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Lookup NU author(s): Dr Clive Ballard, Professor Alan ThomasORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. Methods: This parallel-group, double-blind, placebo-controlled trial—the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)—was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. Findings: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference –1·74, 95% CI –7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). Interpretation: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. Funding: UK National Institute for Health Research Health Technology Assessment Programme.
Author(s): Banerjee S, High J, Stirling S, Shepstone L, Swart AM, Telling T, Henderson C, Ballard C, Bentham P, Burns A, Farina N, Fox C, Francis P, Howard R, Knapp M, Leroi I, Livingston G, Nilforooshan R, Nurock S, O'Brien J, Price A, Thomas AJ, Tabet N
Publication type: Article
Publication status: Published
Journal: The Lancet
Year: 2021
Volume: 398
Issue: 10310
Pages: 1487-1497
Print publication date: 23/10/2021
Online publication date: 21/10/2021
Acceptance date: 02/04/2021
Date deposited: 09/11/2023
ISSN (print): 0140-6736
ISSN (electronic): 1474-547X
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/S0140-6736(21)01210-1
DOI: 10.1016/S0140-6736(21)01210-1
Data Access Statement: Deidentified participant data will be available with investigator support from 9 months after publication of the final project reports via sube.banerjee@plymouth.ac.uk by researchers whose proposed use of the data has been approved by the Trial Management Committee for meta-analyses or analyses that have been approved. The trial protocol can be found in the appendix p 3).
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