Melatonin for Migraine Prevention
Reviewer: Tori Hudson, N.D.
Author: Goncalves A, Ferreira A, Ribeiro R, et al.
Reference: Randomized clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. Published online J Neurol Neurosurg Psychiatry May, 2016
Design: This was a randomized, multicenter, parallel-group design in which melatonin was compared with amitriptyline and placebo for 12 weeks. Patients were randomized into one of three groups: placebo, melatonin 3 mg or amitriptyline 25 mg before bed. After a 4 week baseline phase, 196 patients were randomized with 65 in the placebo group, 66 received amitriptyline and 65 received melatonin. Those numbers in each group decreased slightly as 18 were lost to follow-up.
Participants: Patients were ages 18-65 years old and had migraines with or without aura for at least 1 year and first onset prior to age 50 years. They were included if they had at least three migraine headache attacks or four migraine headache days (a headache of at least 30 minutes in duration) per month but < 15 headache attacks per month during each of the previous 3 months prior to the screening visit. Both men and women were included but women had to either be unable to bear children or were not pregnant and using adequate contraception. Patients were excluded if they had a past or present psychiatric disorder, used ergotamine, triptans, opioids or combinations of those for > 10 days per month or just an analgesic for > 15 days/month for > 3 months. They were also excluded if they were unable to discontinue their prophylactic medications, or had previously taken melatonin, amitriptyline or agomelatine or had uncontrolled hypertension at the screening visit or at randomization.
Primary outcome: The primary end point of efficacy was frequency in number of migraine headache days per month.
Key findings: Mean headache frequency reduction was 2.7 migraine headache days in the melatonin group, 2.2 for amitriptyline and 1.1 for placebo. Melatonin was as effective as amitriptyline in the primary end point. Melatonin was superior to amitriptyline in the percentage of patients with a greater than 50% reduction in migraine frequency and melatonin was better tolerated than amitriptyline. Melatonin and amitriptyline were both more effective than placebo in reducing the number of analgesics used, and the duration and intensity of migraine headache attacks.
Practice Implications: Migraines are chronic and debilitating and affect 12-20% of the world’s population. Only about half of patients achieve a 50% reduction in the frequency of their attacks, despite the availability of prophylaxis options. Sadly, only 3-5% of chronic migraine sufferers receive adequate prophylaxis therapy. Multiple mechanisms are involved in migraine headaches, and with individual triggers. I would likely not just rely on melatonin and it’s mechanisms of action but use it along with other known natural agents that can reduce the frequency, duration and severity of migraines.