A Double-Blind Placebo-Controlled Trial of Lamotrigine as an Antidepressant Augmentation Agent in Treatment-Refractory Unipolar Depression
A Double-Blind Placebo-Controlled Trial of Lamotrigine as an Antidepressant Augmentation Agent in Treatment-Refractory Unipolar Depression
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DOI：
10.4088/jcp.09m05355gre
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发表时间：
2011-10-01
影响因子：
5.3
通讯作者：
Shelton, Richard C.
中科院分区：
文献类型：
--
作者：
Barbee, James G.;Thompson, Thomas R.;Shelton, Richard C.
背景：之前的报告表明，拉莫三嗪作为抗抑郁增强剂，对于治疗难治性单相抑郁症患者是有效的。这项研究是迄今为止拉莫三嗪在这一作用中进行的规模最大的双盲安慰剂对照研究。 方法：在这项在 19 个地点进行的多中心试验中，首先是年龄在 18-65 岁、经 DSM-IV/ICD-10 诊断为单相、非精神病性重度抑郁症（经小型国际神经精神病学访谈证实）且至少 1 次充分的抗抑郁药试验失败的患者 (N=183)。使用开放标签帕罗西汀或帕罗西汀控释剂治疗 8 周，剂量分别高达 50 mg/d 或 62.5 mg/d。然后，汉密尔顿抑郁量表 (HDRS-17) 17 项评分≥ 15 (n=96) 的个体在双盲基础上被随机分配接受安慰剂或拉莫三嗪，剂量逐渐滴定至最大 400 mg/d，持续 10 周。六十五名患者完成了这项研究。主要结局指标是蒙哥马利-阿斯伯格抑郁量表（MADRS），主要的次要结局指标是HDRS-17和临床总体印象-疾病严重程度（CGI-S）和临床总体印象-改善（CGI-1）评级。数据收集自 2003 年至 2006 年。 结果：使用 MADRS、HDRS-17、CGI-S 和 CGI-I 对随机患者进行的主要疗效分析结果并未显示拉莫三嗪组和安慰剂组之间存在统计学显着差异，尽管一些次要分析提示疗效，特别是在完成研究的患者（更完整的分析）和病情较严重的患者中（HDRS-17 >= 25）。 结论：对难治性抑郁症患者进行的附加研究未能检测到服用 10 周的拉莫三嗪和安慰剂之间存在统计学上的显着差异。然而，事后分析表明，未来对拉莫三嗪疗效的研究可能会集中在患有抑郁症的特定亚组上。
Background: Previous reports have suggested that lamotrigine is effective as an antidepressant augmentation agent in patients with treatment-resistant unipolar depression. This study is the largest double-blind placebo-controlled study conducted to date of lamotrigine in this role.Method: In this multicenter trial, conducted at 19 sites, patients aged 18-65 years with a DSM-IV/ICD-10 diagnosis of unipolar, nonpsychotic major depressive disorder (confirmed by the Mini-International Neuropsychiatric Interview) who had failed at least 1 adequate trial of an antidepressant (N=183) were first treated for 8 weeks with open-label paroxetine or paroxetine controlled-release in dosages up to 50 mg/d or 62.5 mg/d, respectively. Individuals with a 17-item Hamilton Depression Rating Scale (HDRS-17) score >= 15 (n=96) were then randomized on a double-blind basis to receive either placebo or lamotrigine in dosages titrated upward to a maximum of 400 mg/d for 10 weeks. Sixty-five patients completed the study. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS), and the main secondary outcome measures were the HDRS-17 and Clinical Global Impressions-Severity of Illness (CGI-S) and Clinical Global Impressions-Improvement (CGI-1) ratings. Data were collected from 2003 to 2006.Results: Results of the primary efficacy analysis of the randomized patients using the MADRS, HDRS-17, CGI-S, and CGI-I did not demonstrate a statistically significant difference between lamotrigine and placebo groups, although some secondary analyses were suggestive of efficacy, particularly in those patients who completed the study (completer analysis) and in more severely ill patients (HDRS-17 >= 25).Conclusions:This add-on study of patients with treatment-resistant depression failed to detect a statistically significant difference between lamotrigine and placebo given for 10 weeks. However, post hoc analyses suggest that future studies of lamotrigine's efficacy might focus on specific subgroups with depression.