Kansai Medical University, Graduate School of Medicine, iPS Cell Applied Medicine, Hirakata, Osaka, Japan.
University of Alabama at Birmingham, Department of Psychiatry and Behavioral Neurobiology, Birmingham, AL, USA; Biomedical Sciences Institute, Department of Human Physiology, Sao Paulo University, Sao Paulo, Brazil.
Drug Discov Today. 2023 Dec;28(12):103804. doi: 10.1016/j.drudis.2023.103804. Epub 2023 Oct 20.
Pharmacological treatment of major depressive disorder (MDD) still relies on the use of serotonergic drugs, despite their limited efficacy. A few mechanistically new drugs have been developed in recent years, but many fail in clinical trials. Several hypotheses have been proposed to explain MDD pathophysiology, indicating that physiological processes such as neuroplasticity, circadian rhythms, and metabolism are potential targets. Here, we review the current state of pharmacological treatments for MDD, as well as the preclinical and clinical evidence for an antidepressant effect of molecules that target non-serotonergic systems. We offer some insights into the challenges facing the development of new antidepressant drugs, and the prospect of finding more effectiveness for each target discussed.
抗抑郁障碍（MDD）的药物治疗仍然依赖于使用 5-羟色胺能药物，尽管它们的疗效有限。近年来开发了一些机制上的新型药物，但许多药物在临床试验中失败。已经提出了几种假设来解释 MDD 的病理生理学，表明神经可塑性、昼夜节律和代谢等生理过程可能是潜在的靶点。在这里，我们回顾了 MDD 的药物治疗现状，以及针对非 5-羟色胺能系统的分子具有抗抑郁作用的临床前和临床证据。我们对开发新型抗抑郁药物所面临的挑战以及针对每个讨论靶点寻找更高疗效的前景提供了一些见解。
