Goodwin Guy M, Emsley Robin, Rembry Sandra, Rouillon Frédéric
Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford, United Kingdom OX3 7JX, UK.
J Clin Psychiatry. 2009 Aug;70(8):1128-37. doi: 10.4088/JCP.08m04548. Epub 2009 Aug 11.
This study evaluates the efficacy of agomelatine, the first antidepressant that is an agonist at MT(1)/MT(2) receptors and an antagonist at 5-HT(2C) receptor, in the prevention of relapse of depression following successful response.
Patients with DSM-IV-TR major depressive disorder who responded to an 8- or 10-week course of agomelatine 25- or 50-mg daily treatment were randomly assigned to receive continuation treatment with agomelatine (n=165) or placebo (n=174) during a 24-week, randomized, double-blind treatment period. The main outcome measure was time to relapse during the double-blind treatment period. The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis. The study was conducted from February 2005 to February 2007.
During the 6-month evaluation period, the incidence of relapse was significantly lower in patients who continued treatment than in those switched to placebo (P=.0001). The cumulative relapse rate at 6 months for agomelatine-treated patients was 21.7%; that for placebo-treated patients was 46.6%. Agomelatine was also superior to placebo in preventing relapse in the subset of patients with baseline 17-item Hamilton Depression Rating Scale total score > or = 25. Measures of tolerability and safety of both doses of agomelatine were similar to placebo. No pattern of early relapse or adverse events suggestive of withdrawal symptoms was obtained after abrupt cessation of agomelatine.
The findings are important in 2 respects. First, agomelatine is an effective and safe antidepressant continuation therapy, which confirms efficacy seen in short-term studies. Second, few early relapses were observed in the patient group switched to placebo: the survival curve for placebo separated gradually from that of patients taking agomelatine. We suggest this reflects solely the underlying properties of the illness, which is only possible due to the lack of discontinuation syndrome after agomelatine withdrawal. It underlines the novel clinical profile of agomelatine, which quite likely reflects its innovative pharmacology.
isrctn.org Identifier: ISRCTN53193024.
本研究评估阿戈美拉汀（第一种既是褪黑素1型/褪黑素2型（MT(1)/MT(2)）受体激动剂又是5-羟色胺2C型（5-HT(2C)）受体拮抗剂的抗抑郁药）在成功治疗后预防抑郁症复发的疗效。
对接受为期8周或10周、每日25毫克或50毫克阿戈美拉汀治疗且有反应的DSM-IV-TR重度抑郁症患者，在24周的随机双盲治疗期内随机分配接受阿戈美拉汀（n = 165）或安慰剂（n = 174）继续治疗。主要结局指标是双盲治疗期内的复发时间。复发的累积概率采用Kaplan-Meier生存分析方法计算。该研究于2005年2月至2007年2月进行。
在6个月的评估期内，继续治疗的患者复发率显著低于换用安慰剂的患者（P = 0.0001）。阿戈美拉汀治疗患者6个月时的累积复发率为21.7%；安慰剂治疗患者为46.6%。在基线17项汉密尔顿抑郁量表总分≥25分的患者亚组中，阿戈美拉汀在预防复发方面也优于安慰剂。两种剂量阿戈美拉汀的耐受性和安全性指标与安慰剂相似。突然停用阿戈美拉汀后，未观察到提示撤药症状的早期复发或不良事件模式。
这些发现有两方面的重要意义。第一，阿戈美拉汀是一种有效且安全的抗抑郁延续治疗药物，证实了短期研究中的疗效。第二，换用安慰剂的患者组中观察到的早期复发很少：安慰剂的生存曲线逐渐与服用阿戈美拉汀的患者的生存曲线分离。我们认为这仅反映了疾病的潜在特性，这仅因阿戈美拉汀撤药后缺乏撤药综合征才有可能。这突出了阿戈美拉汀独特的临床特征，很可能反映了其创新的药理学特性。
isrctn.org标识符：ISRCTN53193024。
