Treatment Research Center, Department of Psychiatry, Rush University Medical Center, Chicago, IL 60612, USA.
J Clin Psychopharmacol. 2010 Apr;30(2):135-44. doi: 10.1097/JCP.0b013e3181d420a7.
In this 8-week double-blind multicenter trial, we evaluated the efficacy and safety of 2 fixed doses of agomelatine in patients with moderate to severe major depressive disorder. Primary efficacy variable was the change in 17-item Hamilton Depression Rating Scale (HAM-D17) total score from baseline to week 8/end of treatment. Secondary efficacy assessment compared the improvements in clinical response and remission (HAM-D17), Clinical Global Impression--Improvement Score, Clinical Global Impression--Severity Score, Hospital Anxiety and Depression (HAD), sleep (Leeds Sleep Evaluation Questionnaire), disability (Sheehan Disability Scale), and overall Quality of Life in Depression Scale between the agomelatine and placebo groups. Eligible patients (n = 511; baseline mean HAM-D17 score = 27.0) were randomized (1:1:1) to once-daily agomelatine, 25 mg; agomelatine, 50 mg; or placebo. Agomelatine 50 mg provided a statistically significant improvement in HAM-D17 score from first baseline visit through week 8 compared with placebo (week 8 treatment difference, 2.5; P = 0.004), whereas agomelatine 25 mg did not show (P = 0.505) a significant improvement. Treatment differences for all secondary efficacy variables were also statistically significant for agomelatine 50 mg versus placebo: Clinical Global Impression--Improvement (P = 0.012); Clinical Global Impression--Severity difference (P = 0.003); improvement in HAD total score, 2.2 (P = 0.014); patients' ability to get sleep (P < 0.001); quality of sleep (P = 0.002). Both doses of agomelatine were well tolerated relative to placebo. However, clinically notable transient aminotransferase elevations were observed in 4.5% of the patients in the agomelatine 50 mg group. The results showed significant antidepressant efficacy of agomelatine 50 mg/d, including a positive effect on sleep compared with placebo in outpatients with moderate to severe major depressive disorder.
在这项为期 8 周的双盲、多中心试验中，我们评估了 2 种固定剂量的阿戈美拉汀在中重度重性抑郁障碍患者中的疗效和安全性。主要疗效变量是从基线到第 8 周/治疗结束时 17 项汉密尔顿抑郁量表（HAM-D17）总分的变化。次要疗效评估比较了阿戈美拉汀和安慰剂组在临床反应和缓解（HAM-D17）、临床总体印象-改善评分、临床总体印象-严重程度评分、医院焦虑和抑郁量表（HAD）、睡眠（利兹睡眠评估问卷）、残疾（希恩残疾量表）和抑郁总体生活质量量表方面的改善。符合条件的患者（n = 511；基线 HAM-D17 评分平均= 27.0）按 1:1:1 随机分配至每日一次阿戈美拉汀 25 mg、阿戈美拉汀 50 mg 或安慰剂。与安慰剂相比，阿戈美拉汀 50 mg 治疗第 8 周时 HAM-D17 评分有统计学意义的改善（第 8 周治疗差异为 2.5；P = 0.004），而阿戈美拉汀 25 mg 未显示（P = 0.505）显著改善。阿戈美拉汀 50 mg 与安慰剂相比，所有次要疗效变量的治疗差异也具有统计学意义：临床总体印象-改善（P = 0.012）；临床总体印象-严重程度差异（P = 0.003）；HAD 总分改善 2.2（P = 0.014）；患者入睡能力（P < 0.001）；睡眠质量（P = 0.002）。与安慰剂相比，阿戈美拉汀的两种剂量均具有良好的耐受性。然而，在阿戈美拉汀 50 mg 组的 4.5%的患者中观察到临床显著的短暂性转氨酶升高。结果表明，阿戈美拉汀 50 mg/d 具有显著的抗抑郁疗效，包括与安慰剂相比，对中重度重性抑郁障碍门诊患者的睡眠有积极影响。
