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

Abstract Background Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia...

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Main Authors: Minjia Mo, Tamar Abzhandadze, Minh Tuan Hoang, Simona Sacuiu, Pol Grau Jurado, Joana B. Pereira, Luana Naia, Julianna Kele, Silvia Maioli, Hong Xu, Maria Eriksdotter, Sara Garcia-Ptacek
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Language:English
Published: BMC 2025-02-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-03851-3
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author Minjia Mo
Tamar Abzhandadze
Minh Tuan Hoang
Simona Sacuiu
Pol Grau Jurado
Joana B. Pereira
Luana Naia
Julianna Kele
Silvia Maioli
Hong Xu
Maria Eriksdotter
Sara Garcia-Ptacek
author_facet Minjia Mo
Tamar Abzhandadze
Minh Tuan Hoang
Simona Sacuiu
Pol Grau Jurado
Joana B. Pereira
Luana Naia
Julianna Kele
Silvia Maioli
Hong Xu
Maria Eriksdotter
Sara Garcia-Ptacek
author_sort Minjia Mo
collection DOAJ
description 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.
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spelling doaj-art-d5853e6f7a994a0c8ed983c204fbe66d2025-08-20T02:16:49ZengBMCBMC Medicine1741-70152025-02-0123111510.1186/s12916-025-03851-3Antidepressant use and cognitive decline in patients with dementia: a national cohort studyMinjia Mo0Tamar Abzhandadze1Minh Tuan Hoang2Simona Sacuiu3Pol Grau Jurado4Joana B. Pereira5Luana Naia6Julianna Kele7Silvia Maioli8Hong Xu9Maria Eriksdotter10Sara Garcia-Ptacek11Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDepartment of Clinical Neurosciences, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDepartment of Laboratory Medicine, Team Neurovascular Biology and Health, Clinical Immunology, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska InstitutetAbstract 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.https://doi.org/10.1186/s12916-025-03851-3DementiaAntidepressantsCognitive declineMortalityCohort
spellingShingle Minjia Mo
Tamar Abzhandadze
Minh Tuan Hoang
Simona Sacuiu
Pol Grau Jurado
Joana B. Pereira
Luana Naia
Julianna Kele
Silvia Maioli
Hong Xu
Maria Eriksdotter
Sara Garcia-Ptacek
Antidepressant use and cognitive decline in patients with dementia: a national cohort study
BMC Medicine
Dementia
Antidepressants
Cognitive decline
Mortality
Cohort
title Antidepressant use and cognitive decline in patients with dementia: a national cohort study
title_full Antidepressant use and cognitive decline in patients with dementia: a national cohort study
title_fullStr Antidepressant use and cognitive decline in patients with dementia: a national cohort study
title_full_unstemmed Antidepressant use and cognitive decline in patients with dementia: a national cohort study
title_short Antidepressant use and cognitive decline in patients with dementia: a national cohort study
title_sort antidepressant use and cognitive decline in patients with dementia a national cohort study
topic Dementia
Antidepressants
Cognitive decline
Mortality
Cohort
url https://doi.org/10.1186/s12916-025-03851-3
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