UCSF Pediatric Focus

Could a Simple Supplement Prevent Migraines in Millions of U.S. Kids?

UCSF researcher and pediatric headache expert Amy Gelfand, MD, is leading a study to test whether melatonin can dramatically reduce the number of migraines from which more than 6 million U.S. children and adolescents suffer.

The trial builds on melatonin’s proven efficacy in adults, a pilot trial with teens and frustration with the sporadic effectiveness of the most commonly prescribed migraine medications. Gelfand expects that melatonin – an over-the-counter supplement – can be a safe, inexpensive and well-tolerated alternative.

Why Melatonin?

Some pediatric headache experts have been using melatonin for migraine prevention in select patients when lifestyle modifications, nonsteroidal anti-inflammatory drugs (NSAIDs) and cognitive behavioral therapy have not achieved results. Yet those decisions are based on clinical experience and a few small, uncontrolled studies – not on conclusive research.

Then, in 2016, three papers argued convincingly for a more powerful study on melatonin’s use in the children and adolescents with whom Gelfand works.

One, in the Journal of Neurology, Neurosurgery and Psychiatry, found that in adults, a 3-mg dose of melatonin is better than placebo, more tolerable than the commonly prescribed medication amitriptyline and as effective as amitriptyline in preventing migraines.

A study published in the New England Journal of Medicine found: “There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with the most commonly prescribed medications – amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events.”

Finally, Gelfand co-authored a review article for the American Headache Society, which found: “Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine.”

“The appeal of melatonin is that it appears to have as good a side effect profile as placebo and that it’s a pretty effective natural medication. We believe it’s possible that it works through improving sleep and, possibly, by helping to regulate the hypothalamus, the area of the brain involved in the first part of migraine attacks,” says Gelfand.

Home-Based Study Most Practical

Gelfand recently tested the feasibility of a home-based study, because it can be burdensome for families to get back and forth from a study center. In her pilot trial, 31 participants came to UCSF once to confirm their diagnosis, undergo a neurological exam and learn how to participate in the study from home. Participation included:

  • Wearing a Fitbit to record sleep data, which was transmitted remotely into the study’s database.
  • Responding to a nightly text, which linked participants to a daily headache diary.
  • Speaking by phone every two weeks with a clinician, who encouraged continued participation, answered questions and recorded any side effects.

At the end of the study, participants shipped their medications back, so researchers could do a pill count and check the electronic tracking on the caps. The study proved the feasibility of a home-based approach and, while it was too small to draw conclusions, also found that those taking the melatonin had reduced headache days.

The UCSF Weill Institute for Neurosciences is funding the current study, and UCLA will participate as a second site, with the plan to enroll more than 200 participants over the next two years.