Centre de Recherches sur la Cognition Animale, Centre de Biologie Intégrative, Université de Toulouse, CNRS, 31000, Toulouse, France.
Département de psychiatrie, CHU Toulouse-Purpan, Toulouse NeuroImaging Center, ToNIC, Université de Toulouse, Inserm, 31059, Toulouse, France.
Psychopharmacology (Berl). 2022 Sep;239(9):2735-2752. doi: 10.1007/s00213-022-06203-8. Epub 2022 Aug 10.
Major depression (MD) is one of the most common psychiatric disorders worldwide. Currently, the first-line treatment for MD targets the serotonin system but these drugs, notably the selective serotonin reuptake inhibitors, usually need 4 to 6 weeks before the benefit is felt and a significant proportion of patients shows an unsatisfactory response. Numerous treatments have been developed to circumvent these issues as venlafaxine, a mixed serotonin-norepinephrine reuptake inhibitor that binds and blocks both the SERT and NET transporters. Despite this pharmacological profile, it is difficult to have a valuable insight into its ability to produce more robust efficacy than single-acting agents. In this review, we provide an in-depth characterization of the pharmacological properties of venlafaxine from in vitro data to preclinical and clinical efficacy in depressed patients and animal models of depression to propose an indirect comparison with the most common antidepressants. Preclinical studies show that the antidepressant effect of venlafaxine is often associated with an enhancement of serotonergic neurotransmission at low doses. High doses of venlafaxine, which elicit a concomitant increase in 5-HT and NE tone, is associated with changes in different forms of plasticity in discrete brain areas. In particular, the hippocampus appears to play a crucial role in venlafaxine-mediated antidepressant effects notably by regulating processes such as adult hippocampal neurogenesis or the excitatory/inhibitory balance. Overall, depending on the dose used, venlafaxine shows a high efficacy on depressive-like symptoms in relevant animal models but to the same extent as common antidepressants. However, these data are counterbalanced by a lower tolerance. In conclusion, venlafaxine appears to be one of the most effective treatments for treatment of major depression. Still, direct comparative studies are warranted to provide definitive conclusions about its superiority.
重度抑郁症（MD）是全球最常见的精神障碍之一。目前，MD 的一线治疗方法针对的是 5-羟色胺系统，但这些药物，尤其是选择性 5-羟色胺再摄取抑制剂，通常需要 4 到 6 周才能见效，而且相当一部分患者的反应并不理想。为了规避这些问题，已经开发出许多治疗方法，如文拉法辛，一种混合性 5-羟色胺-去甲肾上腺素再摄取抑制剂，能结合并阻断 SERT 和 NET 转运体。尽管具有这种药理学特性，但要深入了解其产生比单作用药物更强大疗效的能力仍然很困难。在这篇综述中，我们从体外数据到临床前和临床疗效，深入描述了文拉法辛的药理学特性，以评估其与最常见的抗抑郁药的间接比较。临床前研究表明，文拉法辛的抗抑郁作用通常与低剂量时增强 5-羟色胺能神经传递有关。高剂量的文拉法辛会同时增加 5-HT 和 NE 张力，与不同脑区不同形式的可塑性变化有关。特别是，海马似乎在文拉法辛介导的抗抑郁作用中起着关键作用，特别是通过调节成年海马神经发生或兴奋性/抑制性平衡等过程。总的来说，根据使用的剂量，文拉法辛在相关动物模型中对抑郁样症状显示出很高的疗效，但与常见的抗抑郁药的疗效相同。然而，这些数据被耐受性较差所抵消。总之，文拉法辛似乎是治疗重度抑郁症的最有效治疗方法之一。然而，仍需要进行直接比较研究，以提供关于其优越性的明确结论。
