Abstract
The availability and use of melatonin as an over-the-counter supplement have surged significantly in recent years due to the increased prevalence of sleep-wake disorders, notably in the post-COVID-19 era. While melatonin is known for managing insomnia, its applications extend beyond that. Its anti-inflammatory, antioxidant, and analgesic properties, along with increased usage, have garnered significant interest from researchers, particularly regarding its use in migraine prophylaxis and treatment. The aim of this systematic review is to evaluate the role of melatonin as prophylactic therapy for migraine, focusing on the efficacy and side effect profile of melatonin compared to standard therapy and placebo. Six databases were searched through June 2024, identifying 735 relevant articles. Only full-text randomized control trials involving humans, written or translated into English, were included in the study. Data were extracted, screened, sought for retrieval, and assessed for quality appraisal using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). A total of seven randomized control trials involving 1,283 participants who met the eligibility criteria and passed the quality appraisal have been included in the study. All seven trials included patients diagnosed with migraine who were treated with either melatonin or agomelatine and were compared to those treated with conventional prophylactic therapy or placebo. The findings of this review suggest that melatonin significantly reduces the frequency and severity of migraines, but its dose-dependent action and benefits remain debatable. Melatonin may also have a role in weight control, warranting additional research in this direction.