Andrew Sommerlad1,2, Nomi Werbeloff1,2,3, Gayan Perera4,5, Tanya Smith6, Harry Costello7, Christoph Mueller4,5, Andrey Kormilitzin8, Matthew Broadbent5, Alejo Nevado-Holgado8,9, Simon Lovestone9,10, Robert Stewart4,5, Gill Livingston1,2. 1. Division of Psychiatry, University College London, London, UK. 2. Camden and Islington NHS Foundation Trust, London, UK. 3. The Louis and Gabi Weisfeld School of Social Work, Bar Ilan University, Ramat Gan, Israel. 4. Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 5. South London and Maudsley NHS Foundation Trust, London, UK. 6. NIHR Biomedical Research Centre, Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK. 7. Institute of Cognitive Neuroscience, University College London, London, UK. 8. Mathematical Institute, University of Oxford, Oxford, UK. 9. Department of Psychiatry, University of Oxford, Oxford, UK. 10. Johnson and Johnson Medical Ltd., Janssen-Cilag, High Wycombe, UK.
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.
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.
Authors: Emad Sidhom; John T O'Brien; Adrian J Butcher; Heather L Smith; Giovanna R Mallucci; Benjamin R Underwood Journal: Int J Mol Sci Date: 2022-02-11 Impact factor: 5.923
Authors: Emad Sidhom; Mc Stephen Padilla; Jonathan Lewis; Simon White; John T O'Brien; Giovanna R Mallucci; Benjamin R Underwood Journal: Int J Geriatr Psychiatry Date: 2022-08 Impact factor: 3.850