Melatonin supplementation may benefit patients with acute ischemic stroke not eligible for reperfusion therapies: Results of a pilot study

We explored the potential efficacy of melatonin in the treatment of patients with acute ischemic stroke.This double-blind, placebo-controlled single-center clinical trial was conducted on 65 patients with acute ischemic stroke not eligible for reperfusion therapy. All patients received routine acute stroke management. Melatonin and placebo were administrated orally at a dose of 20 mg once daily for five days. The severity of neurological deficit and stroke-related functional disability was assessed on the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale score (mRS), respectively, on days 5, 30, and 90 after treatment.All patients completed the 5-day treatment period, and no serious adverse event was observed. While on day 5, the neurological status and stroke-related functional disability were comparable in both groups, on days 30 and 90, melatonin treatment resulted in a higher reduction in the median NIHSS and mRS score than placebo. Moreover, the overall changes in the NIHSS and mRS scores through a three-month follow-up assessment were significantly greater in the melatonin group than in the placebo group. The analysis of NIHSS scores distribution on day 90 showed a significant difference between the study groups in favor of the melatonin treatment. However, in relation to the functional independence criteria, defined as an mRS < 3, there were no significant differences between the groups at different study time points.Although preliminary, our findings support the hypothesis that early treatment with melatonin may be helpful in improving functional and neurological recovery following stroke.The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N378). Registration date: 2021-01-28.