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Cited by 0Dementia and Cognitive Impairment ResearchPharmaceutical Practices and Patient OutcomesTreatment of Major Depression

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index; 36 of the 45 sources its claims cite were checked for support.

Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis

Open access
Amrein, Melanie A., Hengartner, Michael P., Näpflin, Markus, Farcher, Renato, Huber, Carola A.·2026·Drugs - Real World Outcomes
DOI 10.1007/s40801-026-00560-yPMC PMC13570850
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Abstract

BACKGROUND: Antidepressants are widely prescribed, with increasing use among older adults. However, evidence on their association with dementia remains inconsistent. OBJECTIVE: This study examines the association between long-term antidepressant use and dementia risk in older adults using a propensity score-matched design, with a separate analysis of long-term tricyclic antidepressant (TCAs) use, given their anticholinergic properties. METHODS: A retrospective cohort study was conducted using Swiss healthcare claims data (2013-2023) from older adults aged 65 years and above. Long-term antidepressant users (> 2 years) and long-term TCAs users were separately matched to nonusers using variable ratio propensity score matching. The primary outcome was incident dementia, defined by a recorded dementia diagnosis or antidementia drug prescription. Covariates were derived from inpatient and/or outpatient records, depending on the respective variable. RESULTS: A final sample of 19,155 long-term antidepressant users were compared with 20,648 propensity score matched nonusers. After adjusting for covariates, long-term antidepressant use was significantly associated with dementia (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.72-2.15, p < 0.001). Long-term TCAs users also had higher odds of developing dementia compared with nonusers (OR 1.73, 95% CI 1.33-2.25, p < 0.001). Sensitivity analyses largely confirmed these results: long-term antidepressant users had higher odds of developing dementia compared with short-term users (OR 1.23, 95% CI 1.11-1.35, p < 0.001), but for TCA, the difference between long-term and short-term users was not statistically significant (OR 1.25, 95% CI 0.99-1.57, p = 0.059). CONCLUSIONS: These findings suggest that long-term antidepressant and long-term TCAs use is associated with an increased risk of dementia in older adults, even after accounting for various comorbidities. This study adds to the ongoing debate on the link between antidepressants and dementia. Future research is needed to further clarify underlying mechanisms and guide clinical practice.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a Swiss healthcare claims cohort of adults aged ≥65, long-term antidepressant use (>2 years) was associated with higher odds of incident dementia than matched nonuse (OR 1.92, 95% CI 1.72–2.15). Long-term tricyclic antidepressant use was also associated with higher dementia odds (OR 1.73, 95% CI 1.33–2.25), though the long- versus short-term TCA comparison was not statistically significant.

Key findings

  • Long-term antidepressant users had 4.9% incident dementia vs 2.6% in propensity score-matched nonusers; adjusted OR 1.92 (95% CI 1.72–2.15, p < 0.001).
  • Long-term TCA users had 4.2% incident dementia vs 2.5% in matched nonusers; adjusted OR 1.73 (95% CI 1.33–2.25, p < 0.001).
  • In sensitivity analyses, long-term antidepressant users had higher dementia odds than short-term users (OR 1.23, 95% CI 1.11–1.35, p < 0.001), but for TCAs the long- vs short-term difference was not statistically significant (OR 1.25, 95% CI 0.99–1.57, p = 0.059).
  • Among long-term antidepressant users, 18.7% had at least one TCA prescription and 8.2% had only TCA prescriptions during the study period.

Methods

  • Retrospective cohort study using Swiss Helsana healthcare claims data from 1 January 2013 to 31 December 2023; population was adults aged ≥65 continuously enrolled, with a 1-year washout and exclusion of dementia diagnoses or antidementia prescriptions during washout/treatment.
  • Long-term antidepressant use was defined as prescriptions in ≥9 quarters during an 11-quarter treatment phase (>2 years, allowing up to 6-month interruption); long-term TCA use was analyzed separately.
  • Variable-ratio propensity score matching with nearest-neighbor algorithm (up to 12 controls per treated individual; mean matching ratio ≈3) and exact matching on key covariates; logistic regression on the matched sample estimated dementia odds, with robust standard errors and adjustment for matching covariates.

Limitations

  • Stated: observational design precludes causal inference and residual confounding may persist; lifestyle factors, genetic predisposition, and psychosocial variables were not accounted for.
  • Stated: dementia ascertainment may be incomplete because outpatient diagnoses were unavailable, inpatient diagnoses likely reflect later disease stages, and medication-based ascertainment may underrepresent subtypes such as frontotemporal dementia.
  • Stated: depression was identified using inpatient diagnoses only, likely capturing more severe cases and missing outpatient-treated individuals; protopathic and indication bias cannot be excluded.
  • Stated: restricting to continuously enrolled individuals created a survivor population by excluding those who died, potentially influencing outcomes and limiting generalizability.
  • Evident from text: the TCA long- vs short-term sensitivity analysis was underpowered, as the authors note the lack of statistical significance may be due to limited power in that subgroup.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/s40801-026-00560-y

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

36 of 45 cited sources checked · 21 supported · 1 flagged · accuracy not yet measured

  • Premisecitation
    § Key Points · p. 2

    Depression may represent an early symptom or prodrome of dementia in some individuals.

    “Depression may also even represent an early symptom or prodrome of dementia in some individuals, making it challenging to disentangle causality in the antidepressant-dementia relationship [27-29].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [27] Chan JYC, Yiu KKL, Kwok TCY, et al. Depression and antidepressants as potential risk factors in dementia: a systematic review and meta-analysis of 18 longitudinal studies. J Am Med Dir Assoc. 2019;20:279-286.e1. https://doi.org/10.1016/j.jamda.2018.12.004. source
    • cites [28] Pless A, Ware D, Saggu S, et al. Understanding neuropsychiatric symptoms in Alzheimer’s disease: challenges and advances in diagnosis and treatment. Front Neurosci. 2023;17:1263771. https://doi.org/10.3389/fnins.2023.1263771. source

      The Diagnosis and challenges section (page unavailable) says neuropsychiatric symptoms, including depression, can emerge quickly after an Alzheimer’s diagnosis. The Depression section discusses depression in diagnosed patients and its association with increased AD risk, but does not establish that depression is a prodrome preceding dementia. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [29] Wiels W, Baeken C, Engelborghs S. Depressive symptoms in the elderly-an early symptom of dementia? A systematic review. Front Pharmacol. 2020;11:34. https://doi.org/10.3389/fphar.2020.00034. source
  • Premisecitation
    § Key Points · p. 2

    Anticholinergic drugs block acetylcholine, a neurotransmitter essential for cognitive function.

    “Anticholinergic drugs block acetylcholine, a neurotransmitter essential for cognitive function, and have been associated with an increased risk of dementia in older adults [15, 31, 32].”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [15] Coupland CAC, Hill T, Dening T, et al. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179:1084–93. https://doi.org/10.1001/jamainternmed.2019.0677. source
    • cites [31] Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175:401–7. https://doi.org/10.1001/jamainternmed.2014.7663. source
    • cites [32] Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. https://doi.org/10.1136/bmj.k1315. source
  • Premisecitation
    § Key Points · p. 2

    Anticholinergic drugs have been associated with an increased risk of dementia in older adults.

    “Anticholinergic drugs block acetylcholine, a neurotransmitter essential for cognitive function, and have been associated with an increased risk of dementia in older adults [15, 31, 32].”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [15] Coupland CAC, Hill T, Dening T, et al. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179:1084–93. https://doi.org/10.1001/jamainternmed.2019.0677. source
    • cites [31] Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175:401–7. https://doi.org/10.1001/jamainternmed.2014.7663. source
    • cites [32] Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. https://doi.org/10.1136/bmj.k1315. source
  • Premisecitation
    § Key Points · p. 2

    Depression is a potential dementia risk factor.

    “depression itself is a potential dementia risk factor [24-26]”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [24] Ramos-Cejudo J, Corrigan JK, Zheng C, et al. Antidepressant exposure and long-term dementia risk in a nationwide retrospective study on US veterans with midlife major depressive disorder. Alzheimers Dement. 2024;20:4106–14. https://doi.org/10.1002/alz.13853. source
    • cites [25] Then C-K, Chi N-F, Chung K-H, et al. Risk analysis of use of different classes of antidepressants on subsequent dementia: a nationwide cohort study in Taiwan. PLoS ONE. 2017;12:e0175187. https://doi.org/10.1371/journal.pone.0175187. source
    • cites [26] Solomonov N, Alexopoulos GS. Do antidepressants increase the risk of dementia? Am J Geriatr Psychiatry. 2019;27:1189–91. https://doi.org/10.1016/j.jagp.2019.06.004. source
  • Interpretationcitation
    § 4 Discussion · p. 8

    Long-term antidepressant use may directly influence neurodegenerative processes through alterations in brain chemistry or plasticity.

    “Long-term antidepressant use may directly influence neurodegenerative processes through alterations in brain chemistry or plasticity [45, 46]”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [45] Willard SL, Uberseder B, Clark A, et al. Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates. Neuropharmacology. 2015;99:369–78. https://doi.org/10.1016/j.neuropharm.2015.06.011. source

      The Results (section 3.2) report a change in a marker of central serotonergic function, and the Discussion reports that long-term sertraline treatment changed brain-region volumes in adult female monkeys. The Introduction describes neurogenesis and synaptic connectivity as potential mechanisms. The paper does not establish that these changes affect neurodegenerative processes or that the proposed plasticity mechanisms caused the observed volume changes. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [46] Kobayashi K, Ikeda Y, Sakai A, et al. Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci USA. 2010;107:8434–9. https://doi.org/10.1073/pnas.0912690107. source

      The Results and Discussion report that chronic fluoxetine altered serotonin-related signaling, neuronal maturation, and synaptic plasticity in adult mice. They do not establish that these changes influence neurodegenerative processes; that part of the citing sentence goes beyond the paper. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Probably not a substantial claim. 21
  • It may state two separate claims as one. 17
  • The quote only partly states this claim. 2

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation
    § 4 Discussion · p. 7

    Other studies have found no association between antidepressant use and dementia risk.

    “other studies have found no association between antidepressant use and dementia risk [18, 19, 23, 41].”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [18] Cortes-Flores H, Torrandell-Haro G, Brinton RD. Association between CNS-active drugs and risk of Alzheimer’s and age-related neurodegenerative diseases. Front Psychiatry. 2024;15:1358568. https://doi.org/10.3389/fpsyt.2024.1358568. source

      The Results report a statistically significant association between antidepressant use and lower Alzheimer’s disease risk, rather than no association. The Discussion likewise says antidepressant classes were associated with a significant risk reduction. The passages do not report other studies finding no association. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [19] Jacob L, Bohlken J, Kostev K. Risk of dementia in German patients treated with antidepressants in general or psychiatric practices. Int J Clin Pharmacol Ther. 2017;55:322–8. https://doi.org/10.5414/CP202754. source
    • cites [23] vom Hofe I, Stricker BH, Vernooij MW, et al. Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy. Alzheimers Dement. 2024;20:3378–87. https://doi.org/10.1002/alz.13807. source
    • cites [41] Saczynski JS, Rosen AB, McCammon RJ, et al. Antidepressant use and cognitive decline: the health and retirement study. Am J Med. 2015;128:739–46. https://doi.org/10.1016/j.amjmed.2015.01.007. source

      The Discussion and Conclusions report no significant association between antidepressant use and six-year change in cognitive function. The study did not establish a null association with dementia risk, which is a different outcome. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation
    § 4 Discussion · p. 7

    Wang 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.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [40] Wang Y-C, Tai P-A, Poly TN, et al. Increased risk of dementia in patients with antidepressants: a meta-analysis of observational studies. Behav Neurol. 2018;2018:5315098. https://doi.org/10.1155/2018/5315098. source

      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 measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation
    § 4 Discussion · p. 7

    Peakman et al. observed an increased dementia risk after 2.5 years of antidepressant use in older individuals with depression.

    “Peakman et al. [39] observed an increased dementia risk after 2.5 years of antidepressant use in older individuals with depression.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [39] Peakman G, Karunatilake N, Seynaeve M, et al. Clinical factors associated with progression to dementia in people with late-life depression: a cohort study of patients in secondary care. BMJ Open. 2020;10:e035147. https://doi.org/10.1136/bmjopen-2019-035147. source

      The Results report a higher dementia hazard among patients prescribed any antidepressant after depression diagnosis, but the Discussion says this association was not significant after correction for multiple comparisons. The paper reports a mean follow-up of 2.7 years, not an increased risk specifically after 2.5 years of antidepressant use; it also says the analysis could not establish whether antidepressants influenced dementia risk. The cited passages have section labels but no page numbers. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation
    § Key Points · p. 2

    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].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [12] Wang GH-M, Chen W-H, Chang S-H, et al. Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study. BMC Geriatr. 2023;23:825. https://doi.org/10.1186/s12877-023-04475-z. source
    • cites [30] Bali V, Holmes HM, Johnson ML, et al. Comparative effectiveness of second-generation antidepressants in reducing the risk of dementia in elderly nursing home residents with depression. Pharmacotherapy. 2016;36:38–48. https://doi.org/10.1002/phar.1680. source

  • Probably not a substantial claim.

    Study design and conductcitation
    § 4 Discussion · p. 8

    Short- and long-term antidepressant use were defined according to guidelines of depression to estimate duration of drug exposure.

    “We defined short- and long-term antidepressant use according to guidelines of depression (see 3) to estimate duration of drug exposure.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [3] Amrein MA, Hengartner MP, Näpflin M, et al. Prevalence, trends, and individual patterns of long-term antidepressant medication use in the adult Swiss general population. Eur J Clin Pharmacol. 2023;79:1505–13. https://doi.org/10.1007/s00228-023-03559-4. source

      The Methods > Variables section defines short-, medium-, and long-term antidepressant use by quarters with a prescription, and the Introduction discusses recommended treatment durations for depression (page numbers unavailable). The paper does not state that its category boundaries were derived from depression guidelines; it measures prescription duration rather than actual drug exposure. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation
    § Key Points · p. 2

    Cumulative exposure to anticholinergic antidepressants is significantly associated with a higher dementia risk, with effects persisting up to 20 years post-exposure.

    “Studies have demonstrated that cumulative exposure to anticholinergic antidepressants is significantly associated with a higher dementia risk, with effects persisting up to 20 years post-exposure [32].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [32] Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. https://doi.org/10.1136/bmj.k1315. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation
    § 4 Discussion · p. 8

    Previous longitudinal cohort studies indicate that anticholinergic medications negatively affect cognitive performance.

    “This association between anticholinergic antidepressants and dementia aligns with previous longitudinal cohort studies indicating that anticholinergic medications negatively affect cognitive performance [15, 31, 32, 43, 44].”
    Quote in the paperNot a substantial claim5 of 5 sources checked
    • cites [15] Coupland CAC, Hill T, Dening T, et al. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;179:1084–93. https://doi.org/10.1001/jamainternmed.2019.0677. source

      The Introduction says anticholinergic medications can cause confusion and memory loss, and it reports that a prior cohort study associated greater use with increased dementia risk. The References also list longitudinal studies of cognitive impairment and decline. But this paper does not report that those cohorts found poorer cognitive performance specifically, and its own outcome was dementia rather than cognitive performance. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [31] Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175:401–7. https://doi.org/10.1001/jamainternmed.2014.7663. source
    • cites [32] Richardson K, Fox C, Maidment I, et al. Anticholinergic drugs and risk of dementia: case-control study. BMJ. 2018;361:k1315. https://doi.org/10.1136/bmj.k1315. source
    • cites [43] Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332:455–9. https://doi.org/10.1136/bmj.38740.439664.DE. source
    • cites [44] Pieper NT, Grossi CM, Chan W-Y, et al. Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis. Age Ageing. 2020;49:939–47. https://doi.org/10.1093/ageing/afaa090. source

      The Results (Anticholinergics and cognitive decline) report consistently greater cognitive decline among anticholinergic users across pooled studies. But the Introduction describes these as observational associations subject to confounding, so the claim’s wording that the medications negatively affect performance implies a causal conclusion the paper does not establish. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation
    § Key Points · p. 2

    The evidence on the association between antidepressant use and dementia risk is inconsistent and remains uncertain.

    “Previous studies have yielded inconsistent findings; while some suggest a protective effect [18, 19], others report a worsening effect [20-22], and others find no significant association [23, 24].”
    • Also stated in: § Key Points · p. 2 · plain
      “Yet, the influence of antidepressants on dementia risk remains widely uncertain [17].”
    Quote in the paperSubstantial claim4 of 6 sources checked
    • cites [17] Rajkumar RP. Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration. Explor Neuroprot Ther. 2024. https://doi.org/10.37349/ent.2024.00068. source
    • cites [18] Cortes-Flores H, Torrandell-Haro G, Brinton RD. Association between CNS-active drugs and risk of Alzheimer’s and age-related neurodegenerative diseases. Front Psychiatry. 2024;15:1358568. https://doi.org/10.3389/fpsyt.2024.1358568. source
    • cites [19] Jacob L, Bohlken J, Kostev K. Risk of dementia in German patients treated with antidepressants in general or psychiatric practices. Int J Clin Pharmacol Ther. 2017;55:322–8. https://doi.org/10.5414/CP202754. source
    • cites [20] Wang S-M, Han C, Bahk W-M, et al. Addressing the side effects of contemporary antidepressant drugs: a comprehensive review. Chonnam Med J. 2018;54:101. https://doi.org/10.4068/cmj.2018.54.2.101. source

      The review’s Adverse Reactions sections discuss mixed evidence for cardiovascular events and contradictory findings on seizures, but those are different outcomes. Searches for dementia, Alzheimer’s disease, cognitive decline, and protective or worsening effects found no passage addressing whether antidepressant use is associated with dementia risk. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [21] Kodesh A, Sandin S, Reichenberg A, et al. Exposure to antidepressant medication and the risk of incident dementia. Am J Geriatr Psychiatry. 2019;27:1177–88. https://doi.org/10.1016/j.jagp.2019.05.019. source
    • cites [22] Bansal N, Hudda M, Payne RA, et al. Antidepressant use and risk of adverse outcomes: population-based cohort study. BJPsych Open. 2022;8:e164. https://doi.org/10.1192/bjo.2022.563. source

      The Discussion’s summary of findings (page not supplied) lists diabetes, hypertension, cardiovascular outcomes and mortality, but not dementia. Searches for dementia risk, cognitive decline and Alzheimer’s disease found no passage assessing the association between antidepressant use and dementia or describing inconsistent dementia findings. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation
    § 4 Discussion · p. 7

    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.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [37] Wang Y-C, Tai P-A, Poly TN, et al. Increased risk of dementia in patients with antidepressants: a meta-analysis of observational studies. Behav Neurol. 2018;2018:1–8. https://doi.org/10.1155/2018/5315098. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [38] Moraros J, Nwankwo C, Patten SB, et al. The association of antidepressant drug usage with cognitive impairment or dementia, including Alzheimer disease: a systematic review and meta-analysis. Depress Anxiety. 2017;34:217–26. https://doi.org/10.1002/da.22584. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Interpretationcitation
    § 4 Discussion · p. 7

    The study's findings are consistent with prior studies.

    “Our findings are consistent with prior studies [12, 20-22, 27, 36].”
    Quote in the paperNot a substantial claim4 of 6 sources checked
    • cites [12] Wang GH-M, Chen W-H, Chang S-H, et al. Association between first-line antidepressant use and risk of dementia in older adults: a retrospective cohort study. BMC Geriatr. 2023;23:825. https://doi.org/10.1186/s12877-023-04475-z. source
    • cites [20] Wang S-M, Han C, Bahk W-M, et al. Addressing the side effects of contemporary antidepressant drugs: a comprehensive review. Chonnam Med J. 2018;54:101. https://doi.org/10.4068/cmj.2018.54.2.101. source

      The Data Search and Discussion sections review prior research on antidepressant side effects, but the citing sentence does not identify which of its findings are said to agree with that research. Searches for the claimed consistency and for comparisons of antidepressant adverse effects found no passage that establishes whether the unspecified findings agree with this review. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [21] Kodesh A, Sandin S, Reichenberg A, et al. Exposure to antidepressant medication and the risk of incident dementia. Am J Geriatr Psychiatry. 2019;27:1177–88. https://doi.org/10.1016/j.jagp.2019.05.019. source
    • cites [22] Bansal N, Hudda M, Payne RA, et al. Antidepressant use and risk of adverse outcomes: population-based cohort study. BJPsych Open. 2022;8:e164. https://doi.org/10.1192/bjo.2022.563. source
    • cites [27] Chan JYC, Yiu KKL, Kwok TCY, et al. Depression and antidepressants as potential risk factors in dementia: a systematic review and meta-analysis of 18 longitudinal studies. J Am Med Dir Assoc. 2019;20:279-286.e1. https://doi.org/10.1016/j.jamda.2018.12.004. source
    • cites [36] Leng Y, Diem SJ, Stone KL, et al. Antidepressant use and cognitive outcomes in very old women. J Gerontol A Biol Sci Med Sci. 2018;73:1390–5. https://doi.org/10.1093/gerona/glx226. source

  • It may state two separate claims as one.

    Findingown data
    § 3.3 Long-Term Tricyclic Antidepressants Users · p. 4

    Altogether 3579 (18.7%) of long-term antidepressant users had at least one prescription of TCA, and 1564 (8.2%) had only TCAs prescriptions during the whole study period.

    “Altogether 3579 (18.7%) of long-term antidepressant users had at least one prescription of TCA (see Online Resource 8) and 1564 (8.2%) of long-term antidepressant users had only TCAs prescriptions during the whole study period (monotherapy).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data
    § 4 Discussion · p. 7

    Long-term antidepressant use of more than 2 years is associated with increased odds of all-cause dementia compared with no use in adults aged 65 years and older, OR 1.92 (95% CI 1.72-2.15, p < 0.001), after adjustment for a wide range of comorbidities.

    “we found that longterm antidepressant use of more than 2 years was associated with an increased risk of all-cause dementia after adjustment for a wide range of comorbidities”
    • Also stated in: § 4 Discussion · p. 7 · boosted
      “demonstrating a 1.92-fold increased odd developing dementia among long-term antidepressant users compared with nonusers in a large Swiss cohort”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data
    § Abstract · p. 1

    Long-term antidepressant use was significantly associated with higher odds of dementia compared with propensity score matched nonusers (OR 1.92, 95% CI 1.72-2.15, p < 0.001), after adjusting for significant covariates.

    “After adjusting for covariates, long-term antidepressant use was significantly associated with dementia (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.72-2.15, p < 0.001).”
    • Also stated in: § Key Points · p. 1 · plain
      “Long-term antidepressant use was associated with higher odds of developing dementia compared with propensity score matched non-users, after adjusting for multiple covariates.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: PCGs adequately capture morbidity in claims data where diagnostic information is limited.
    • Rests on an assumption: The ICD-10 codes and antidementia drug prescriptions used to define dementia accurately identify incident dementia.
    • Rests on an assumption: There are no unmeasured confounders that bias the association between long-term antidepressant use and dementia.
    • Rests on an assumption: The propensity score model is correctly specified.
    • Rests on an assumption: The 2-3 year treatment phase and 1-year outcome phase are sufficient to detect incident dementia.
    • Rests on an assumption: Depression diagnosis from inpatient stays adequately captures depression as a confounder.

  • It may state two separate claims as one.

    Findingown data
    § 4 Discussion · p. 8

    Among long-term antidepressant users aged 65 years and older, 1564 (8.2%) were prescribed only TCAs for more than 2 years, and 3579 (18.7%) had at least one TCA prescription in addition to other antidepressants.

    “Descriptive analysis revealed that 1564 (8.2%) of longterm antidepressant users aged 65 years and older were prescribed only TCAs for more than 2 years, and 3579 (18.7%) had at least one TCA prescription in addition to other antidepressants.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data
    § 3.3 Long-Term Tricyclic Antidepressants Users · p. 6

    In the long-term tricyclic antidepressant use group 4.2% developed dementia, compared with 2.5% in the no-use control group.

    “In the long-term tricyclic antidepressant use group 4.2% developed dementia and in the no-use control group 2.5% developed dementia”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Findingown data
    § 3.3 Long-Term Tricyclic Antidepressants Users · p. 4

    There was a small sex difference in TCA monotherapy, with 8.6% of women and 7.1% of men receiving long-term tricyclic antidepressants only.

    “There was a small sex difference in monotherapy, as 8.6% of women and 7.1% of men received longterm tricyclic antidepressants only.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data
    § Abstract · p. 1

    Long-term antidepressant and long-term TCAs use is associated with an increased risk of dementia in older adults, even after accounting for various comorbidities.

    “These findings suggest that long-term antidepressant and long-term TCAs use is associated with an increased risk of dementia in older adults, even after accounting for various comorbidities.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: PCGs adequately capture morbidity in claims data where diagnostic information is limited.
    • Rests on an assumption: The ICD-10 codes and antidementia drug prescriptions used to define dementia accurately identify incident dementia.
    • Rests on an assumption: There are no unmeasured confounders that bias the association between long-term antidepressant use and dementia.
    • Rests on an assumption: The propensity score model is correctly specified.
    • Rests on an assumption: The 2-3 year treatment phase and 1-year outcome phase are sufficient to detect incident dementia.
    • Rests on an assumption: Depression diagnosis from inpatient stays adequately captures depression as a confounder.

  • Probably not a substantial claim.

    Interpretationnone given
    § Key Points · p. 2

    The healthcare claims data used in this study come from a large, representative sample of the older Swiss population.

    “We conduct a longitudinal, propensity score matched analysis of healthcare claims data from a large, representative sample.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Helsana insurees are representative of the older Swiss population.

  • It may state two separate claims as one.

    Study design and conductreasoning
    § 4 Discussion · p. 8

    Dementia ascertainment may have been incomplete, as outpatient diagnoses were unavailable and inpatient diagnoses likely reflect later disease stages.

    “dementia ascertainment may have been incomplete.”
    • Also stated in: § 4 Discussion · p. 8 · hedged
      “outpatient diagnoses were unavailable, and inpatient diagnoses likely reflect later disease stages.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation
    § 4 Discussion · p. 8

    TCAs are generally not recommended as first-line treatments in older adults owing to their anticholinergic effects and the potential for adverse reactions such as falls and fractures.

    “TCAs are generally not recommended as first-line treatments in this age group owing to their anticholinergic effects and the potential for adverse reactions such as falls and fractures [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Hatzinger M, Hemmeter U, Hirsbrunner T, et al. Empfehlungen für Diagnostik und Therapie der Depression im Alter (Not Available). Praxis (Bern 1994). 2018;107:127–44. https://doi.org/10.1024/1661-8157/a002883. source

  • It may state two separate claims as one.

    Interpretationreasoning
    § 4 Discussion · p. 7

    Because individuals with antidepressant use within 1 year prior to the observation period were excluded and the inpatient diagnosis of depression was equally balanced between groups, the findings should be less affected by protopathic bias and indication bias owing to depression.

    “As we excluded individuals with antidepressant use within 1 year prior to the observation period, and the inpatient diagnosis of depression was equally balanced between groups, our findings should be less affected by both protopathic bias and indication bias owing to depression.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. It may state two separate claims as one.

    Study design and conductnone given
    § 2.5 Statistics · p. 3

    The adjustment was performed to account for potential residual imbalance after matching and to obtain more robust and consistent estimators.

    “The adjustment was performed to account for potential residual imbalance after matching and to obtain more robust and consistent estimators.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Interpretationcitation
    § 4 Discussion · p. 8

    Indirect factors such as polypharmacy and its associated risks may also play a role in the association, given the high prevalence of comorbidities and concurrent medication use in the elderly population.

    “Indirect factors, such as polypharmacy and its associated risks, may also play a role, given the high prevalence of comorbidities and concurrent medication use in the elderly population [16].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Davies EA, O’Mahony MS. Adverse drug reactions in special populations - the elderly. Br J Clin Pharmacol. 2015;80:796–807. https://doi.org/10.1111/bcp.12596. source

  • It may state two separate claims as one.

    Study design and conductnone given
    § 4 Discussion · p. 8

    Lifestyle factors (e.g., smoking, physical activity), genetic predisposition, and psychosocial variables were not accounted for, which could influence dementia risk.

    “lifestyle factors (e.g., smoking, physical activity), genetic predisposition, and psychosocial variables were not accounted for, which could influence dementia risk.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. It may state two separate claims as one.

    Study design and conductnone given
    § 4 Discussion · p. 8

    Prodromal neuropsychiatric symptoms may occur several years before formal dementia diagnosis, and antidepressant initiation may therefore partly reflect underlying disease in its early stages.

    “Prodromal neuropsychiatric symptoms may occur several years before formal diagnosis, and antidepressant initiation may therefore partly reflect underlying disease in its early stages.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductown data
    § 3 Results · p. 4

    After exclusions for dementia during the treatment phase, the final sample comprised 19,155 long-term antidepressant users and 20,648 matched nonusers.

    “Totally 2845 individuals were excluded owing to dementia during the treatment phase, yielding a final sample of 19,155. A matched control group included 22,000 weighted cases with no antidepressant prescriptions, with 1352 exclusions for dementia during the treatment phase, yielding 20,648 in the no-use control group.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductreasoning
    § 4 Discussion · p. 8

    The observational nature of the study precludes causal inference, and residual confounding may persist despite matching.

    “the observational nature of the study precludes causal inference, and residual confounding may persist despite matching.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Study design and conductreasoning
    § 2.5 Statistics · p. 3

    Robust standard errors were used for all post-matching regression analyses to account for the matched study design.

    “To account for the matched study design, robust standard errors were used for all post matching regression analyses.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductnone given
    § 2.5 Statistics · p. 3

    A landmark design was used, in which individuals were classified at a fixed time point and required to be alive and without a dementia diagnosis at that time, with follow-up for outcomes beginning thereafter.

    “A landmark design was used, in which individuals were classified at a fixed time point and required to be alive and without a dementia diagnosis at that time, with follow-up for outcomes beginning thereafter.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductnone given
    § 2.3 Outcome · p. 3

    The dataset includes only ICD-10 diagnosis from inpatient stays.

    “The dataset includes only ICD-10 diagnosis from inpatient stays.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductreasoning
    § 4 Discussion · p. 8

    Depression was identified using inpatient diagnoses only, likely capturing more severe cases while missing individuals treated exclusively in outpatient settings.

    “Depression was identified using inpatient diagnoses only, likely capturing more severe cases while missing individuals treated exclusively in outpatient settings.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductown data
    § 3.3 Long-Term Tricyclic Antidepressants Users · p. 6

    Baseline characteristics were well-balanced between the long-term tricyclic antidepressant use group and the no-use control group, for example antipsychotic use (9.4% vs 9.3%) and living in a nursing home (6.6% vs 6.5%).

    “They were well-balanced across, for example, taking antipsychotics (long-term group = 9.4% and control group = 9.3%) or whether individuals are living in a nursing home (long-term group = 6.6% and control group = 6.5%).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationreasoning
    § 5 Conclusions · p. 9

    The finding of increased dementia risk applies to both TCA use and other antidepressant drug classes, indicating that anticholinergic effects are not the sole putative causal mechanism.

    “This finding applies to both use of TCAs and other antidepressant drug classes, indicating that anticholinergic effects are not the sole putative causal mechanism.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductnone given
    § 4 Discussion · p. 8

    The application of propensity score matching enhanced the methodological strength of the study by reducing confounding effects.

    “The application of propensity score matching enhanced the methodological strength by reducing confounding effects.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductreasoning
    § 2.4 Covariates · p. 3

    Because diagnostic information is not comprehensively available in claims data, PCGs were used as a proxy to capture morbidity on the basis of prescribed medications.

    “Because diagnostic information is not comprehensively available in claims data, PCGs were used as a proxy to capture morbidity on the basis of prescribed medications.”
    Quote in the paperSubstantial claim
35 of 35

  • The paper relies on this without support.

    PCGs adequately capture morbidity in claims data where diagnostic information is limited.

    “PCGs represent a well-established pharmaceutical classification system commonly applied in settings with limited clinical diagnostic data.”

  • The paper relies on this without support.

    The ICD-10 codes and antidementia drug prescriptions used to define dementia accurately identify incident dementia.

    “We assessed dementia incidence using ICD-10 codes F00, F01, F02, F03, G30, G31.0, G31.1, or G31.82, and the prescription of antidementia medications (ATC code N06D) within the outcome phase.”

  • The paper relies on this without support.

    There are no unmeasured confounders that bias the association between long-term antidepressant use and dementia.

    “To balance differences in baseline characteristics between long-term antidepressant users and nonusers, we applied variable ratio propensity score matching using a nearest neighbor algorithm, allowing up to 12 control individuals per treated individual (mean matching ratio ≈ 3).”

  • The paper relies on this without support.

    The propensity score model is correctly specified.

    “In addition, a propensity score was estimated using logistic regression on the basis of further covariates described in the methods section and was used as the distance measure for nearest neighbor matching.”

  • The paper relies on this without support.

    Helsana insurees are representative of the older Swiss population.

    “Basic insurance is mandatory in Switzerland, and in 2023, the Helsana Group covered 14.5% (1,296,439) of the Swiss population.”

  • The paper relies on this without support.

    The 2-3 year treatment phase and 1-year outcome phase are sufficient to detect incident dementia.

    “The treatment phase extended from the index date for 2-3 years (11 quarters) and was followed by a one-year outcome phase.”

  • The paper relies on this without support.

    Depression diagnosis from inpatient stays adequately captures depression as a confounder.

    “Exact matching was performed on a predefined set of key covariates, including index month and year, age, sex, nursing home residence, depression diagnosis, and the use of antipsychotics, anxiolytics, hypnotics, or sedatives.”

  • The paper relies on this without support.

    The Helsana dataset used is nearly representative of the older Swiss adult population.

    “A major strength of this study is the use of a large, nearly representative dataset with detailed prescription and diagnostic records, enabling robust longitudinal analyses.”
8 of 8

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Regression table covariate counts exceed the stated sample

    Major

    The antipsychotic rows contain 67,866 people and 2,578 dementia cases, although the table states N = 39,803. The table's two study-group rows report only 1,463 dementia cases, so these covariate counts cannot describe the stated analysis sample.

  • TCA recipients are alternately counted as including and excluding monotherapy

    Minor

    The results say the 3,579 people with at least one TCA prescription include 1,564 who received only TCAs. The discussion instead describes all 3,579 as receiving TCAs in addition to other antidepressants.

2 of 2

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1016/s0140-6736(20)30367-6

    Major

    The cited work was retracted on 2023-05-01 (notice 10.1016/s2468-2667(23)00083-x), before this paper was published (2026-06-10). Its authors could have known.

    Cited work 10.1016/s0140-6736(20)30367-6 · retracted 2023-05-01 · notice 10.1016/s2468-2667(23)00083-x · this paper published 2026-06-10

1 of 1

Citations

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. Wang Y-C, Tai P-A, Poly TN, et al. Increased risk of dementia in patients with antidepressants: a meta-analysis of observational studies. Behav Neurol. 2018;2018:5315098. https://doi.org/10.1155/2018/5315098. · DOI · Paper page

Cited by

Still being checked.

Related

Metadata

Authors
Amrein, M. A., Hengartner, M. P., Näpflin, M., Farcher, R., & Huber, C. A.
Affiliations
  • Helsana Group (Switzerland) (CH)
  • Kalaidos University of Applied Sciences (CH)
  • University of Zurich (CH)
Corresponding author
Farcher, Renato
ORCID
Venue
Drugs - Real World Outcomes
Publisher
Springer Science and Business Media LLC
Published
2026-06-10
Volume
13
Issue
3
Pages
329-338
ISSN
  • 2198-9788 (ISSN-L)
  • 2199-1154
DOI
10.1007/s40801-026-00560-y
PMC
PMC13570850
OpenAlex
W7164170819
Semantic Scholar
0cd3cc91f4482af5d9c8842db9afe6dea534f829
Cited by
0
References
40
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Drugs - Real World Outcomes (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords
antidepressants, dementia risk, long-term antidepressant use, tricyclic antidepressants, older adults, incident dementia, drug safety, comorbidities

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