received at least one prescription for an antidepressant. During follow-up, a total of 11912 prescriptions for antidepressants were issued, with selective serotonin reuptake inhibitors (SSRI) being the most common (64.8%). Antidepressant use was associated with faster cognitive decline (β (95% CI) = - 0.30(- 0.39, - 0.21) points/year), in particular sertraline (- 0.25(- 0.43, - 0.06) points/year), citalopram (- 0.41(- 0.55, - 0.27) points/year), escitalopram (- 0.76(- 1.09, - 0.44) points/year), and mirtazapine (- 0.19(- 0.34, - 0.04) points/year) compared with non-use. The association was stronger in patients with severe dementia (initial MMSE scores 0-9). Escitalopram showed a greater decline rate than sertraline. Compared with non-use, dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed.

Conclusions: In this cohort study, current antidepressant use was associated with faster cognitive decline; furthermore, higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality. These findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants use in patients with dementia.

Keywords: Antidepressants; Cognitive decline; Cohort; Dementia; Mortality.

© 2025. The Author(s).

Reference

Mo, M., Abzhandadze, T., Hoang, M. T., Sacuiu, S., Jurado, P. G., Pereira, J. B., Naia, L., Kele, J., Maioli, S., Xu, H., Eriksdotter, M., & Garcia-Ptacek, S. (2025). Antidepressant use and cognitive decline in patients with dementia: a national cohort study. BMC medicine, 23(1), 82. https://doi.org/10.1186/s12916-025-03851-3

BMC geriatrics
2023, December 08
DOI: 10.1186/s12877-023-04475-z

Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study

Abstract

Background: Prior studies suggested that antidepressant use is associated with an increased risk of dementia compared to no use, which is subject to confounding by indication. We aimed to compare the dementia risk among older adults with depression receiving first-line antidepressants (i.e., SSRI/SNRI) versus psychotherapy, which is also considered the first-line therapy for depression.

Methods: This retrospective cohort study was conducted using the US Medical Expenditure Panel Survey from 2010 to 2019. We included adults aged ≥ 50 years diagnosed with depression who initiated SSRI/SNRI or psychotherapy. We excluded patients with a dementia diagnosis before the first record of SSRI/SNRI use or psychotherapy. The exposure was the patient's receipt of SSRI/SNRI (identified from self-report questionnaires) or psychotherapy (identified from the Outpatient Visits or Office-Based Medical Provider Visits files). The outcome was a new diagnosis of dementia within 2 years (i.e., survey panel period) identified using ICD-9/ICD-10 codes from the Medical Conditions file. Using a multivariable logistic regression model, we reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We also conducted subgroup analyses by patient sex, age group, race/ethnicity, severity of depression, combined use of other non-SSRI/SNRI antidepressants, and presence of underlying cognitive impairment.

Results: Among 2,710 eligible patients (mean age = 61 ± 8, female = 69%, White = 84%), 89% used SSRIs/SNRIs, and 11% received psychotherapy. The SSRI/SNRI users had a higher crude incidence of dementia than the psychotherapy group (16.4% vs. 11.8%), with an aOR of 1.36 (95% CI = 1.06-1.74). Subgroup analyses yielded similar findings as the main analyses, except no significant association for patients who were aged < 65 years (1.23, 95% CI = 0.93-1.62), male (1.34, 95% CI = 0.95-1.90), Black (0.76, 95% CI = 0.48-1.19), had a higher PHQ-2 (1.39, 95% CI = 0.90-2.15), and had underlying cognitive impairment (1.06, 95% CI = 0.80-1.42). Conclusions: Our findings suggested that older adults with depression receiving SSRIs/SNRIs were associated with an increased dementia risk compared to those receiving psychotherapy.

Keywords: Antidepressants; Dementia; Depression; Older adults; Psychotherapy.

© 2023. The Author(s).

Reference

Wang, G. H., Chen, W. H., Chang, S. H., Zhang, T., Shao, H., Guo, J., & Lo-Ciganic, W. H. (2023). Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study. BMC geriatrics, 23(1), 825. https://doi.org/10.1186/s12877-023-04475-z

Clinical interventions in aging
2025, June 09
DOI: 10.2147/cia.s5358

The cognitive impact of anticholinergics: A clinical review

Abstract

Context:
The cognitive side effects of medications with anticholinergic activity have been documented among older adults in a variety of clinical settings. However, there has been no systematic confirmation that acute or chronic prescribing of such medications lead to transient or permanent adverse cognitive outcomes.

Objective:
Evaluate the existing evidence regarding the effects of anticholinergic medications on cognition in older adults.

Data sources:
We searched the MEDLINE, OVID, and CINAHL databases from January, 1966 to January, 2008 for eligible studies.

Study selection:
Studies were included if the anticholinergic activity was systematically measured and correlated with standard measurements of cognitive performance. Studies were excluded if they reported case studies, case series, editorials, and review articles.

Data extraction:
We extracted the method used to determine anticholinergic activity of medications and its association with cognitive outcomes.

Results:
Twenty-seven studies met our inclusion criteria. Serum anticholinergic assay was the main method used to determine anticholinergic activity. All but two studies found an association between the anticholinergic activity of medications and either delirium, cognitive impairment or dementia.

Conclusions:
Medications with anticholinergic activity negatively affect the cognitive performance of older adults. Recognizing the anticholinergic activity of certain medications may represent a potential tool to improve cognition.

Keywords: anticholinergic activity, cognitive impairment, delirium, elderly

Reference

Campbell, N., Boustani, M., Limbil, T., Ott, C., Fox, C., Maidment, I., Schubert, C. C., Munger, S., Fick, D., Miller, D., & Gulati, R. (2009). The cognitive impact of anticholinergics: a clinical review. Clinical interventions in aging, 4, 225–233. https://doi.org/10.2147/cia.s5358

Journal of clinical medicine
2023, October 03
DOI: 10.3390/jcm12196342

Association between Antidepressants and Dementia Risk in Older Adults with Depression: A Systematic Review and Meta-Analysis

Abstract

Depression, commonly treated with antidepressants, is associated with an increased risk of dementia, especially in older adults. However, the association between antidepressant use and dementia risk is unclear. We searched for randomized controlled trials and observational studies from PubMed, Embase, and Cochrane on 1 February 2022, restricting to full texts in English. Since dementia is a chronic disease requiring a long induction time, we restricted studies with ≥1 year follow-up. We extracted the relative risk (RR) adjusted for the most variables from each study and evaluated the heterogeneity using I square (I2). The protocol was registered in the PROSPERO International Register of Systematic Reviews (CRD42022338038). We included six articles in the systematic review, of which the sample size ranged from 716 to 141,740, and the median length of follow-up was 5 years. The pooled RR was 1.21 (95% CI = 1.12-1.29) with an I2 of 71%. Our findings suggest that antidepressant use was associated with an increased risk of dementia in older adults with depression, yet moderate to high heterogeneity existed across studies. Future work accounting for the depression progression is needed to differentiate the effect of depression and antidepressants on dementia risk.

Keywords: antidepressant; dementia; depression; meta-analysis; older adults; systemic review.

Reference

Wang, G. H., Li, P., Wang, Y., Guo, J., Wilson, D. L., & Lo-Ciganic, W. H. (2023). Association between Antidepressants and Dementia Risk in Older Adults with Depression: A Systematic Review and Meta-Analysis. Journal of clinical medicine, 12(19), 6342. https://doi.org/10.3390/jcm12196342