The Therapeutic Potential of Melatonin in Migraines and other Headache Types

Alternative Medicine Review, August, 2001 by Joel J. Gagnier

Melatonin Administration and Migraine

A small study by Claustrat et al looked at noctumal plasma melatonin profile and melatonin kinetics during melatonin infusion in migraine patients.[35] The study consisted of 15 female patients: six current headache sufferers and nine healthy controls. The two groups were matched for age and fertility. In this open trial all 15 patients received a saline solution between 8 p.m. and 1 a.m. on the first night ([N.sub.0]) and melatonin infusions of 20 ug at 4 ug per hour (9 p.m. to 1 a.m.) the next three nights ([N.sub.1],[N.sub.2],[N.sub.3]). Blood was sampled between 8 p.m. and 8 a.m. at 20-minute intervals. Individual plasma profiles were disturbed in three migraine patients; two had a phase-delay (a late maximum plasma melatonin level) and one a phase-advance (an early maximum plasma melatonin level). Although four of the six headache patients had increased plasma melatonin, basal melatonin levels were relatively similar between groups. With infusion, two patients with previous phase delay demonstrated a phase advance in melatonin profile.

The authors suggest this finding, together with previous research, supports the hypothesis that melatonin may help in the resynchronization of biological rhythms. Four of the six patients reported headache relief the morning after melatonin infusion began and the remaining two patients did so after the third night of infusion. In addition, three patients described that during migraines there was a decrease in the pulsatility of pain. The authors state such symptomatic improvement could be due to any number of the biochemical actions of melatonin: resetting the biological rhythm, relieving anxiety and insomnia, inhibiting prostaglandin synthesis, inhibiting nitric oxide synthesis, depressing calcium uptake, or directly affecting cerebral blood vessels via receptor sites. Although this study was neither blinded nor placebo controlled, melatonin profile changes and symptomatic relief following melatonin infusion support the hypothesis that migraines may be related to a melatonin profile abnormality, and that melatonin administration may be therapeutically indicated in such patients.

Another study investigated the effects of melatonin on varying headaches and their relation to delayed sleep phase syndrome (DSPS).[36] A control melatonin profile was taken in each patient prior to administration of exogenous melatonin. This double-blind, placebo-controlled, cross-over study randomly assigned 30 patients to a placebo group or a 5 mg melatonin group for 14 days, after which they were crossed-over for an additional 14 days. Patients received melatonin for at least three months following the initial 28-day period. Patients were questioned about their headaches at 2 weeks, and 3, 6, 9, and 12 months. A 54-year-old man with DSPS, who had migraine attacks without aura since childhood and twice per week the past five years, reported having only three migraines during the 12 months after beginning melatonin treatment. In addition, one patient with previous cluster headaches of two months duration twice per year for twenty years reported only one headache in the 12 months since beginning treatment. In three patients with chronic tension-type headaches complete disappearance of headaches occurred within two weeks of treatment.