Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data

Andrew Sommerlad; Nomi Werbeloff; Gayan Perera; Tanya Smith; Harry Costello; Christoph Mueller; Andrey Kormilitzin; Matthew  Broadbent; Alejo Nevado‐Holgado; Simon Lovestone; Robert Stewart; Gill Livingston

doi:10.1002/gps.5625

Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data

Andrew Sommerlad, Nomi Werbeloff, Gayan Perera, Tanya Smith, Harry Costello, Christoph Mueller, Andrey Kormilitzin, Matthew Broadbent, Alejo Nevado‐Holgado, Simon Lovestone, Robert Stewart, Gill Livingston

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Abstract

Objectives: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. Methods: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008–16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. Results: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03–0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses. Conclusions: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.

Original language	English
Journal	International Journal of Geriatric Psychiatry
Volume	37
Issue number	1
Early online date	4 Oct 2021
DOIs	https://doi.org/10.1002/gps.5625
Publication status	Published - Jan 2022

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10.1002/gps.5625

Sommerlad Trazodone 2021Licence: CC BY

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Sommerlad, A., Werbeloff, N., Perera, G., Smith, T., Costello, H., Mueller, C., Kormilitzin, A., Broadbent, M., Nevado‐Holgado, A., Lovestone, S., Stewart, R., & Livingston, G. (2022). Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data. International Journal of Geriatric Psychiatry, 37(1). https://doi.org/10.1002/gps.5625

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title = "Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data",

abstract = "Objectives: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. Methods: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008–16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. Results: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03–0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses. Conclusions: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.",

author = "Andrew Sommerlad and Nomi Werbeloff and Gayan Perera and Tanya Smith and Harry Costello and Christoph Mueller and Andrey Kormilitzin and Matthew Broadbent and Alejo Nevado‐Holgado and Simon Lovestone and Robert Stewart and Gill Livingston",

note = "Funding Information: Andrew Sommerlad is funded by the Wellcome Trust (200163/Z/15/Z). Andrew Sommerlad, Nomi Werbeloff, Harry Costello and Gill Livingston were supported by the University College London Hospitals National Institute of Health Research (NIHR) Biomedical Research Centre (BRC). Gayan Perera, Christoph Mueller, Matthew Broadbent and Robert Stewart are part‐funded by the NIHR BRC at South London and Maudsley NHS Foundation Trust and King's College London. SLaM CRIS is supported by the NIHR BRC for Mental Health BRC Nucleus at the SLaM NHS Foundation Trust and Institute of Psychiatry, King's College London jointly funded by the Guy's and St Thomas' Trustees and the SLaM Trustees. Oxford CRIS is supported by the NIHR BRC at Oxford Health NHS Foundation trust. We acknowledge funding for the CRIS system from NIHR and from NIHR and MRC as part of Dementias Platform UK. The authors analysed results and prepared this manuscript independently of the funding bodies. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, MRC, NIHR or the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Andrew Sommerlad is funded by the Wellcome Trust (200163/Z/15/Z). Andrew Sommerlad, Nomi Werbeloff, Harry Costello and Gill Livingston were supported by the University College London Hospitals National Institute of Health Research (NIHR) Biomedical Research Centre (BRC). Gayan Perera, Christoph Mueller, Matthew Broadbent and Robert Stewart are part-funded by the NIHR BRC at South London and Maudsley NHS Foundation Trust and King's College London. SLaM CRIS is supported by the NIHR BRC for Mental Health BRC Nucleus at the SLaM NHS Foundation Trust and Institute of Psychiatry, King's College London jointly funded by the Guy's and St Thomas' Trustees and the SLaM Trustees. Oxford CRIS is supported by the NIHR BRC at Oxford Health NHS Foundation trust. We acknowledge funding for the CRIS system from NIHR and from NIHR and MRC as part of Dementias Platform UK. The authors analysed results and prepared this manuscript independently of the funding bodies. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, MRC, NIHR or the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.",

year = "2022",

month = jan,

doi = "10.1002/gps.5625",

language = "English",

volume = "37",

journal = "International Journal of Geriatric Psychiatry",

issn = "0885-6230",

publisher = "WILEY-BLACKWELL",

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Sommerlad, A, Werbeloff, N, Perera, G, Smith, T, Costello, H, Mueller, C, Kormilitzin, A, Broadbent, M, Nevado‐Holgado, A, Lovestone, S , Stewart, R & Livingston, G 2022, 'Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data', International Journal of Geriatric Psychiatry, vol. 37, no. 1. https://doi.org/10.1002/gps.5625

TY - JOUR

T1 - Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data

AU - Sommerlad, Andrew

AU - Werbeloff, Nomi

AU - Perera, Gayan

AU - Smith, Tanya

AU - Costello, Harry

AU - Mueller, Christoph

AU - Kormilitzin, Andrey

AU - Broadbent, Matthew

AU - Nevado‐Holgado, Alejo

AU - Lovestone, Simon

AU - Stewart, Robert

AU - Livingston, Gill

N1 - Funding Information: Andrew Sommerlad is funded by the Wellcome Trust (200163/Z/15/Z). Andrew Sommerlad, Nomi Werbeloff, Harry Costello and Gill Livingston were supported by the University College London Hospitals National Institute of Health Research (NIHR) Biomedical Research Centre (BRC). Gayan Perera, Christoph Mueller, Matthew Broadbent and Robert Stewart are part‐funded by the NIHR BRC at South London and Maudsley NHS Foundation Trust and King's College London. SLaM CRIS is supported by the NIHR BRC for Mental Health BRC Nucleus at the SLaM NHS Foundation Trust and Institute of Psychiatry, King's College London jointly funded by the Guy's and St Thomas' Trustees and the SLaM Trustees. Oxford CRIS is supported by the NIHR BRC at Oxford Health NHS Foundation trust. We acknowledge funding for the CRIS system from NIHR and from NIHR and MRC as part of Dementias Platform UK. The authors analysed results and prepared this manuscript independently of the funding bodies. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, MRC, NIHR or the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Andrew Sommerlad is funded by the Wellcome Trust (200163/Z/15/Z). Andrew Sommerlad, Nomi Werbeloff, Harry Costello and Gill Livingston were supported by the University College London Hospitals National Institute of Health Research (NIHR) Biomedical Research Centre (BRC). Gayan Perera, Christoph Mueller, Matthew Broadbent and Robert Stewart are part-funded by the NIHR BRC at South London and Maudsley NHS Foundation Trust and King's College London. SLaM CRIS is supported by the NIHR BRC for Mental Health BRC Nucleus at the SLaM NHS Foundation Trust and Institute of Psychiatry, King's College London jointly funded by the Guy's and St Thomas' Trustees and the SLaM Trustees. Oxford CRIS is supported by the NIHR BRC at Oxford Health NHS Foundation trust. We acknowledge funding for the CRIS system from NIHR and from NIHR and MRC as part of Dementias Platform UK. The authors analysed results and prepared this manuscript independently of the funding bodies. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, MRC, NIHR or the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

PY - 2022/1

Y1 - 2022/1

N2 - Objectives: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. Methods: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008–16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. Results: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03–0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses. Conclusions: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.

AB - Objectives: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. Methods: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008–16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. Results: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03–0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses. Conclusions: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.

UR - http://www.scopus.com/inward/record.url?scp=85116104771&partnerID=8YFLogxK

U2 - 10.1002/gps.5625

DO - 10.1002/gps.5625

M3 - Article

SN - 0885-6230

VL - 37

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

IS - 1

ER -

Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data

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