Pierz Kerri A, Thase Michael E
Clinical Data, Inc, New Haven, Connecticut (Dr Pierz), and Perelman School of Medicine, University of Pennsylvania, Philadelphia (Dr Thase). Dr Pierz is now with Purdue Pharma, Stamford, Connecticut.
Prim Care Companion CNS Disord. 2014;16(1). doi: 10.4088/PCC.13r01554. Epub 2014 Jan 9.
To review the mechanism of selective serotonin reuptake inhibitor (SSRI)-mediated serotonergic neurotransmission, focusing on serotonin 1A (5-HT1A) autoreceptors, which are proposed to be involved in delaying therapeutic efficacy. Vilazodone was specifically designed to function both as an SSRI and a partial agonist at 5-HT1A receptors. This combined mechanism is proposed to decrease time to efficacy, minimize sexual side effects, and provide concomitant anxiolytic properties.
A PubMed search of all English-language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT 1A, depression and buspirone, depression and pindolol, and vilazodone.
We found 47 articles and abstracts that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol, buspirone, and vilazodone in depression.
This review summarizes current literature involving antidepressant activity, the role of 5-HT1A autoreceptors, and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists, with a focus on vilazodone.
Vilazodone has demonstrated efficacy in 2 large, randomized, double-blind, placebo-controlled trials in major depressive disorder. RESULTS suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety. A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy.
If future studies corroborate the clinical benefits attributed to its mechanism of action, vilazodone may show potential advantages in terms of onset of action, sexual side effects, and anxiolytic activity in patients with major depressive disorder.
回顾选择性5-羟色胺再摄取抑制剂（SSRI）介导的5-羟色胺能神经传递机制，重点关注5-羟色胺1A（5-HT1A）自身受体，该受体被认为与治疗疗效延迟有关。伏硫西汀被特意设计成兼具SSRI和5-HT1A受体部分激动剂的功能。这种联合机制被认为可缩短起效时间、将性副作用降至最低，并具有协同抗焦虑特性。
使用搜索词“抑郁症与5-HT 1A”“抑郁症与丁螺环酮”“抑郁症与吲哚洛尔”以及“伏硫西汀”，对1990年1月至2013年1月期间所有英文文章进行了PubMed检索。
我们发现47篇文章和摘要，这些文章和摘要基于有关5-HT1A受体药理学以及丁螺环酮、吲哚洛尔和伏硫西汀在抑郁症方面的临床数据而被选入。
本综述总结了当前涉及抗抑郁活性、5-HT1A自身受体作用以及5-HT1A激动剂和部分激动剂联合5-羟色胺再摄取抑制的临床试验的文献，重点是伏硫西汀。
伏硫西汀在两项针对重度抑郁症的大型随机双盲安慰剂对照试验中已证明具有疗效。结果表明伏硫西汀性副作用发生率低，对焦虑水平高的患者有效。一项汇总分析显示，仅治疗1周后就有显著症状减轻的证据。
如果未来研究证实其作用机制所带来的临床益处，那么伏硫西汀在重度抑郁症患者的起效时间、性副作用和抗焦虑活性方面可能会显示出潜在优势。
