Melatonin is a neuroregulator hormone that has free radical scavenger, strong antioxidant, anti-inflammatory, and immunosuppressive actions. These major properties of melatonin can play an important role in the pathophysiological mechanisms of neurological diseases. (Gunata et al, 2019)
Melatonin may have a role in the biological regulation of circadian rhythms, sleep, mood, and ageing. Altered melatonin levels in cluster headache and migraine have been documented. Melatonin mechanisms are related to headache pathophysiology in many ways, including its anti-inflammatory effect, toxic free radical scavenging, reduction of proinflammatory cytokine up-regulation, nitric oxide synthase activity and dopamine release inhibition, membrane stabilization, GABA and opioid analgesia potentiation, glutamate neurotoxicity protection, neurovascular regulation, serotonin modulation, and the similarity of chemical structure to that of indomethacin. (Peres, 2005)
Some headaches have a clearcut seasonal and circadian pattern, such as cluster and hypnic headaches. Melatonin levels have been found to be decreased in both migraine and cluster headaches. (Peres et al, 2006)
Melatonin showed a beneficial prophylactic role in migraine, with a better responder rate in comparison to placebo in reducing migraine severity, mean attack duration, mean attack frequency, and analgesic use, but did not show significant effects in comparison to amitriptyline or valproate. (Puliappadamb et al, 2022)
Gunata M, Parlakpinar H, Acet HA. Melatonin: A review of its potential functions and effects on neurological diseases. Rev Neurol (Paris). 2020 Mar;176(3):148-165. doi: 10.1016/j.neurol.2019.07.025. Epub 2019 Nov 11. PMID: 31718830.
Peres MF. Melatonin, the pineal gland and their implications for headache disorders. Cephalalgia. 2005 Jun;25(6):403-11. doi: 10.1111/j.1468-2982.2005.00889.x. PMID: 15910564.
Peres MF, Masruha MR, Zukerman E, Moreira-Filho CA, Cavalheiro EA. Potential therapeutic use of melatonin in migraine and other headache disorders. Expert Opin Investig Drugs. 2006 Apr;15(4):367-75. doi: 10.1517/13543784.15.4.367. PMID: 16548786.
Puliappadamb HM, Maiti R, Mishra A, Jena M, Mishra BR. Efficacy and Safety of Melatonin as Prophylaxis for Migraine in Adults: A Meta-analysis. J Oral Facial Pain Headache. 2022 Summer;36(3-4):207–219. doi: 10.11607/ofph.3211. Epub 2022 Nov 28. PMID: 36445912; PMCID: PMC10586587.