The Role of Melatonin in the Treatment of Primary Headache Disorders

Abstract

Objective: To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders. Background: Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness. Methods: We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders. Results: There are randomized placebo-controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo-controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin's role in treating tension-type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache. Conclusions: Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation.