Bottemanne H, Claret A, Fossati P
Control-Interoception-Attention team, Paris Brain Institute, Institut du Cerveau (ICM), UMR 7225/UMR_S 1127, Sorbonne University/CNRS/Inserm, Paris, France.; Department of Psychiatry, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Department of Psychiatry, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (APHP), Paris, France.
Encephale. 2021 Apr;47(2):171-178. doi: 10.1016/j.encep.2020.08.006. Epub 2020 Nov 12.
The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has provoked a renewed interest in hallucinogenic substances such as psilocybin targeting the serotonergic signaling 5HT and neurosteroid allosteric modulator of γ-aminobutyric acid (GABAA) receptors such as brexanolone. Unlike conventional treatments, these modulators of glutamatergic, serotonergic and GABAergic systems exert a rapid antidepressant effect ranging from 24hours to a week. Apart from their clinical interest and the fantasized search for a "miracle" molecule that jointly meets the expectations of patients and clinicians, these new targets could lead to the identification of potential new biomarkers for the development of rapid-acting antidepressants and redefine therapeutic strategies in mood disorders.
单胺能缺乏假说长期以来一直主导着新抗抑郁策略开发的概念框架，但针对单胺能信号传导的传统抗抑郁治疗的局限性促使人们寻找新的抗抑郁途径。氯胺酮在治疗抑郁症方面的成功引发了人们对致幻物质（如靶向5-羟色胺信号传导5HT的裸盖菇素）以及γ-氨基丁酸（GABAA）受体的神经甾体变构调节剂（如布雷沙诺龙）的新兴趣。与传统治疗不同，这些谷氨酸能、5-羟色胺能和GABA能系统的调节剂具有从24小时到一周不等的快速抗抑郁作用。除了它们的临床意义以及对共同满足患者和临床医生期望的“神奇”分子的幻想式探索之外，这些新靶点可能会促成快速起效抗抑郁药开发中潜在新生物标志物的识别，并重新定义情绪障碍的治疗策略。
