Major depression: emerging therapeutics.
Major depression: emerging therapeutics.
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DOI：
10.1002/msj.20043
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发表时间：
2008-06
期刊：
影响因子：
--
通讯作者：
S. Sen;G. Sanacora
中科院分区：
文献类型：
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作者：
S. Sen;G. Sanacora
第一种有效的抗抑郁药物，单胺氧化酶抑制剂和三环抗抑郁药，是在50年前被发现的，主要是通过偶然发现的。这些药物被发现在长期使用几周后能改善略多于一半的抑郁症患者的情绪。今天开出的几乎所有抗抑郁药都是通过对这些原始抗抑郁药进行轻微修改而开发出来的，与单胺氧化酶抑制剂和三环类抗抑郁药一样，主要通过单胺能机制发挥作用。虽然副作用和过量用药的毒性有所改善，但这些新药并没有在患者的抗抑郁疗效和起效速度方面取得实质性进展。在过去的20年里，我们对抑郁症背后的神经生物学的了解呈指数级增长。鉴于这种扩张，我们可能正接近抗抑郁药物开发的拐点，在这个拐点上，通过对生物系统的理性理解，将设计出有用的药物。在这篇综述中，我们讨论了一系列有前景的抗抑郁药物的生物学基础以及临床前和临床证据，这些药物主要是从病理生理信息的方法开发出来的。
The first effective antidepressants, monoamine oxidase inhibitors and tricyclic antidepressants, were identified 50 years ago, largely through serendipity. These medications were found to improve mood in a little more than half of depressed patients after a few weeks of chronic use. Almost all antidepressants prescribed today were developed through minor modifications of these original antidepressants and, like monoamine oxidase inhibitors and tricyclic antidepressants, act primarily through monoaminergic mechanisms. Although there have been improvements in side-effect profiles and overdose toxicity, these newer medications have not provided substantial advances in the efficacy and speed of the antidepressant effect for patients. Over the last 2 decades, our understanding of the neurobiology underlying depression has expanded exponentially. Given this expansion, we may be nearing an inflection point in antidepressant drug development, at which useful medicines will be designed through a rational understanding of the biological systems. In this review, we discuss the biological basis and preclinical and clinical evidence for a series of promising classes of antidepressants developed primarily out of a pathophysiologically informed approach.