A multisite trial of mifepristone for the treatment of psychotic depression: A site-by-treatment interaction
A multisite trial of mifepristone for the treatment of psychotic depression: A site-by-treatment interaction
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DOI：
10.1016/j.cct.2009.03.001
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发表时间：
2009-07-01
影响因子：
2.2
通讯作者：
Belanoff, Joseph K.
中科院分区：
文献类型：
--
作者：
Blasey, Christine M.;DeBattista, Charles;Belanoff, Joseph K.
具有精神病特征的重度抑郁症（精神病性抑郁症）是一种常见的使人衰弱的精神疾病。我们假设，米非司酮，皮质醇受体（GRII）拮抗剂，将显着减少精神病性抑郁症的精神病性症状。258例精神病性抑郁症患者在29个网站注册随机米非司酮或安慰剂7天。主要结局是快速和持续的反应，定义为治疗结束时（第7天）和49天后（第56天）简明精神病评定量表阳性症状子量表评分下降50%或以上。Cochran-Mantel-Haenszel比较了米非司酮与安慰剂的反应者比例，并根据研究中心进行了调整。探索性分析比较了米非司酮血药浓度>= 1800 ng/ml患者与安慰剂的反应，主要终点无统计学意义。然而，Breslow-Day检验表明中心-治疗相互作用具有统计学显著性。米非司酮在20个试验点中产生了显著更高的反应（p= 1800 ng/ml），比安慰剂患者更有可能产生反应（意向治疗：OR=2.4，p= 0.03;初始20个试验点：OR=4.1，p= 0.002）。首先，虽然在多中心临床试验中统计调整部位是常见的，但本研究提醒试验者正式评估治疗部位的相互作用。第二，米非司酮血浆浓度水平升高与临床反应增强之间的相关性（尽管存在治疗部位间的相互作用）表明，可能需要更高的血浆浓度才能使阳性反应的概率最大化。(C)2009 Elsevier Inc. All rights reserved.
Major Depression with Psychotic Features (psychotic depression) is a common, debilitating psychiatric disease. We hypothesized that mifepristone, a cortisol receptor (GRII) antagonist, would significantly reduce psychotic symptoms in psychotic depression.Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were randomized to mifepristone or placebo for 7 days. The primary outcome was rapid and sustained response, defined as a 50% or greater decrease in Brief Psychiatric Rating Scale Positive Symptom Subscale scores at the end of treatment (day7) and 49 days later (day 56). Cochran-Mantel-Haenszel compared proportions of responders to mifepristone versus placebo adjusting for site. Exploratory analyses compared response of patients with mifepristone plasma concentrations of >= 1800 ng/ml to placebo.The primary endpoint was not statistically significant. However, the Breslow-Day test indicated a statistically significant site-by-treatment interaction. Mifepristone produced significantly higher response among the twenty sites who participated from the trial onset (p= 1800 ng/ml were significantly more likely to respond than placebo patients (Intent-to-Treat: OR=2.4, p=.03; Initial 20 sites: OR=4.1, p=.002).The results of this trial are instructive in two respects. First, while statistical adjustment site are common in multisite clinical trials, this study reminds trialists to formally evaluate the interaction of site-by-treatment. Second, the association between increased mifepristone plasma concentration levels and greater clinical response, detected despite the site-by-treatment interaction, suggests that higher plasma levels may be needed for maximizing the probability of a positive response. (C) 2009 Elsevier Inc. All rights reserved.