More threads by Retired


OTC Supplement May Aid in Migraine Prevention
Medscape Psychiatry and Mental Health News
Medscape Medical News from the American Academy of Neurology (AAN) 65th Annual Meeting
Mar 26, 2013

San Diego, California — Melatonin, which is widely available in North America as an over-the-counter supplement, is more effective than placebo for migraine prevention and has a more favorable adverse effect profile than the tricyclic antidepressant amitriptyline, new research shows.

Results from a multicenter, randomized, double-blind, placebo-controlled trial showed that 3 mg of melatonin was more effective than placebo and had efficacy similar to that of 25 mg of amitriptyline. Furthermore, it was better tolerated than amitriptyline, with lower rates of daytime sleepiness and no weight gain.

"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 S?o Paulo Headache Center, professor of neurology at ABC Medical School, and senior research associate at the Albert Einstein Brain Research Institute, Brazil.

Link to Headache, Sleep Disorders
Produced by the pineal gland, melatonin is a hormone that helps regulate the sleep/wake cycle. It has been available as a supplement in the United States since the 1990s and is often used to aid sleep and attenuate jet lag.

According to Dr. Peres, melatonin's role in regulating circadian rhythm has been linked to cluster headache, hypnic headache, and migraine.

Further, he 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.

He also noted that there is a bidirectional relationship in which headache can disrupt sleep and lead to insomnia and excessive daytime sleepiness.

Finally, he 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. It also used a slow-release, 2-mg formulation of melatonin, and, although the response rate in the melatonin group was 44%, the placebo group had an exceptionally high response rate of 40%.

Surprise Weight-Loss Finding
To test the efficacy and tolerability of melatonin and amitriptyline vs placebo for migraine prevention, the investigators recruited 178 men and women who met International Headache Society diagnostic criteria for migraine with and without aura and who had 2 to 8 migraine attacks per month.

All patients underwent a 4-week baseline phase during which each participant kept a diary of migraine frequency.

Participants were then randomly assigned to receive 3 mg melatonin (n = 60), 25 mg amitriptyline (n = 59), or placebo (n = 59) for 3 months. Medication was taken between 10 and 11 pm daily.

The study's primary outcome was a reduction in the number of headache days per month. Secondary endpoints included migraine intensity and duration and analgesic use. Tolerability was also measured in all 3 study groups.

The mean reduction in headache frequency was 2.7 in the melatonin group, 2.18 in the amitriptyline group, and 1.18 in the placebo group.

Although migraine frequency did not differ between the 2 active treatment groups, the proportion of responders was greatest in the melatonin group: 54% vs 39.1% for amitriptyline and 20.4% for placebo.

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.

Worth a Try?
Commenting on the study for Medscape Medical News, Tobias Kurth, MD, director of research Institut national de la sant? et de la recherche m?dicale (INSERM), University of Bordeaux, Talence, France, and associate epidemiologist, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, said the researchers "very convincingly" showed that melatonin was as effective as amitriptyline and both were superior to placebo.

"If this is true, this is great," said Dr. Kurth.

Although the study's findings are preliminary and need to be replicated, Dr. Kurth said that given its favorable adverse effect profile, melatonin may be worth a try.

"I'm not aware of any major side effects associated with melatonin. As long clinicians instruct patients appropriately and emphasize the importance of taking the recommended dose at the same time every day it may be worthwhile," he said.

Dr. Peres and Dr. Kurth have disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 65th Annual Meeting. Abstract S40.005. Presented March 20, 2012.


3 mg of melatonin........Timing of administration and formulation is also important. Ideally, 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.

As I meet the diagnostic criteria used for the study, I'd like to try the melatonin regimen in the hopes of reducing the number of migraine episodes as well as sparing the need for my prescribed (triptan) medication.

I discovered labeling of melatonin leaves much to be desired, though I did finally locate one that claims to be "fast acting".

Will let you know how it goes.

A credible source of information about melatonin, including dosing (for other uses) can be found here:
MELATONIN: Uses, Side Effects, Interactions and Warnings - WebMD


After a month's use of melatonin 3 mg nightly, I cannot be sure yet on its effect on reducing migraine episodes, because it's too early for any meaningful conclusion, I can say I have been enjoying a quality of sleep I have not had in some time.

I generally have difficulty falling asleep quickly, but when I take melatonin at 10:00 pm, I am usually asleep in about a half hour, compared to one to two hours before starting the supplement.

The quality of sleep seems better, and if I wake up during the night, I find it easier to fall back asleep.

The only other time I experienced such improved sleep patterns was ten years ago when my doctor prescribed Imovane that worked well, until I developed tolerance to it and it ceased being effective for me.

I know some people find melatonin loses effectiveness for them after a while, but for now it appears to be working for me, for improved sleep, at least.


Are you still taking melatonin,

Thanks for asking!

Yes, I'm into the fourth month of taking 3 mg per day. The quality of sleep is certainly the most significant improvement I've experienced, with the ability to fall asleep more quickly than ever before. Interestingly, by falling asleep earlier, I tend to wake up earlier than my usual time, so I use that time to gradually prepare for the next day. Not being a morning person, getting a slow start is just perfect for me!

With regard to reduced migraine episodes, I still can't say for sure, because I haven't kept a log, which I should do to satisfy my curiosity.

I've been sleeping so well, that I forgot the usual precautions I needed to take in what I eat / drink before bedtime..... just recently I made the mistake of eating a bowl of (delightful) Heavenly Hash ice cream during the evening, forgetting how chocolate keeps me awake......and discovered the melatonin was not sufficiently effective to overcome the chocolate so I didn't fall asleep until 2 am that night:lol:

Bottom line: the improved sleep quality has been worth it for me, and I'll continue as long as it keeps on working.



Bottom line: the improved sleep quality has been worth it for me, and I'll continue as long as it keeps on working.

I'm glad you have been sleeping well Steve.

I seriously think I'm going to give it a try. My T suggested Remeron,but I think I would like to give melatonin a try first.

Does it really matter what brand it is,as long as it's fast acting(there's so many different brands!)?Can I start with a very low dose to see how it will affect me?

I thought I read somewhere that it can sometimes make an anxiety disorder worse.Do you know anything about that?

David Baxter PhD

Late Founder
I don't know of any evidence to suggest it would worsen anxiety, LIT.

Steve, what brand have you been using?


The brand is Natrol 3mg Rapid dissolving. I don't know if it's sold in Canada, as I bought it in Walmart in the U.S. this winter.

By rapid dissolving, it means the tablet breaks down with saliva as soon as it is taken orally, so a glass of water is not required...Plus it has the added bonus of strawberry flavor......yum!
Replying is not possible. This forum is only available as an archive.