Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial,The Lancet

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Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial
The Lancet ( IF 168.9 ) Pub Date : 2021-10-21 , DOI: 10.1016/s0140-6736(21)01210-1
Sube Banerjee ₁ , Juliet High ₂ , Susan Stirling ₂ , Lee Shepstone ₂ , Ann Marie Swart ₂ , Tanya Telling ₃ , Catherine Henderson ₄ , Clive Ballard ₅ , Peter Bentham ₆ , Alistair Burns ₇ , Nicolas Farina ₈ , Chris Fox ₂ , Paul Francis ₅ , Robert Howard ₉ , Martin Knapp ₄ , Iracema Leroi ₁₀ , Gill Livingston ₉ , Ramin Nilforooshan ₁₁ , Shirley Nurock ₁₂ , John O'Brien ₁₃ , Annabel Price ₁₄ , Alan J Thomas ₁₅ , Naji Tabet ₈

Affiliation

Faculty of Health, University of Plymouth, Plymouth, UK.
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK.
Joint Clinical Research Office, University of Sussex, Brighton, UK.
Care Policy and Evaluation Centre, London School of Economics and Political Science, London, UK.
College of Medicine and Health, University of Exeter, Exeter, UK.
Birmingham and Solihull Mental Health Foundation NHS Trust, Birmingham, UK.
University of Manchester, Manchester, UK.
Centre for Dementia Studies, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
Division of Psychiatry, University College London, London, UK.
Department of Psychiatry, Global Brain Health Institute, Trinity College, Dublin, Ireland.
Surrey and Borders Partnership NHS Foundation Trust, Leatherhead, UK.
Former Carer, Alzheimer's Society Research Network, University of Cambridge School of Medicine, Cambridge, UK.
Department of Psychiatry, University of Cambridge School of Medicine, Cambridge, UK.
Cambridgeshire and Peterborough Foundation Trust, Cambridge, UK.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Background

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.

中文翻译：

米氮平治疗痴呆症激越行为的研究 (SYMBAD)：一项随机、双盲、安慰剂对照试验

背景

躁动在痴呆症患者中很常见，会对痴呆症患者和护理人员的生活质量产生负面影响。非药物以患者为中心的护理是一线治疗，但当这种护理无效时，需要其他治疗。目前关于更安全和有效的抗精神病药物替代品的证据很少。我们评估了米氮平的有效性和安全性，米氮平是一种用于治疗痴呆症激越的抗抑郁药。

方法

这项平行组、双盲、安慰剂对照试验——米氮平治疗痴呆症激越行为研究 (SYMBAD)——在英国 26 个中心进行。参与者可能患有或可能患有阿尔茨海默病，躁动对非药物治疗无反应，并且 Cohen-Mansfield 躁动量表 (CMAI) 得分为 45 或更高。他们被随机分配 (1:1) 接受米氮平（滴定至 45 mg）或安慰剂。主要结果是 12 周时 CMAI 评分的降低。该试验已在 ClinicalTrials.gov、NCT03031184 和 ISRCTN17411897 注册。

发现

2017 年 1 月 26 日至 2020 年 3 月 6 日期间，招募并随机分配了 204 名参与者。12 周时的平均 CMAI 评分在接受米氮平的参与者和接受安慰剂的参与者之间没有显着差异（调整后的平均差异 –1·74，95% CI –7·17 至 3·69；p=0·53）。发生不良事件的对照组人数（102 名对照组中的 65 名 [64%]）与米氮平组（接受米氮平的 102 名参与者中的 67 名 [66%]）相似。然而，到第 16 周，米氮平组 (n=7) 的死亡人数高于对照组 (n=1)，事后分析表明这种差异具有边际统计学意义 (p=0·065)。