Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Health Research Institute, Clinical Pharmacology Service, University Hospital La Princesa, Autonomous University of Madrid, C/ Diego de León 62, 28006 Madrid, Spain; Institute Teófilo Hernando for Drug I+D, School of Medicine, Autonomous University of Madrid, 28029 Madrid, Spain.
Toxicol Appl Pharmacol. 2020 Apr 1;392:114933. doi: 10.1016/j.taap.2020.114933. Epub 2020 Feb 26.
There is a lack of effective therapies for stroke patients; its treatment is even more difficult considering the unexpected onset of the disease. In the last decade, melatonin has emerged as a promising neuroprotective agent which is able to cross the blood-brain-barrier (BBB) and with a low toxicity profile. The aim of this systematic review was to summarize and critically review clinical and pre-clinical evidence related to melatonin's effectiveness as a stroke treatment. Together with a comparative dose extrapolation with those used in the selected randomized controlled trials (RCTs), and based on these data to discuss whether the administered doses correlate with those advisable in human patients. To address this purpose, we performed a systematic review of the available literature. A total of 529 records were screened with the selecting of six full articles containing RCTs that met the inclusion/exclusion criteria. The evidence drawn from these six reports was analyzed to identify remaining gaps, treatment efficacy, and to suggest future directions. The primary outcome reported was the reduction of the oxidative response; the secondary outcome was the increase of the survival rate of the patients in the intervention groups. Calculations derived from animal studies revealed that the translational doses to humans were substantially higher than those employed in the RCTs. The findings of this systematic review revealed that there are insufficient RCTs to prove melatonin's value in stroke patients. Nevertheless, the evidence is promising, and further clinical research may support the benefits of melatonin in stroke patients, if the adequate dose is administered.
目前针对脑卒中患者缺乏有效的治疗方法，由于脑卒中发病突然，其治疗更加困难。在过去的十年中，褪黑素作为一种有前途的神经保护剂出现了，它能够穿透血脑屏障（BBB）且具有低毒性。本系统评价的目的是总结和批判性地回顾与褪黑素作为脑卒中治疗有效性相关的临床和临床前证据。我们与选定的随机对照试验（RCT）中使用的剂量进行了比较外推，并基于这些数据来讨论所给予的剂量是否与人类患者中的建议剂量相关。为了达到这个目的，我们对现有的文献进行了系统评价。共筛选了 529 条记录，选择了 6 篇符合纳入/排除标准的包含 RCT 的全文。对这 6 份报告中的证据进行了分析，以确定存在的差距、治疗效果，并提出未来的方向。报告的主要结果是减少氧化反应；次要结果是干预组患者的生存率增加。从动物研究中得出的计算结果表明，转化为人类的剂量远远高于 RCT 中使用的剂量。本系统评价的结果表明，目前 RCT 不足以证明褪黑素对脑卒中患者的价值。然而，证据是有希望的，如果给予适当的剂量，进一步的临床研究可能会支持褪黑素对脑卒中患者的益处。
