Melatonin may be more effective than Amitriptyline for Migraine Prevention

Melatonin is an over the counter supplement and it has shown to be more effective than placebo for migraine prevention. In addition, it has a more favorable adverse effect profile than the tricyclic antidepressant amitriptyline.

A study from a multicenter, randomized, double-blind, placebo-controlled trial showed that 3 mg of melatonin was more effective than placebo and had similar efficacy as 25 mg of amitriptyline. In addition, melatonin is better tolerated then amitriptyline without as much daytime sleepiness and no side effects of weight gain.

Melatonin is a hormone that helps to regulate the sleep and wake cycle. It is often used to aid with sleep and help with jet lag. I have used melatonin (3mg or more most nights) to aid with falling asleep when it was suggested by a physician due to trouble falling asleep ever since having a 24/7 headache since 2 days after having 4 wisdom teeth extracted. Difficulty falling asleep has been noted in new daily persistent headache patients (see

A disruption of melatonin has been linked to sleep disorders such as insomnia and delayed sleep phase syndrome which are also linked to headache. Headache is also know to disrupt sleep and lead to insomnia which as been true in my particular case.

In this study researchers found 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 test. Participants were then randomly assigned to receive 3 mg melatonin (n = 60), 25 mg amitriptyline (n = 59), or placebo (n = 59) for 3 months. The treatment was taken sometime between 10 pm and 11 pm each day.

The study found a mean reduction in headache frequency of 2.7 in the melatonin group, 2.18 in the amitriptyline group, and 1.18 in the placebo group.

Melatonin was tolerable and had significantly fewer adverse effects compared with amitriptyline. Daytime sleepiness was the most frequency symptom amongst all three groups but was most pronouced in the amitriptyline group (n = 24). Melatonin was associated with weight loss where 3 patients gained weight with amitriptyline.

It is also important to note that the timing of melatonin is important. It is also better to have a fast-acting rather than a slow-acting release formula according to the one the study’s authors. Many different brands of melatonin can be found at your local pharmacy and some may be more effective than others. I am not sure if enough patients were used in each group in this study for adequate statistical type I and type II errors or if this was tested.

Source: Caroline Cassels, OTC Supplement May Aid in Migraine Prevention, MedScape, March 26, 2013.

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