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Cited by 45Dementia and Cognitive Impairment ResearchPharmaceutical Practices and Patient OutcomesTreatment of Major Depression

The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index; 25 of the 46 sources its claims cite were checked for support.

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

Open access
Mo, Minjia, Abzhandadze, Tamar, Hoang, Minh Tuan, Sacuiu, Simona, Jurado, Pol Grau, Pereira, Joana B., Naia, Luana, Kele, Julianna, Maioli, Silvia, Xu, Hong, Eriksdotter, Maria, Garcia-Ptacek, Sara·2025·BMC Medicine
DOI 10.1186/s12916-025-03851-3PMC PMC11854023
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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.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

In a Swedish national dementia cohort, current antidepressant use was associated with faster MMSE decline, especially SSRIs and mirtazapine, and higher SSRI doses were linked to greater cognitive decline and higher risks of severe dementia, fracture, and death. The authors caution that the observational findings cannot distinguish drug effects from the underlying psychiatric indication.

Key findings

  • Among 18,740 patients with dementia (10,205 women [54.5%]; mean age 78.2 years), 4,271 (22.8%) received at least one antidepressant prescription; SSRIs accounted for 64.8% of 11,912 prescriptions.
  • Antidepressant use was associated with faster cognitive decline (β = −0.30 points/year; 95% CI, −0.39 to −0.21), with significant associations for SSRIs (β = −0.39; 95% CI, −0.50 to −0.28) and other antidepressants (β = −0.20; 95% CI, −0.35 to −0.05), and for sertraline, citalopram, escitalopram, and mirtazapine.
  • Compared with sertraline, escitalopram showed faster decline (β = −0.51 points/year; 95% CI, −0.89 to −0.12), while citalopram showed slower decline (β = 0.28; 95% CI, 0.17 to 0.39).
  • Higher SSRI doses (>1.0 DDD) were associated with increased risk of severe dementia (HR = 1.35; 95% CI, 1.02 to 1.80), all-cause mortality (HR = 1.18; 95% CI, 1.07 to 1.31), and fracture (HR = 1.25; 95% CI, 1.10 to 1.43).

Methods

  • Population-based national cohort using Swedish registers (SveDem, National Patient Register, Prescribed Drug Register, Cause of Death Registry), including patients with incident dementia from May 1, 2007, to October 16, 2018, with at least one follow-up and new antidepressant use.
  • Antidepressant exposure was time-varying, defined by dispensations in the 6 months before dementia diagnosis or each follow-up; doses were expressed as defined daily doses (DDD).
  • Linear mixed models estimated MMSE change over time; Cox proportional hazards models estimated severe dementia (MMSE < 10), fracture, and death, with competing-risk models for severe dementia and fracture, plus sensitivity and subgroup analyses.

Limitations

  • The authors state the main concern is indication bias: depression itself is linked to cognitive impairment, so associations may reflect the indication rather than the drug; they repeated analyses among patients without depression and found consistent results.
  • They note that depression diagnoses came from specialized care and likely missed milder primary-care depression, lacked depression severity and actual intake data, and could be affected by channeling bias in drug comparisons.
  • They also state that dementia severity may independently contribute to cognitive decline, SveDem has patient loss to follow-up and incomplete national coverage (100% of memory clinics, 75% of primary care units, about one-third of expected new dementia cases), and some analyses were imprecisely estimated due to small subgroups. Evident from the text: the observational design cannot establish causality.

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

Integrity signals

Registry

Crossref · 10.1186/s12916-025-03851-3

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

25 of 46 cited sources checked · 16 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    In the majority of cases reported, antidepressants had the same effect on cognition as placebo.

    “In the majority of the cases reported, antidepressants had the same effect on cognition as placebo [44–47]”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [44] Dudas R, Malouf R, McCleery J, Dening T. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2018;8(8):CD003944. source
    • cites [45] Maier F, Spottke A, Bach JP, Bartels C, Buerger K, Dodel R, et al. Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(5): e206027. source
    • cites [46] Mowla A, Mosavinasab M, Haghshenas H, Borhani HA. Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer’s dementia? A double-blind, placebo-controlled clinical trial. J Clin Psychopharmacol. 2007;27(5):484–7. source
    • cites [47] Qin M, Wu J, Zhou Q, Liang Z, Su Y. Global cognitive effects of second-generation antidepressants in patients with Alzheimer’s disease: A systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res. 2022;155:371–9. source
  • Interpretationcitation

    The magnitude of the effect of citalopram (0.41 points/year), sertraline (0.25 points/year), and escitalopram (0.76 points/year) appears to be lower than the minimum clinically significant change in MMSE score of 1-3 points.

    “However, the magnitude of the effect of citalopram (0.41 points/year), sertraline (0.25 points/year), and escitalopram (0.76 points/year) appears to be lower than the minimum clinically significant change in MMSE score of 1–3 points [53].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [53] Andrews JS, Desai U, Kirson NY, Zichlin ML, Ball DE, Matthews BR. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer’s disease clinical trials. Alzheimers Dement (N Y). 2019;5:354–63. source
  • Premisecitation

    The Swedish Prescribed Drug Register provides complete data on dispensation of prescription medications from all pharmacies since July 2005.

    “The Swedish Prescribed Drug Register provides complete data on dispensation of prescription medications from all pharmacies since July 2005 [27].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Wettermark B, Hammar N, Fored CM, Leimanis A, Otterblad Olausson P, Bergman U, et al. The new Swedish Prescribed Drug Register–opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf. 2007;16(7):726–35. source
  • Premisecitation

    Depression has been linked with dementia and cognitive impairment in normal people with depression.

    “Depression has been linked with dementia and cognitive impairment in normal people with depression [41, 42]”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [41] Byers AL, Yaffe K. Depression and risk of developing dementia. Nat Rev Neurol. 2011;7(6):323–31. source
    • cites [42] Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF 3rd. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202(5):329–35. source

      The Abstract reports cognitive impairment in older adults with late-life depression, and the Results report a significant association between late-life depression and dementia risk. The claim's reference to “normal people with depression” is broader than the older-adult population addressed by this paper. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Findingown data

    Use of anxiolytics modified the association between antidepressant use and cognitive decline (P for interaction < 0.05).

    “Modifying effects of sex and use of anxiolytics on the association between antidepressant use and cognitive decline were observed (P for interaction < 0.05).”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: A linear trend over time was assumed in the mixed model.
  • Probably not a substantial claim. 27
  • It may state two separate claims as one. 22
  • The quote only partly states this claim. 3

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

    Premisecitation

    Previous studies of antidepressant use and cognitive decline in people with dementia have shown mixed findings.

    “Previous studies of antidepressant use and cognitive decline in people with dementia have shown mixed findings.”
    Quote in the paperNot a substantial claim3 of 6 sources checked
    • cites [43] Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682–91. source
    • cites [44] Dudas R, Malouf R, McCleery J, Dening T. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2018;8(8):CD003944. source

      The Cognitive function results report probably little or no difference in MMSE scores between antidepressant and placebo groups across five studies, with no observed heterogeneity (I² = 0%). The Discussion’s Summary of main results likewise reports little or no difference in cognitive function, rather than mixed findings. The review concerns patients with both depression and dementia; it does not establish a broader claim about all people with dementia. (LLM, conf=0.78)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [45] Maier F, Spottke A, Bach JP, Bartels C, Buerger K, Dodel R, et al. Bupropion for the Treatment of Apathy in Alzheimer Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(5): e206027. source

      The Results report no statistically significant difference between bupropion and placebo on two cognitive measures, but do not characterize findings across previous studies. The Discussion addresses prior studies of apathy, not mixed findings on antidepressant use and cognitive decline in people with dementia. Searches for antidepressants, cognition, and cognitive decline found no passage addressing that claim; page numbers were not provided in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites [46] Mowla A, Mosavinasab M, Haghshenas H, Borhani HA. Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer’s dementia? A double-blind, placebo-controlled clinical trial. J Clin Psychopharmacol. 2007;27(5):484–7. source
    • cites [47] Qin M, Wu J, Zhou Q, Liang Z, Su Y. Global cognitive effects of second-generation antidepressants in patients with Alzheimer’s disease: A systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res. 2022;155:371–9. source
    • cites [48] Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology. 2000;55(9):1271–8. source

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

    Premisecitation

    Some clinical trials reported a significant decline on the MMSE scores in antidepressant users.

    “but some reported a significant decline on the MMSE scores in antidepressant users [43, 48].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [43] Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682–91. source
    • cites [48] Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology. 2000;55(9):1271–8. source

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

    Premisecitation

    Other RCTs in AD indicated that sertraline and escitalopram had no effect on cognitive function.

    “In contrast, other RCTs in AD indicated that another two SSRIs, sertraline and escitalopram, had no effect on cognitive function [49, 50].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [49] Choe YM, Kim KW, Jhoo JH, Ryu SH, Seo EH, Sohn BK, et al. Multicenter, randomized, placebo-controlled, double-blind clinical trial of escitalopram on the progression-delaying effects in Alzheimer’s disease. Int J Geriatr Psychiatry. 2016;31(7):731–9. source
    • cites [50] Munro CA, Longmire CF, Drye LT, Martin BK, Frangakis CE, Meinert CL, et al. Cognitive outcomes after sertaline treatment in patients with depression of Alzheimer disease. Am J Geriatr Psychiatry. 2012;20(12):1036–44. source

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

    Premisecitation

    A recently conducted RCT reported worsening of cognition in patients with AD who used citalopram over 9 weeks.

    “A recently conducted RCT reported worsening of cognition in patients with AD who used citalopram over 9 weeks [43].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [43] Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682–91. source

  • Probably not a substantial claim.

    Premisecitation

    When multiple dispensations were used, their defined daily doses were added.

    “When multiple dispensations were used, their DDD were added [36].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [36] Xu H, Garcia-Ptacek S, Jonsson L, Wimo A, Nordstrom P, Eriksdotter M. Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality. Neurology. 2021;96(17):e2220–30. source

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

    Premisecitation

    The National Patient Register contains nationwide records on inpatient care since 1987 and more than 80% of specialized outpatient care since 2001.

    “The National Patient Register contains nationwide records on inpatient care since 1987 and more than 80% of specialized (hospital-based) outpatient care since 2001 [26].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [26] Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450. source

      The Background states that the Inpatient Register, part of the National Patient Register, has had complete national coverage since 1987. In “History and coverage of the IPR,” the paper says counties have been obliged to report hospital-based outpatient physician visits since 2001, but gives outpatient coverage as about 80%, not more than 80%; it does not establish that this level of coverage held throughout the period since 2001. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim.

    Study design and conductcitation

    The analysis included inverse probability of censoring weighting to account for dropout or competing risk before the end of follow-up such as death.

    “We also included the inverse probability of censoring weighting considering the potential effects of dropout or to the presence of a competing risk before the end of follow-up such as death [40].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [40] Handels R, Jonsson L, Garcia-Ptacek S, Eriksdotter M, Wimo A. Controlling for selective dropout in longitudinal dementia data: Application to the SveDem registry. Alzheimers Dement. 2020;16(5):789–96. source

      The Methods (Statistical analysis; page unavailable) describe using inverse probability of censoring weights to account for dropout. But they define dropout to exclude cases where death occurred within the subsequent year, so the paper does not support the claim that its weighting also accounted for death as a competing risk. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Laura et al. found that citalopram can partially restore the dysfunctional prefrontal cortical systems by increasing serotonergic neurotransmission in FTD.

    “In line with our observation, Laura et al. [56] found that citalopram can partially restore the dysfunctional prefrontal cortical systems by increasing serotonergic neurotransmission in FTD.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [56] Hughes LE, Rittman T, Regenthal R, Robbins TW, Rowe JB. Improving response inhibition systems in frontotemporal dementia with citalopram. Brain. 2015;138(Pt 7):1961–75. source

  • It may state two separate claims as one.

    Premisecitation

    Antidepressants do not seem to work as well in patients with dementia, possibly because depression in dementia is a different illness than depression in people with intact cognition.

    “However, antidepressants do not seem to work as well in patients with dementia, possibly because “depression in dementia is a different illness” than depression in people with intact cognition [54].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [54] Alexopoulos GS, Manning K, Kanellopoulos D, McGovern A, Seirup JK, Banerjee S, Gunning F. Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant. Psychol Med. 2015;45(14):3111–20. source

      The Discussion reports poorer escitalopram outcomes in older adults with impaired cognitive control. But the Methods > Subjects section does not identify a dementia group, and the paper does not compare antidepressant response in patients with and without dementia or suggest that depression in dementia is a different illness. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim.

    Study design and conductcitation

    A sensitivity analysis among patients without depression was performed to reduce indication bias.

    “Since depression itself has been linked with dementia and cognitive impairment [41, 42], we did a sensitivity analysis among patients without depression to reduce the indication bias.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [41] Byers AL, Yaffe K. Depression and risk of developing dementia. Nat Rev Neurol. 2011;7(6):323–31. source
    • cites [42] Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF 3rd. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202(5):329–35. source

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

    Premisecitation

    DLB and PDD share pathological and clinical characteristics, are considered part of a continuum within the spectrum of LBD, and were therefore merged for this study as LBDs.

    “DLB and PDD share pathological and clinical characteristics, are considered part of a continuum within the spectrum of LBD [33, 34], and were therefore merged for this study as LBDs.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [33] Fereshtehnejad SM, Religa D, Westman E, Aarsland D, Lokk J, Eriksdotter M. Demography, diagnostics, and medication in dementia with Lewy bodies and Parkinson’s disease with dementia: data from the Swedish Dementia Quality Registry (SveDem). Neuropsychiatr Dis Treat. 2013;9:927–35. source

      The Introduction says DLB and PDD overlap clinically, and the Discussion notes that some studies found similar histopathological features. But the Introduction calls it controversial whether they are one entity or two distinct conditions; it does not establish that they form a continuum. The decision to merge them is the citing study’s own method, not a claim attributed to this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [34] Ballard C, Garcia-Ptacek S, van Steenoven I, Aarsland D. 241Spectrum of Lewy body dementias: relationship of Parkinson’s disease dementia to dementia with Lewy bodies. In: Emre M, editor. Cognitive Impairment and Dementia in Parkinson's Disease: Oxford University Press; 2015. p. 0. source

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

    Premisecitation

    In a RCT (n = 95) among older adults with major depression and memory complaints, a combination of memantine and escitalopram significantly improved delayed recall and executive functioning at 12 months.

    “In a RCT (n = 95) among older adults with major depression and memory complains, a combination of memantine and escitalopram significantly improved delayed recall and executive functioning at 12 months [58].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [58] Lavretsky H, Laird KT, Krause-Sorio B, Heimberg BF, Yeargin J, Grzenda A, et al. A Randomized Double-Blind Placebo-Controlled Trial of Combined Escitalopram and Memantine for Older Adults With Major Depression and Subjective Memory Complaints. Am J Geriat Psychiat. 2020;28(2):178–90. source

  • It may state two separate claims as one.

    Study design and conductcitation

    The dementia diagnostic workup follows standard clinical practice, and few patients have a changed dementia diagnosis at follow-up, which suggests adequate diagnostic accuracy.

    “However, the dementia diagnostic workup follows standard clinical practice, and few patients have a changed dementia diagnosis at follow-up, which suggests adequate diagnostic accuracy [65].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [65] Garcia-Ptacek S, Farahmand B, Kareholt I, Religa D, Cuadrado ML, Eriksdotter M. Mortality risk after dementia diagnosis by dementia type and underlying factors: a cohort of 15,209 patients based on the Swedish Dementia Registry. J Alzheimers Dis. 2014;41(2):467–77. source

  • It may state two separate claims as one.

    Study design and conductcitation

    The national coverage of SveDem for new dementia cases is not absolute; it covers 100% of memory clinics and 75% of primary care units, and almost one-third of all expected new dementia cases in Sweden.

    “Furthermore, the national coverage of SveDem for new dementia cases is not absolute, it covers 100% of memory clinics and 75% of primary care units, and almost one-third of all expected new dementia cases in Sweden [63, 64].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [63] SveDem. Svenska Demensregistret Årsrapport 2022 Sweden2022. Available from: https://www.ucr.uu.se/svedem/om-svedem/arsrapporter/svedemarsrapport-2022/viewdocument/1077. Cited 2023 Oct 18.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [64] Mo M, Zacarias-Pons L, Hoang MT, Mostafaei S, Jurado PG, Stark I, et al. Psychiatric Disorders Before and After Dementia Diagnosis. JAMA Netw Open. 2023;6(10): e2338080. source

      The Discussion’s Strengths and Limitations section states that, according to incidence estimates, SveDem captured almost one-third of expected new dementia cases in Sweden, supporting the claim that its case coverage is not absolute. Our copy does not state that SveDem covers 100% of memory clinics or 75% of primary care units; the Methods mention those types of diagnostic unit but give no coverage percentages. No page number is available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    Population-based cohort studies have found that antidepressant use was related to no or lower risks of all-cause mortality in patients with dementia, but increased risk of fracture.

    “Population-based cohort studies have found that antidepressant use was related to no or lower risks of all-cause mortality in patients with dementia [59, 60], but increased risk of fracture [61, 62].”
    Quote in the paperNot a substantial claim2 of 4 sources checked
    • cites [59] Su JA, Chang CC, Wang HM, Chen KJ, Yang YH, Lin CY. Antidepressant treatment and mortality risk in patients with dementia and depression: a nationwide population cohort study in Taiwan. Ther Adv Chronic Dis. 2019;10:2040622319853719.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [60] Enache D, Fereshtehnejad SM, Kareholt I, Cermakova P, Garcia-Ptacek S, Johnell K, et al. Antidepressants and mortality risk in a dementia cohort: data from SveDem, the Swedish Dementia Registry. Acta Psychiatr Scand. 2016;134(5):430–40. source
    • cites [61] Zakarias JK, Norgaard A, Jensen-Dahm C, Gasse C, Laursen TM, Palm H, et al. Risk of hospitalization and hip fracture associated with psychotropic polypharmacy in patients with dementia: A nationwide register-based study. Int J Geriatr Psychiatry. 2021;36(11):1691–8. source

      The Accepted Article discussion reports earlier cohort studies finding increased fracture risk with antidepressant monotherapy in patients with dementia. But this paper’s own Risk of hip fracture results found no association for antidepressants combined with antipsychotics versus antipsychotics alone. The citation therefore supports the fracture-risk statement as a report of earlier findings, not as a finding of this cohort. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [62] Bakken MS, Engeland A, Engesaeter LB, Ranhoff AH, Hunskaar S, Ruths S. Increased risk of hip fracture among older people using antidepressant drugs: data from the Norwegian Prescription Database and the Norwegian Hip Fracture Registry. Age Ageing. 2013;42(4):514–20. source

  • The quote only partly states this claim.

    Findingown data

    Compared with sertraline, citalopram was associated with slower cognitive decline (β = 0.28 points/year; 95% CI 0.17 to 0.39).

    “citalopram (SSRI) (β = 0.28 points/year; 95% CI, 0.17 to 0.39) showed slower cognitive decline”
    • Also stated in: § Antidepressant and cognitive decline by antidepressant class and individual drugs · plain
      “| Citalopram (SSRI) | 0.28 (0.17, 0.39) | < .001 |”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: A linear trend over time was assumed in the mixed model.

  • It may state two separate claims as one.

    Findingown data

    Similar results were observed in sensitivity analyses among patients diagnosed with AD and mixed dementia, patients without depression, or patients with baseline MMSE ≥10 and without depression.

    “Similar results were observed in sensitivity analysis among patients diagnosed with AD and mixed dementia, patients without depression or patients with baseline MMSE ≥ 10 and without depression”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: A linear trend over time was assumed in the mixed model.

  • The quote only partly states this claim.

    Findingown data

    Higher dispensed doses of SSRIs were associated with higher risk of all-cause mortality.

    “dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed”
    • Also stated in: § Conclusions · plain
      “higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The effect size of cognitive decline was greater in men than in women.

    “Compared with patients who were women, had higher MMSE score at baseline, using anxiolytics and hypnotics, the effect size of cognitive decline was greater in those who were men, had lower MMSE score, not using anxiolytics or hypnotics.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: A linear trend over time was assumed in the mixed model.

  • It may state two separate claims as one.

    Findingown data

    There were no significant differences between subgroups of coresident status, type of diagnostic unit, living in nursing home, calendar year of dementia diagnosis, and current use of antipsychotics on cognitive decline.

    “There were no significant differences between subgroups of coresident status, type of diagnostic unit, living in nursing home, calendar year of dementia diagnosis, and current use of antipsychotics on cognitive decline.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: A linear trend over time was assumed in the mixed model.

  • It may state two separate claims as one.

    Findingown data

    Antidepressant use was associated with faster cognitive decline in patients with different MMSE scores at dementia diagnosis, though the effect size of cognitive decline was greater in patients with lower MMSE score.

    “However, we observed antidepressant use was associated with faster cognitive decline in patients with different MMSE scores at dementia diagnosis, though the effect size of cognitive decline was greater in patients with lower MMSE score.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Antidepressant dispensation data accurately reflect actual antidepressant intake.

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

    Study design and conductcitation

    Dementia disorders were clinically diagnosed and recorded according to ICD-10 codes, with McKeith criteria for DLB, Lund-Manchester criteria for FTD, and Movement Disorder Society Task Force criteria for PDD.

    “Dementia disorders are clinically diagnosed and recorded according to the International Classification of Diseases, Tenth Revision (ICD-10) codes [29], with the McKeith criteria [30] used for DLB, the Lund-Manchester criteria [31] for FTD, and the Movement Disorder Society Task Force criteria [32] for PDD, respectively”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [29] Organization WH. The ICD-10 classification of mental and behavioural disorders, clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992.
    • cites [30] Castagnini A, Berrios GE. Acute and transient psychotic disorders (ICD-10 F23): a review from a European perspective. Eur Arch Psychiatry Clin Neurosci. 2009;259(8):433–43. source
    • cites [31] Association AP. Diagnostic and statistical manual of mental disorders (DSM-IV). 4th ed. Washington, DC: American Psychiatric Association; 1994.

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

    Study design and conductnone given

    The Swedish unique personal identity number was used to identify patients across sources and to merge data.

    “The Swedish unique personal identity number was used to identify patients across sources and to merge data.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductnone given

    For patients diagnosed with AD, mixed dementia, and LBD, models were further adjusted for ChEIs and memantine.

    “For patients diagnosed with AD, mixed dementia, and LBD, we further adjusted for ChEIs and memantine.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Premisereasoning

    Existing studies have not thoroughly explored how individual factors, such as age, sex, and dementia severity, may modify the association between antidepressant use and cognitive outcomes.

    “Moreover, existing studies have not thoroughly explored how individual factors, such as age, sex, and dementia severity, may modify the association between antidepressant use and cognitive outcomes.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    A sensitivity analysis among patients with MMSE ≥10 and without depression, excluding patients with baseline severe dementia, was performed to avoid floor effects.

    “Furthermore, to avoid floor effects, we did a sensitivity analysis among patients with MMSE ≥ 10 and without depression, excluding patients with baseline severe dementia.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Study design and conductreasoning

    A competing risk model was applied for outcomes of severe dementia and fracture.

    “Considering the high mortality of patients with dementia after diagnosis, we applied a competing risk model for outcomes of severe dementia and fracture.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The Cause of Death Registry contains data on overall and specific mortality and dates of death.

    “The Cause of Death Registry contains data on overall and specific mortality and dates of death [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] (Socialstyrelsen). NBoHaW. Dödsorsaksregistret Sweden: National Board of Health and Welfare (Socialstyrelsen); 2023. Available from: https://www.socialstyrelsen.se/statistik-och-data/register/dodsorsaksregistret/.

  • Probably not a substantial claim.

    Study design and conductown data

    The beta coefficients and 95% confidence intervals were obtained from adjusted models including age, sex, calendar year of dementia diagnosis, type of dementia, MMSE score at diagnosis, coresident status, type of diagnostic unit, depression, fracture, Charlson Comorbidity Index score, and medications.

    “The beta coefficients (β) and 95% confidence intervals (CIs) were obtained from adjusted models including age, sex, calendar year of dementia diagnosis, the type of dementia, MMSE score at diagnosis, coresident status, type of diagnostic unit, depression, fracture, CCIs, and medications.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Sertraline and escitalopram are first hand choices for depression among older individuals in Sweden.

    “Sertraline and escitalopram are first hand choices for depression among older individuals in Sweden [8].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] committee RSsm. KLOKA LISTAN 2024. Stockholm, Sweden: Stockholm County Council; 2024. Available from: https://klokalistan.se/download/18.2eb60b5b18d2a87a7321b413/1706013022004/Kloka_Listan_2024_webb_20240123.pdf. Cited 2024 03 March.

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

    Premisecitation

    The defined daily dose for each medication is defined by the World Health Organization and was used to allow dose comparisons between different medications.

    “The DDD for each medication is defined by the World Health Organization [35] and was used to allow dose comparisons between different medications.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Organization WH. Defined Daily Dose: Essential Medicines and Health Products: ATC/DDD Toolkit: World Health Organization. Available from: https://www.who.int/toolkits/atc-ddd-toolkit/about-ddd.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

    Premisecitation

    In previous open-label studies in patients with VaD, MMSE score increased significantly in the fluoxetine (SSRI) group but not in the control group.

    “In previous open-label studies in patients with VaD [21], MMSE score increased significantly in the fluoxetine (SSRI) group but not in the control group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Liu X, Zhang J, Sun D, Fan Y, Zhou H, Fu B. Effects of fluoxetine on brain-derived neurotrophic factor serum concentration and cognition in patients with vascular dementia. Clin Interv Aging. 2014;9:411–8.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim. It may be too vague to check against evidence.

    Premisereasoning

    There is a gap in understanding how different antidepressant classes, specific drugs, and doses affect the progression of cognitive decline in patients with dementia.

    “There is a gap in understanding how different antidepressant classes, specific drugs, and doses affect the progression of cognitive decline in patients with dementia.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    In our study, SSRIs were associated with a small negative impact on cognitive functioning, but its clinical significance is uncertain.

    “In our study, we found SSRIs were associated with a small negative impact on cognitive functioning, but its clinical significance is uncertain.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Many patients with dementia seem to have received antidepressant medications for other neuropsychiatric symptoms, as the sensitivity analyses among non-depressed patients did not change the results.

    “However, many patients with dementia seem to have received antidepressant medications for other neuropsychiatric symptoms, as the sensitivity analyses among non-depressed patients did not change the results.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Some of the analyses were imprecisely estimated due to the small number of patients with some individual antidepressants and in stratified analysis.

    “Lastly, some of the analyses were imprecisely estimated due to the small number of patients with some individual antidepressants and in stratified analysis.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Study design and conductown data

    The study did not have information on the severity of depression and actual intake of antidepressants, only dispensation.

    “Furthermore, we did not have information on the severity of depression and actual intake of antidepressants, only dispensation.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductreasoning

    The clinical diagnosis of depression was obtained through specialized in- and out-patient care, which primarily represents more severe manifestations; less severe depression is generally managed through primary care and would have been missed.

    “However, the clinical diagnosis of depression was obtained through specialized in- and out-patient care, which primarily represents more severe manifestations: less severe depression is generally managed through primary care and would have been missed.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductnone given

    Only patients who were new users of antidepressants were included; previous users of antidepressants with depression were not included.

    “In addition, in this study only patients who were new users of antidepressants were included, previous users of antidepressants with depression were not included.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductreasoning

    The severity of dementia could independently contribute to cognitive decline, making it difficult to definitively attribute the observed effects solely to antidepressant use.

    “Third, the severity of dementia could independently contribute to cognitive decline, making it difficult to definitively attribute the observed effects solely to antidepressant use.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Study design and conductown data

    The study repeated and restricted the main analysis to include only patients without depression and found consistent results.

    “To reduce this bias, we repeated and restricted our main analysis to include only patients without depression and found consistent results.”
    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

    Some antidepressants, such as TCAs, are anticholinergic and combining these with acetylcholinesterase inhibitors is counterintuitive due to their conflicting mechanisms of action.

    “Some antidepressants, such as TCAs, are anticholinergic and combining these with acetylcholinesterase inhibitors is counterintuitive due to their conflicting mechanisms of action [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Johnell K, Fastbom J. Concurrent use of anticholinergic drugs and cholinesterase inhibitors: register-based study of over 700,000 elderly patients. Drugs Aging. 2008;25(10):871–7. source

  • Probably not a substantial claim.

    Study design and conductreasoning

    The study calculated and adjusted the inverse probability of censoring weighting to address the issue of selective dropouts.

    “In this study, we calculated and adjusted the inverse probability of censoring weighting to address the issue of selective dropouts.”
    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.

    Study design and conductnone given

    SveDem is a real-world database, which suffers from significant patient loss to follow-up.

    “Fourth, SveDem is a real-world database, which suffers from significant patient loss to follow-up.”
    Quote in the paperNot a substantial claim
44 of 44

  • The authors state this as an assumption.

    A linear trend over time was assumed in the mixed model.

    “Following our previous work in SveDem [36], a linear trend over time was assumed and the model allowed for a random intercept and random slope for each patient.”

  • The paper relies on this without support.

    Antidepressant dispensation data accurately reflect actual antidepressant intake.

    “Furthermore, we did not have information on the severity of depression and actual intake of antidepressants, only dispensation.”

  • The paper relies on this without support.

    Evidence regarding the long-term effect of antidepressants on cognitive decline in VaD is lacking.

    “Evidence regarding the long-term effect of antidepressants on cognitive decline in VaD is lacking.”
3 of 3

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.

  • Five antidepressant classes claimed, but only four listed

    Minor

    The exposure definition says drugs were grouped into five classes but names four. The later analysis likewise identifies only those four classes.

1 of 1

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Organization WH. The ICD-10 classification of mental and behavioural disorders, clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992.

Cited by

Sorted by citations

Related

Metadata

Authors
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.
Affiliations
  • Karolinska Institutet (SE)
  • Sahlgrenska University Hospital (SE)
  • Karolinska University Hospital (SE)
Corresponding author
Mo, Minjia
ORCID
Venue
BMC Medicine
Publisher
Springer Science and Business Media LLC
Published
2025-02-25
Volume
23
Issue
1
Pages
82-82
ISSN
1741-7015 (ISSN-L)
DOI
10.1186/s12916-025-03851-3
PMC
PMC11854023
OpenAlex
W4407895009
Semantic Scholar
51767706a4794fe4ff3f16051b235aa3af4e4ae8
Cited by
45
References
60
Citations by year
2026: 24 · 2025: 20
FWCI
23.43
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Karolinska Institutet Research Foundation (2024-02322)
  • Swedish Research Council for Health, Working Life and Welfare (2024-01295)
  • Swedish Research Council (2022-01428, 2022-01425)
  • StratNeuro start-up grant
  • the Center for Innovative Medicine Foundation (FoUI-963369)
  • Åke Wibergs stiftelse (M22-0170)
  • U&L Angeby stiftelse (2022-02882)
  • KI research foundations
  • Emil and Wera Cornell Foundation
  • Johanniterorden I Sverige/Swedish Order of St. John, Stiftelsen för Sigurd och Elsa Goljes Minne
  • Karolinska Institute
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
cognitive decline, dementia, selective serotonin reuptake inhibitors, escitalopram, sertraline, citalopram, mirtazapine, dose-response relationship, advanced dementia, fracture, mortality, Mini-Mental State Examination, Sweden
MeSH terms
Aged, Aged, 80 and over, Antidepressive Agents, Dementia, Female, Humans, Male, Registries, Sweden, Cohort Studies, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

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