University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA, USA.
Drug Saf. 2011 Sep 1;34(9):709-31. doi: 10.2165/11593960-000000000-00000.
Agomelatine is an antidepressant drug that is a synthetic analogue of the hormone melatonin. It stimulates the activity of melatonin MT(1) and MT(2) receptors and inhibits the activity of serotonin 5HT(2C) receptor subtypes. The objective of this article is to critically review and evaluate the benefits and risks of agomelatine for the treatment of major depression. The published literature through April 2011 for articles relating to agomelatine, together with unpublished data on agomelatine available from the European Medicines Agency, the US FDA, US ClinicalTrials.gov and the Novartis Clinical Trial Results Database are reviewed. The antidepressant efficacy of agomelatine has been systematically assessed in ten short-term, placebo-controlled studies and three longer-term, placebo-controlled, relapse prevention studies. Five short-term trials demonstrated clinically modest, but statistically significant, benefits over placebo, although two of these studies reported opposite effects for 25 mg versus 50 mg doses. The other five short-term trials did not find agomelatine more effective than placebo, but in two of these studies the active control drug was more effective than placebo. A meta-analysis of six European trials demonstrated a small, statistically significant, marginally clinically relevant difference in efficacy favouring agomelatine over placebo. The only placebo-controlled study in elderly patients did not demonstrate a significant benefit for agomelatine. Agomelatine was shown to be more effective than placebo in one of three relapse prevention studies. Agomelatine was generally well tolerated compared with placebo. Its adverse effect profile is different to that of other antidepressant drugs, but its overall tolerability in studies with other antidepressants as active control drugs did not appear to be substantially better than the controls. Agomelatine is contraindicated in patients with impaired liver function and in patients taking drugs that potently inhibit cytochrome P450 1A2 metabolic enzymes. Because elevated liver enzymes are common, and there is a rare risk of more serious liver reactions, routine laboratory monitoring of liver function is recommended periodically throughout treatment. Based on this comprehensive review, agomelatine does not have clinically significant advantages compared with other antidepressant drugs, and it has certain limitations and disadvantages. Because of the unique pharmacology of agomelatine and its reported tolerability profile, it should only be considered as an alternative drug for patients who do not respond to or cannot tolerate other antidepressant drugs.
阿戈美拉汀是一种抗抑郁药，是激素褪黑素的合成类似物。它刺激褪黑素 MT(1)和 MT(2)受体的活性，抑制血清素 5HT(2C)受体亚型的活性。本文的目的是批判性地评价和评估阿戈美拉汀治疗重度抑郁症的益处和风险。通过 2011 年 4 月之前发表的与阿戈美拉汀相关的文献，以及欧洲药品管理局、美国食品药品监督管理局、美国 ClinicalTrials.gov 和诺华临床试验结果数据库中未发表的阿戈美拉汀数据进行了回顾。阿戈美拉汀的抗抑郁疗效已在十项短期安慰剂对照研究和三项长期安慰剂对照复发预防研究中得到系统评估。五项短期试验显示，与安慰剂相比，阿戈美拉汀具有临床适度但统计学显著的益处，尽管其中两项研究报告了 25mg 和 50mg 剂量的相反效果。其他五项短期试验未发现阿戈美拉汀比安慰剂更有效，但其中两项研究表明活性对照药物比安慰剂更有效。六项欧洲试验的荟萃分析表明，阿戈美拉汀在疗效上优于安慰剂，差异虽小，但具有统计学意义，在临床相关方面略有优势。唯一一项在老年患者中进行的安慰剂对照研究并未显示阿戈美拉汀有显著益处。在三项复发预防研究中的一项研究中，阿戈美拉汀比安慰剂更有效。与安慰剂相比，阿戈美拉汀通常具有良好的耐受性。其不良影响谱与其他抗抑郁药不同，但在其他抗抑郁药作为活性对照药物的研究中，其总体耐受性似乎并没有明显优于对照药物。肝功能受损的患者和正在服用强力抑制细胞色素 P450 1A2 代谢酶的药物的患者禁用阿戈美拉汀。由于肝酶升高很常见，而且存在更严重肝反应的罕见风险，建议在整个治疗过程中定期进行肝功能的常规实验室监测。基于这一全面审查，阿戈美拉汀与其他抗抑郁药相比并没有明显的临床优势，而且它存在一定的局限性和缺点。由于阿戈美拉汀独特的药理学特性及其报告的耐受性特征，它仅应被视为对其他抗抑郁药无反应或不能耐受的患者的替代药物。
