Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial
Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(11)60830-1
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发表时间：
2011-07-01
期刊：
影响因子：
168.9
通讯作者：
Burns, Alistair
中科院分区：
文献类型：
--
作者：
Banerjee, Sube;Hellier, Jennifer;Burns, Alistair
背景抑郁症在痴呆症中很常见，但适当的药物治疗的证据基础是稀疏和模棱两可的。我们的目的是评估两种最常用的处方药物舍曲林和米氮平与安慰剂的疗效和安全性。方法我们在英国9个中心的老年精神病学服务参与者中进行了平行分组、双盲、安慰剂对照的抗抑郁药治疗痴呆的卫生技术评估研究(HTA-SADD)试验。如果参与者有可能或可能患有阿尔茨海默病，抑郁(持续4周)，以及康奈尔痴呆症抑郁量表(CSDD)得分8或更高，就有资格参加。如果参与者临床危急(如自杀风险)，禁忌研究药物，服用抗抑郁药，或在另一项试验中，或没有照顾者，则不符合条件。伦敦国王学院(英国)的临床试验部门通过计算机生成的区组随机序列，按中心分层，按1：1：1的比例随机分配参与者接受舍曲林(目标剂量每天150毫克)、米氮平(45毫克)或安慰剂(对照组)，所有这些都是在标准护理下进行的。主要结果是在13周时抑郁(CSDD评分)的减少(结果也被评估到39周)，通过调整基线CSDD、时间和治疗中心的混合线性回归模型进行评估。这项研究被登记，数字为ISRCTN88882979和EudraCT2006-000105-38。在13周时，111名对照组和107名参与者之间的抑郁得分下降没有差别，这些参与者被分配到服用舍曲林(平均差值1.17，95%CI-0.23至2.58；p=0.10)或米氮平(0.01，-1.37至1.38；p=0.99)，或米氮平组和舍曲林组参与者之间(1.16，-0.25to 2.57；p=0.11)；这些发现持续到39周。与舍曲林组(46/107，43%；p=0.010)或米氮平组(44/108，41%，p=0.031)相比，控制组的不良反应(29/1111，26%)更少，严重不良事件也更少(p=0.003)。每组中有5名患者在39周前死亡。解释：由于与安慰剂相比没有益处，不良事件的风险增加，目前使用这些抗抑郁药，在日常护理下作为阿尔茨海默病抑郁症的一线治疗的做法应该重新考虑。
Background Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.Methods We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting >= 4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at Kings College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38.Findings Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1.17, 95% CI -0.23 to 2.58; p=0.10) or mirtazapine (0.01, -1.37 to 1.38; p=0.99), or between participants in the mirtazapine and sertraline groups (1.16, -0.25 to 2.57; p=0.11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0.010) or mirtazapine group (44 of 108, 41%; p=0.031), and fewer serious adverse events rated as severe (p=0.003). Five patients in every group died by week 39.Interpretation Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer's disease should be reconsidered.