Study protocol for the randomised controlled trial: antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study).
Study protocol for the randomised controlled trial: antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study).
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随机对照试验的研究方案：抗糖皮质激素增强抗抑郁药物治疗抑郁症（ADD 研究）。
DOI：
10.1186/1471-244x-13-205
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发表时间：
2013-08-03
期刊：
影响因子：
4.4
通讯作者：
Ferrier IN
中科院分区：
文献类型：
--
作者：
McAllister-Williams RH;Smith E;Anderson IM;Barnes J;Gallagher P;Grunze HC;Haddad PM;House AO;Hughes T;Lloyd AJ;McColl EM;Pearce SH;Siddiqi N;Sinha B;Speed C;Steen IN;Wainright J;Watson S;Winter FH;Ferrier IN
一些抑郁症患者对一线和二线常规抗抑郁药没有反应，因此被表征为患有难治性抑郁症（TRD）。持续的心理社会压力和下丘脑-垂体-肾上腺轴功能障碍都与抗抑郁药临床反应减弱有关。临床前数据显示，皮质类固醇联合给药导致选择性5-羟色胺再摄取抑制剂增加前脑5-羟色胺的能力降低，而抗糖皮质激素联合给药具有相反的作用。一项科克伦综述表明，抗糖皮质激素增强抗抑郁药可能有效治疗TRD，包括皮质醇合成抑制剂甲吡酮的初步研究。抗糖皮质激素增强抗抑郁药治疗抑郁症（ADD研究）是一项在英国国家卫生服务局的大量TRD患者中进行的甲吡酮增强抗抑郁药治疗的多中心随机安慰剂对照试验。年龄在18至65岁的中重度难治性抑郁症患者将随机接受甲吡酮500 mg每日两次或安慰剂治疗3周，此外还将继续使用常规的苯丙氨酸能抗抑郁药。主要结局将是随机化后5周（即试验药物停药后2周）蒙哥马利-艾斯伯格抑郁评定量表评分的改善。次要结果将包括长达6个月的治疗效果的持续程度，生活质量的改善以及甲吡酮的安全性和耐受性。ADD研究还将包括一系列调查甲吡酮潜在作用机制的子研究。ADD研究的优势包括广泛的入选标准，这意味着样本将代表在英国国家卫生服务体系内接受治疗的TRD患者，更长的随访时间，据我们所知，这比以往任何抗糖皮质激素治疗抑郁症的研究都要长，以及正在进行的机制研究的范围。获得的数据集将是一个丰富的资源，一系列的研究问题，涉及到难治性抑郁症和使用抗糖皮质激素治疗。当前对照试验：ISRCTN 45338259; EudraCT编号：2009 - 015165 - 31。
Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service. Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Åsberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health Service, longer follow up, which to our knowledge is longer than any previous study of antiglucocorticoid treatments in depression, and the range of mechanistic investigations being carried out. The data set acquired will be a rich resource for a range of research questions relating to both refractory depression and the use of antiglucocorticoid treatments. Current Controlled Trials: ISRCTN45338259; EudraCT Number: 2009-015165-31.