University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh PA, USA.
Neuropsychiatr Dis Treat. 2009;5:563-76. doi: 10.2147/ndt.s5453. Epub 2009 Nov 16.
This article describes the pharmacology of the novel atypical antidepressant drug agomelatine, critically reviews and evaluates its clinical use for the treatment of major depression, and suggests areas for further research. Agomelatine is a synthetic analog of the hormone melatonin. It stimulates the activity of melatonin MT1 and MT2 receptors and inhibits the activity of serotonin 5HT-2C receptor subtypes. Three acute trials demonstrated clinically modest, but statistically significant benefits over placebo. Three acute trials did not find agomelatine more effective than placebo. A meta-analysis of these six trials demonstrated a small, statistically significant, marginally clinically relevant difference between agomelatine and placebo. The only placebo-controlled study in elderly patients did not demonstrate a significant benefit for agomelatine. It was more effective than placebo in only one of two relapse prevention studies. Agomelatine was generally well tolerated compared to placebo. Its side-effect profile is different than and compares favorably to other antidepressant drugs. The overall tolerability of agomelatine in head-to-head comparisons was not substantially better than active drug comparators. Agomelatine is contraindicated in patients with impaired liver function and in patients taking drugs that potently inhibit CYP-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. Agomelatine does not have clinically significant advantages compared to other antidepressant drugs, and it has certain limitations and disadvantages. Because of its unique pharmacology and relatively benign tolerability profile, however, it may be a useful alternative for patients who do not respond to or cannot tolerate other antidepressant drugs.
本文描述了新型非典型抗抑郁药阿戈美拉汀的药理学，批判性地回顾和评估了其在治疗重性抑郁症方面的临床应用，并提出了进一步研究的领域。阿戈美拉汀是褪黑素激素的合成类似物。它刺激褪黑素 MT1 和 MT2 受体的活性，并抑制 5HT-2C 受体亚型的活性。三项急性试验表明，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。三项急性试验未发现阿戈美拉汀比安慰剂更有效。这六项试验的荟萃分析表明，阿戈美拉汀与安慰剂之间存在微小但统计学显著的、临床相关的差异。在老年患者中进行的唯一安慰剂对照研究并未显示阿戈美拉汀有显著益处。在两项预防复发的研究中，它仅在一项研究中比安慰剂更有效。与安慰剂相比，阿戈美拉汀通常具有更好的耐受性。其副作用谱与其他抗抑郁药不同，且具有优势。在头对头比较中，阿戈美拉汀的总体耐受性与活性药物对照剂相比并没有明显改善。阿戈美拉汀禁用于肝功能受损的患者和正在服用强力抑制 CYP-1A2 代谢酶的药物的患者。由于肝酶升高很常见，且存在更严重肝反应的罕见风险，因此建议在整个治疗过程中定期进行常规实验室监测肝功能。与其他抗抑郁药相比，阿戈美拉汀并没有明显的临床优势，而且它有一定的局限性和缺点。然而，由于其独特的药理学和相对良性的耐受性，对于那些对其他抗抑郁药无反应或不能耐受的患者，它可能是一种有用的替代药物。
