Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression
Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression
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DOI：
10.1038/sj.npp.1300260
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发表时间：
2004-02-01
影响因子：
7.6
通讯作者：
Lee, Y
中科院分区：
文献类型：
--
作者：
Kramer, MS;Winokur, A;Lee, Y
在新化合物证实P物质(NK1)拮抗剂可能提供独特的抗抑郁活性机制后，研究了选择性NK1拮抗剂L-759274在门诊诊断为抑郁症的患者中的有效性和安全性。进行了一项随机、双盲、安慰剂对照研究。患者，男性或女性，年龄18-60岁，21项汉密尔顿抑郁量表(HAMD)前17项总分大于或等于25分，临床总体印象-严重程度量表评分大于或等于4(中度疾病)，随机分为口服L-759274 40环每日40环(n=66)或安慰剂(n=62)，疗程6周。在接受L-759274治疗的患者中，HAMD-17总分的改善(较基线的平均下降)为10.7分，而接受安慰剂的患者的平均改善为7.8点(p<；0.009)。与安慰剂组相比，活动组HAMD-17条目1(抑郁情绪)的平均得分也有更大程度的改善(0.3分，p<；0.058)。与安慰剂相比，临床总体印象-改善量表的平均分数在试验结束时显著改善(p=0.009)。L-759274总体安全，耐受性良好。性副作用的发生率与接受安慰剂的患者持平，胃肠道副作用的发生率很低。现在已经观察到两种不同的高选择性NK1拮抗剂(Approant和L-759274)的抗抑郁作用。NK1拮抗是一种复制的、通常耐受性良好的抗抑郁机制。
The efficacy and safety of a selective NK1 antagonist, L-759274, was investigated in outpatients with diagnosis of major depressive disorder with melancholic features, following evidence obtained with the novel compound aprepitant that Substance P (NK1) antagonists may provide a unique mechanism of antidepressant activity. A randomized, double-blind placebo-controlled study was carried out. Patients, male or female, aged 18-60, scoring greater than or equal to25 points on total of first 17 items of 21-item Hamilton Depression Scale (HAMD), and scoring greater than or equal to4 (moderately ill) on Clinical Global Impressions-Severity Scale were randomized to oral L-759274 40 ring daily (n = 66) or placebo (n 62) for 6 weeks. For patients receiving L-759274, improvement (mean decrease from baseline) in HAMD-17 total score was 10.7 points, compared with a mean 7.8 point improvement in patients receiving placebo (p < 0.009). Mean scores for item 1 of HAMD-17 (depressed mood) also improved to a greater extent in the active group compared with the placebo group (0.3 points, p < 0.058). Compared with placebo, mean scores on Clinical Global Impressions-Improvement Scale improved significantly by the end of the trial (p = 0.009). L-759274 was generally safe and well-tolerated. The incidence of sexual side effects was on par with that observed in patients receiving placebo, and the incidences of gastrointestinal effects were low. Antidepressant actions have now been observed with two different highly selective NK1 antagonists (aprepitant and L-759274). NK1 antagonism is a replicated and generally well-tolerated antidepressant mechanism.