VCU Department of Psychiatry, 501 North 2nd Street, Richmond, VA, 23298-0308, USA.
Supernus Pharmaceuticals, Inc., Rockville, MD, USA.
CNS Drugs. 2021 Jun;35(6):643-653. doi: 10.1007/s40263-021-00825-w. Epub 2021 May 18.
Viloxazine has a long history of clinical use in Europe as an antidepressant, and has recently been repurposed into an extended-release form for the treatment of attention-deficit/hyperactivity disorder in the USA. An immediate-release formulation was approved for the treatment of depression in the UK in 1974, and was subsequently marketed there and in several European countries for 30 years with no major safety concerns. In contrast to first-generation antidepressants (e.g., tricyclic antidepressants, monoamine oxidase inhibitors), viloxazine was associated with a relatively low risk for cardiotoxicity. Gastrointestinal symptoms were the most commonly reported side effects. The therapeutic effects of viloxazine are thought to be primarily the result of its action as a norepinephrine reuptake inhibitor, although in vitro and preclinical in vivo animal data suggest that viloxazine may also impact the serotoninergic system. This review summarizes the evolving knowledge of viloxazine based on information from previously published preclinical and clinical investigations, and acquired unpublished historical study reports from both open-label and blinded controlled clinical trials. We review the chemical properties, mechanism of action, safety, and tolerability across these studies, and discuss the contemporary rationale for the development of this agent as an extended-release oral formulation for the treatment of attention-deficit/hyperactivity disorder.
维洛沙嗪在欧洲作为一种抗抑郁药已有很长的临床应用历史，最近在美国被重新开发为一种用于治疗注意力缺陷/多动障碍的缓释形式。1974 年，一种即刻释放制剂在英国获得批准用于治疗抑郁症，随后在英国和几个欧洲国家销售了 30 年，没有出现重大安全问题。与第一代抗抑郁药（如三环类抗抑郁药、单胺氧化酶抑制剂）不同，维洛沙嗪与较低的心脏毒性风险相关。胃肠道症状是最常见的不良反应。维洛沙嗪的治疗效果主要被认为是其作为去甲肾上腺素再摄取抑制剂的作用结果，尽管体外和临床前动物数据表明，维洛沙嗪也可能影响 5-羟色胺能系统。本综述基于先前发表的临床前和临床研究以及开放标签和盲法对照临床试验的未发表历史研究报告，总结了维洛沙嗪的最新知识。我们回顾了这些研究中的化学特性、作用机制、安全性和耐受性，并讨论了将该药物开发为用于治疗注意力缺陷/多动障碍的缓释口服制剂的当代原理。
