Volume 29, Issue 161, July 2025

Melatonin as a prophylactic treatment for migraine - A systematic review of literature

Julia Sztubińska^1♦, Marta Tortyna², Marta Urszula Marciniak³, Danuta Borowska⁴, Julia Urbańska⁵, Paula Szarek⁶, Olga Samsel⁷, Natalia Sioch⁸, Julia Krotofil⁹, Maciej Trzciński¹⁰, Kamil Nieczaj¹¹

¹Faculty of Medicine, Medical University of Gdańsk, Poland
²Faculty of Medicine, Medical University of Gdańsk, Poland
³Faculty of Medicine, Medical University of Gdańsk, Poland
⁴Faculty of Medicine, Medical University of Gdańsk, Poland
⁵Faculty of Medicine, Medical University of Gdańsk, Poland
⁶Faculty of Medicine and Health Sciences, Collegium Medicum of the University of Zielona Góra, Zielona Góra, Poland
⁷Faculty of Medicine, Medical University of Gdańsk, Poland
⁸Faculty of Medicine, Medical University of Gdańsk, Poland
⁹Faculty of Medicine, Medical University of Gdańsk, Poland
¹⁰Faculty of Medicine, Medical University of Gdańsk, Poland
¹¹Faculty of Medicine, Medical University of Gdańsk, Poland

^♦Corresponding author
Julia Sztubińska; Faculty of Medicine, Medical University of Gdańsk, Poland

ABSTRACT

Migraine is one of the most common widespread neurological conditions. Even though we have access to a variety of treatment options, such as beta-blockers, anticonvulsants, and antidepressants, their tolerability is often limited because of their side effects. Recently a well known neurohormone - melatonin, which is responsible for regulating the sleep-wake cycle, became the subject of research as a potential alternative to standard therapeutic options. In this systematic review we have concluded the results of the studies published between 2015 and 2024. We focused on the efficacy, safety, and tolerability of melatonin in comparison to valproic acid and amitriptyline. The results consistently demonstrate that melatonin decreases migraine frequency and severity. Furthermore, it lowers the reliance on pain medication. Its efficacy is generally comparable to valproic acid and slightly lower than amitriptyline but melatonin presents fewer and milder side effects making it more tolerable. The fact that melatonin alleviates both headache symptoms and sleep disturbances may play a key role in its selection as a treatment for a particular group of patients. Studies involving pediatric populations suggest that melatonin may be a safe and beneficial option also for children, although further evidence is required. The findings of this review support the thesis that melatonin might be a promising, safe, well-tolerated, and accessible option in migraine management. However, more clinical trials are needed to establish treatment guidelines and determine the most effective dosage and duration of melatonin treatment.

Keywords: Migraine, Melatonin, Migraine prophylaxis, Valproic acid, Amitriptyline

Medical Science, 2025, 29, e120ms3621

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DOI: https://doi.org/10.54905/disssi.v29i161.e120ms3621

Published: 30 July 2025