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of viloxazine based on information from previously published preclinical and clinical investigations, and acquired unpublished historical study reports from both open-label and blinded controlled clinical trials.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.

维洛嗪在欧洲作为抗抑郁药具有悠久的临床使用历史，最近在美国被重新制成缓释剂型，用于治疗注意力缺陷/多动症。1974 年，一种速释制剂在英国被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（例如三环类抗抑郁药、单胺氧化酶抑制剂）相比，维洛嗪的心脏毒性风险相对较低。胃肠道症状是最常见的副作用。维洛嗪的治疗效果被认为主要是其作为去甲肾上腺素再摄取抑制剂的作用的结果，尽管体外和临床前体内动物数据表明维洛嗪也可能影响血清素能系统。本综述根据先前发表的临床前和临床研究的信息总结了维洛嗪的不断发展的知识，并从开放标签和盲法对照临床试验中获取了未发表的历史研究报告。我们回顾了这些研究的化学性质、作用机制、安全性和耐受性，并讨论了开发这种药物作为缓释口服制剂用于治疗注意力缺陷/多动症的当代基本原理。