Servei de Psiquiatría, Hospital de Sant Pau, Universidat Autonoma de Barcelona, Barcelona, Spain.
Int J Neuropsychopharmacol. 2012 Jun;15(5):589-600. doi: 10.1017/S1461145711001027. Epub 2011 Jul 18.
The efficacy, safety, and tolerability of Lu AA21004 vs. placebo using venlafaxine XR as active reference in patients with DSM-IV-TR major depressive disorder (MDD) were evaluated. Lu AA21004 is a novel antidepressant that is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. In this 6-wk, multi-site study, 429 patients were randomly assigned (1:1:1:1) to 5 or 10 mg Lu AA21004, placebo or 225 mg venlafaxine XR. All patients had a baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 30. The primary efficacy analysis was based on the MADRS total score adjusting for multiplicity using a hierarchical testing procedure starting with the highest dose vs. placebo. Lu AA21004 was statistically significantly superior to placebo (n=105) in mean change from baseline in MADRS total score at week 6 (p<0.0001, last observation carried forward), with a mean treatment difference vs. placebo of 5.9 (5 mg, n=108), and 5.7 (10 mg, n=100) points. Venlafaxine XR (n=112) was also significantly superior to placebo at week 6 (p<0.0001). In total, 30 patients withdrew due to adverse events (AEs)--placebo: four (4%); 5 mg Lu AA21004: three (3%); 10 mg Lu AA21004: seven (7%); and venlafaxine: 16 (14%). The most common AEs were nausea, headache, hyperhidrosis, and dry mouth. No clinically relevant changes over time were seen in the clinical laboratory results, vital signs, weight, or ECG parameters. In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD.
Lu AA21004 与安慰剂相比，使用文拉法辛 XR 作为活性参照，在符合 DSM-IV-TR 重性抑郁障碍（MDD）标准的患者中的疗效、安全性和耐受性。Lu AA21004 是一种新型抗抑郁药，它是 5-HT3 和 5-HT7 受体拮抗剂、5-HT1A 受体激动剂、5-HT1B 受体部分激动剂和 5-HT 转运体的抑制剂，在重组细胞系中。在这项为期 6 周的多地点研究中，429 名患者被随机分配（1:1:1:1）接受 5 或 10 mg Lu AA21004、安慰剂或 225 mg 文拉法辛 XR。所有患者的基线 Montgomery-Åsberg 抑郁评定量表（MADRS）总分≥30。主要疗效分析基于 MADRS 总分，采用分层检验程序，从最高剂量与安慰剂相比开始，对多重性进行调整。Lu AA21004 在第 6 周时与基线相比，MADRS 总分的平均变化明显优于安慰剂（n=105，p<0.0001，最后一次观察向前推进），与安慰剂相比，治疗差异分别为 5.9（5 mg，n=108）和 5.7（10 mg，n=100）点。文拉法辛 XR（n=112）在第 6 周时也明显优于安慰剂（p<0.0001）。共有 30 名患者因不良事件（AE）而退出研究（安慰剂：4%，n=4；5 mg Lu AA21004：3%，n=3；10 mg Lu AA21004：7%，n=7；文拉法辛：14%，n=16）。最常见的 AE 是恶心、头痛、多汗和口干。在临床试验结果、生命体征、体重或心电图参数方面，没有随时间出现临床相关的变化。在这项研究中，5 mg 和 10 mg Lu AA21004 治疗 6 周，在 MDD 患者中是有效且耐受良好的。
