"Melatonin 3 mg was significantly better than placebo with no difference compared to amitriptyline with respect to migraine prevention," principal investigator Mario Peres, MD, PhD, told delegates here attending the American Academy of Neurology (AAN) 65th Annual Meeting.
"But if we look at the proportion of responders, then melatonin had better results than amitriptyline," added Dr. Peres, who is director of São Paulo Headache Center, professor of neurology at ABC Medical School, and senior research associate at the Albert Einstein Brain Research Institute, Brazil.
According to Dr. Peres
, melatonin's role in regulating circadian rhythm has been linked to cluster headache, hypnic headache, and migraine.
noted, melatonin plays an important role in sleep regulation, and disruption of melatonin production has been linked to sleep disorders, including sleep apnea, insomnia, and delayed sleep phase syndrome, which, in turn, are linked to headache.
also noted that there is a bidirectional relationship in which headache can disrupt sleep and lead to insomnia and excessive daytime sleepiness.
pointed out that research has linked low levels of melatonin in plasma and urine and altered peak time in melatonin levels to a variety of headache types, including migraine.
According to Dr. Peres
, research into melatonin as a potential treatment for headache has included several case reports and open-label studies but only 2 randomized controlled trials: 1 in cluster headache, which was positive, and 1 negative trial in migraine.
The negative migraine trial, he
said, had several limitations, including a small sample size and a short duration of only 8 weeks.
Melatonin was also "very tolerable" and had significantly fewer adverse effects compared with amitriptyline, said Dr. Peres
Daytime sleepiness was the most frequent symptom in all 3 groups but was most pronounced in the amitriptyline group (n = 24).
Although patients gained weight in both the amitriptyline (n = 3) and placebo (n = 1) groups, melatonin was associated with weight loss.
Timing of administration and formulation is also important.
Ideally, said Dr. Peres
, melatonin should be taken between 10 pm and 11 pm to mimic the physiologic peak.
In addition, a fast-acting rather than a slow-release formula should be used.
Overall, said Dr. Peres
, the study's findings are promising and warrant further research.
and Dr. Kurth have disclosed no relevant financial relationships.