BOSTON—Compared with placebo, a 3-mg dose of melatonin reduces the number of headache days that a patient with migraine has per month, according to research presented at the 2013 International Headache Congress. Although melatonin may be associated with a greater reduction in the number of headache days per month than amitriptyline is, the difference is not statistically significant.
Compared with patients taking amitriptyline, a larger number of patients taking melatonin had a reduction in headache frequency of more than 50%, said Andre Leite Gonçalves, MD, PhD, Research Associate at Albert Einstein Hospital, Brain Research Institute in São Paulo, Brazil. Patients taking melatonin also had significantly fewer side effects, including daytime sleepiness and weight variation, than patients taking amitriptyline.
A Comparison of Melatonin, Amitriptyline, and Placebo
Dr. Gonçalves and colleagues recruited 178 patients for a trial comparing melatonin, amitriptyline, and placebo. Eligible patients were between ages 18 and 65, met the International Headache Society’s criteria for migraine, and had two to eight attacks per month. Subjects’ mean age was approximately 37, and 133 patients were female. Patients kept headache diaries that included information such as headache intensity, duration, and analgesic use. A migraine headache day was defined as a calendar day with any occurrence of migraine headache pain for at least 30 minutes. A four-week period established baseline information. Subsequently, 59 patients were randomized to receive 25 mg of amitriptyline daily, 60 patients were randomized to receive 3 mg of melatonin daily, and 59 patients were randomized to receive placebo. After randomization, patients were treated for 12 weeks and continued to record their headaches.
The study’s primary outcome was migraine frequency, which was defined as the number of headache days per month. Secondary end points included the number of patients who had a reduction of headache frequency greater than 50%, migraine intensity, migraine duration, and analgesic use.
Melatonin Decreased Headache Days and Migraine Attacks
The number of headache days per month decreased by nearly three for patients taking melatonin. The number of headache days per month decreased by approximately two for patients taking amitriptyline and by one for controls.
Patients taking melatonin had approximately 2.5 fewer migraine attacks, and patients taking amitriptyline had about two fewer migraine attacks. Analgesic use decreased by approximately three units for patients taking melatonin, and by about 2.75 units for patients taking amitriptyline. By comparison, analgesic use decreased by approximately 1.5 units among controls.
About 20 patients taking melatonin reported side effects, compared with more than 30 patients taking amitriptyline. Approximately 11 patients taking melatonin had daytime sleepiness, compared with 23 patients taking amitriptyline. Mean weight variation was –0.14 kg for patients taking melatonin, compared with 0.97 kg for patients taking amitriptyline.
“Melatonin is effective for migraine prevention and very tolerable,” Dr. Gonçalves told Neurology Reviews. “Melatonin could be a cost-effective option, and headache specialists and neurologists now have a scientific basis for recommending melatonin for migraine prevention.” Further research is needed to find the best dose and to understand melatonin’s role in treating migraine comorbid with insomnia, anxiety, and mood disorders, he concluded.
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