Ionescu D F, Papakostas G I
Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Transl Psychiatry. 2017 Mar 21;7(3):e1068. doi: 10.1038/tp.2017.33.
Depression is one of the most common psychiatric conditions. Symptoms can lead to significant disability, which result in impairments in overall quality of life. Though there are many approved antidepressant treatments for depression-including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors-about a third of patients do not respond to these medications. Therefore, it is imperative for drug discovery to continue towards the development of novel and rapidly acting compounds, especially for patients with treatment-resistant depression. After a brief review of the efficacy of approved antidepressant therapies, we will discuss experimental medication treatments for depression. Specifically, we examine novel medications that are thought to primarily modulate the glutamatergic, cholinergic and opioid systems to achieve antidepressant efficacy. We also give examples of anti-inflammatories, neurokinin-1 modulators, vasopressin antagonists and neurogenesis enhancers that may have a therapeutic role in treatment-resistant depression. The current pipeline of antidepressant treatments is shifting towards medications with novel mechanisms, which may lead to important, life-changing discoveries for patients with severe disease.
抑郁症是最常见的精神疾病之一。症状可导致严重的功能障碍，进而影响整体生活质量。尽管有许多已获批用于治疗抑郁症的抗抑郁药物，包括选择性5-羟色胺再摄取抑制剂、三环类抗抑郁药和单胺氧化酶抑制剂，但约三分之一的患者对这些药物无反应。因此，继续研发新型速效化合物对于药物发现至关重要，尤其是对于难治性抑郁症患者。在简要回顾已获批抗抑郁疗法的疗效后，我们将讨论抑郁症的实验性药物治疗。具体而言，我们将研究那些被认为主要通过调节谷氨酸能、胆碱能和阿片样物质系统来实现抗抑郁疗效的新型药物。我们还将举例说明抗炎药、神经激肽-1调节剂、血管加压素拮抗剂和神经发生增强剂，它们可能在难治性抑郁症治疗中发挥治疗作用。目前抗抑郁治疗的研发方向正转向具有新机制的药物，这可能会为重症患者带来重要的、改变生活的发现。
