New antidepressants: New day or false dawn?
New antidepressants: New day or false dawn?
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新的抗抑郁药：新的一天还是虚假的黎明？
DOI：
10.1016/j.euroneuro.2022.07.004
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Jelen LA
中科院分区：
文献类型：
--
作者：
Jelen LA
自20世纪80年代以来，选择性血清素再摄取抑制剂（SSRIs）的引入，直到世纪之交，抑郁症的药理学治疗才出现新的突破。这种情况随着偶然发现单次亚麻醉剂量的解离性氯胺酮（n -甲基- d -天冬氨酸（NMDA）谷氨酸受体拮抗剂）可以诱导抑郁症状迅速显著减轻而改变；这一发现在许多治疗难治性单极和双相抑郁症的临床研究中得到了重复（jellen和Stone， 2021）。这使得抑郁症研究从专注于单胺能神经传递缺陷转向探索替代生物靶点，包括谷氨酸能和gaba能系统，作为下一代治疗的有希望的途径。基于氯胺酮快速抗抑郁作用的证据，研究人员探索了其他几种NMDA受体拮抗剂是否与氯胺酮具有相同的抗抑郁特性，然而，其他几种NMDA受体拮抗剂和NMDA受体位点调节剂（如美金刚、GLYX-13、CERC-301）的临床研究未能产生令人信服的结果。右美沙芬-安非他酮（AXS-05）是一种口服NMDA受体拮抗剂和sigma-1受体拮抗剂，最近的一项3期研究显示，在抑郁症状和缓解诱导方面，右美沙芬-安非他酮（AXS-05）的前景更大（Iosifescu等，2022）。AXS-05用于治疗重度抑郁症（MDD）的新药申请正在接受美国食品和药物管理局（FDA）的审查。
Following the introduction of the selective serotonin reuptake inhibitors (SSRIs) from the 1980s onwards, there were no new breakthrough pharmacological treatments for depression until the turn of the millennium. This changed with the serendipitous discovery that a single sub-anaesthetic dose of the dissociative ketamine, a N-Methyl-D-Aspartate (NMDA) glutamate receptor antagonist, could induce rapid and significant reductions in depressive symptoms; a finding since replicated in numerous clinical studies in treatment-resistant unipolar and bipolar depression (Jelen and Stone, 2021). This has taken depression research away from a focus on targeting deficits in monoaminergic neurotransmission towards an exploration of alternative biological targets, including the glutamatergic and GABAergic systems, as promising avenues for next-generation treatments.Building on evidence for the rapid antidepressant effects of ketamine, investigators have explored whether alternative NMDA receptor antagonists may share ketamine’s antidepressant properties, however clinical studies of several other NMDA receptor antagonists and NMDA receptor site modulators (eg, memantine, GLYX-13, CERC-301) have failed to produce convincing results. More promise has been seen with dextromethorphan-bupropion (AXS-05), an oral NMDA receptor antagonist and sigma-1 receptor antagonist, with a recent phase 3 study demonstrating rapid, substantial, and statistically significant improvement in depressive symptoms and induction of remission (Iosifescu et al., 2022). A new drug application for AXS-05 for the treatment of major depressive disorder (MDD) is under review by the US Food and Drug Administration (FDA).
影响因子：
168.9
作者：
Meltzer-Brody, Samantha;Colquhoun, Helen;Kanes, Stephen
通讯作者：
Kanes, Stephen
影响因子：
17.7
作者：
McIntyre, Roger S.;Rosenblat, Joshua D.;Nemeroff, Charles B.;Sanacora, Gerard;Murrough, James W.;Berk, Michael;Brietzke, Elisa;Dodd, Seetal;Gorwood, Philip;Ho, Roger;Iosifescu, Dan, V;Jaramillo, Carlos Lopez;Kasper, Siegfried;Kratiuk, Kevin;Lee, Jung Goo;Lee, Yena;Lui, Leanna M. W.;Mansur, Rodrigo B.;Papakostas, George, I;Subramaniapillai, Mehala;Thase, Michael;Vieta, Eduard;Young, Allan H.;Zarate, Carlos A., Jr.;Stahl, Stephen
通讯作者：
Stahl, Stephen