The September, 2016, issue of Headache featured a literature review on the role of melatonin in treating migraine and other primary headache disorders. Amy A. Gelfand, MD and Peter J. Goadsby, MD, PhD reviewed existing studies on the use of melatonin to treat primary headache disorders.
What is a literature review?
A literature review is not a clinical trial. Instead, the researchers examine existing evidence. It consolidates known information about a given topic – an important part of the scientific process. When the entire body of evidence is examined in this way, researchers, doctors, and patients all benefit.
- Researchers gain valuable insight as to where they can best focus future studies
- Doctors gain a better understanding of the scientific support for a given treatment
- Patients are better informed to collaborate with doctors on treatment decisions.
What is melatonin?
Melatonin is a naturally-occurring hormone produced in the pineal gland. It plays an important role in sleep. The timing of its release is regulated by the hypothalamus as part of our circadian rhythms. It affects our ability to fall asleep and stay asleep. When working properly, melatonin rises in the evening and falls in the morning. However, light can alter this process by blocking the production of melatonin, even at night.1,2
Melatonin is available over-the-counter as a dietary supplement. It comes in two forms: immediate and sustained-release. It is inexpensive, readily available, and relatively safe. According to the National Institutes of Health, it is used by over 31 million people in the U.S., making it the fourth most commonly used dietary supplement.3
How melatonin affects migraine and other headache disorders
Melatonin for migraine
In theory, the use of melatonin in the prevention of migraine makes sense. Irregular sleep patterns and lack of sleep are known migraine triggers. Drs. Gelfand and Goadsby also note that melatonin levels are lower on migraine days, lower in those with chronic migraine than those with episodic migraine, and lower in women with migraine with aura during menses. Theory isn’t proof though and clinical trials have produced mixed results.1
- In a 2016 study 3 mg of immediate release melatonin performed better than placebo and similar to 25 mg of amitriptyline. Sixty-five subjects were randomly assigned to receive either 3 mg of melatonin, 25 mg of amitriptyline, or a placebo. After three months of use, melatonin reduced migraine attack frequency by 2.7 migraine days per month while amitriptyline reduced attacks by 2.2 per month. Placebo reduce attacks by 1.2 per month. Melatonin was tolerated better than amitriptyline, too.1
- An earlier study in 2010 tested 2 mg of sustained release melatonin against placebo for eight weeks. Forty-six participants were randomly assigned to receive either 2mg of melatonin or placebo for eight weeks. Melatonin performed no better than the placebo and seven percent of participants receiving melatonin reported daytime tiredness and dizziness1.
- Smaller, open-label studies have reported conflicting results in both adults and children. These studies have also documented daytime sleepiness as a common side effect of melatonin use.1
Unfortunately, the design of each study was so different that more studies are needed to explain how or if melatonin is an effective migraine preventive.
Melatonin for other headache disorders
The use of melatonin to prevent cluster headache has been explored more than any other headache disorder. Several well-designed studies support the use of 9-12 mg nightly to prevent cluster headache. Unfortunately, the evidence supporting melatonin’s use to treat other headache disorders is limited to case studies and theoretical speculation. Recommended doses range from 3 mg for tension-type headache up to 30 mg nightly for hemicrania continua.1
With the exception of migraine and cluster headache, all other headache disorders have only been subject to case studies involving a small number of patients. Only two double-blind, randomized, placebo-control studies involving migraine were cited. Until more dose-controlled, well-designed studies are conducted, the question of correct dosing will be subject to educated guesses and trial and error.1
Dietary supplements are not regulated by the same purity and potency requirements as drugs. Specifying the exact brand or formulation tested will allow future studies to be conducted using the exact same supplement to produce reliable results.
This review also acknowledges that there are several ways in which melatonin may help prevent migraine. In addition to regulating circadian rhythms and improving sleep, melatonin is also an antioxidant with pain relieving and anti-anxiety properties.1,2 Knowing exactly which properties affect migraine will improve our understanding of both melatonin and migraine. For example, if future studies determine that melatonin prevents migraine by regulating sleep, home monitoring of a patient’s sleep-wake cycle could be used to determine if they are a good candidate for melatonin therapy.1
We have a long way to go before all these questions are answered. In the meantime, please talk to your doctor before starting melatonin. It may not require a prescription, but a lot is still unknown about its use as migraine preventive. This review gives us a great picture of the current knowledge and a clear road-map for the future.
1 Gelfand, A, MD; Goadsby, P, MD, PhD. The Role of Melatonin in the Treatment of Primary Headache Disorders. Headache. September 2016;56(8):1257-1266.
2 Melatonin: In depth. National Center for Complementary and Integrative Health. Updated April 4, 2016. Accessed January 9, 2017.
3 1.3% of U.S. Adults (3.1 million) used Melatonin. National Center for Complementary and Integrative Health. Updated August 11, 2016. Accessed January 9, 2017.