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Can Melatonin Prevent Migraines?

Melatonin is a natural medicine with a favourable side effect profile that may prevent migraines.  A recent study compares the effectiveness and safety of melatonin to the commonly prescribed preventive medication amitriptyline.

Migraine headaches are a common condition characterized by recurring moderate to severe headache attacks, autonomic nervous system dysfunction (i.e. vomiting) and in some patients neurological symptoms (i.e. visual disturbances). Drugs to prevent migraines include beta-blockers and other blood pressure medications, tricyclic antidepressants, serotonin receptor antagonists, valproic acid, topiramate, and gabapentin. Despite the array of medications that can be used to prevent migraines, only three to five percent of patients receive preventative therapy. The most common reason for avoiding these drugs is their unfavourable side effect profile.

Since migraine sufferers are required to take a daily dose of preventative therapy in order to prevent migraines, the side effect profile of the medicine is a very important factor to consider. Effective and tolerable options are necessary.

Researchers at the Albert Einstein Hospital’s Department of Neurology in Sao Paulo, Brazil aimed to compare a natural medicine, melatonin, to a commonly used preventative therapy, amitriptyline. Patients were randomized to the melatonin, amitriptyline, or placebo group and followed for 12 weeks. The primary endpoint was the number of migraine headache days per month. As secondary outcomes, the researchers studied the reduction in the severity of headaches, the duration of headache attacks, the number of pain relievers consumed, and the percent of patients with a greater than 50% reduction in migraine headache days.

The results of this study were highlighted in a report on headache from the Canadian Pharmacists Association. The efficacy of melatonin 3 mg and amitriptyline 25 mg were equally superior to placebo for decreasing the number of migraine headache days per month. An important efficacy measure for preventative migraine therapy is a reduction of at least 50% in headache frequency. For this measure, melatonin was superior to amitriptyline. More studies are required to confirm these results and to study other melatonin dosages (5mg, 10 mg) and formulations (i.e. fast dissolving, spray).

The participants did not report any serious side effects throughout the 12-week study. The most common side effect reported with melatonin and amitriptyline was drowsiness. These medications are normally taken at bedtime, but morning sleepiness is still a common side effect. More sleepiness was reported in the amitriptyline group. Since migraine sufferers will likely require long-term preventative therapy, more studies are required to confirm the safety and efficacy over a longer period of time (i.e. at least one year).

Melatonin is a safe, natural medicine that can be used to prevent migraines. It is readily available without a prescription and an inexpensive therapy that has potential to improve the quality of life of migraine sufferers.

Written by Jessica Caporuscio, PharmD


(1) Worthington, I. Headache. Canadian Pharmacists Association RXTX. 2017.
(2) Secondary Reference: Gonçalves AL, Martini Ferreira A, Ribeiro RT et al. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry. 2016.



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