- Michael J. Arnold, MD
Since getting a migraine headache every Friday during junior high school, I have always been interested in preventing migraines. In medical school, I realized that it was likely the nitrates in the hot dogs served on Fridays at the school cafeteria that were to blame – perhaps with a boost from adolescent hormones.
Powerful Placebo Effect
A recent study on migraine prevention in children opened my eyes to the power of the placebo effect. A 2017 National Institutes of Health-sponsored trial comparing topiramate (the only FDA approved drug for migraine prophylaxis in children) and amitriptyline was stopped early because placebo was more effective than either active drug. Although both medications were effective, placebo was even better, producing a 50% reduction in headache frequency in 61% of children assigned to that arm of the study.
In adult studies, the placebo effect is nearly as strong. Between 20 and 50% of patients achieve a 50% reduction in headache frequency with placebo, and few medications do much better. While a portion of this is likely due to the waxing course of migraine, the placebo response rate tends to be over 20% even for patients with more than 15 migraines per month. The best medications, including topiramate, valproate, and some beta blockers, help 25% more people than placebo halve their migraine frequency, leading to a Number Needed to Treat (NNT) of four. Amitriptyline works 9% better than placebo, with a NNT of 12.
Complementary Therapy
If matching placebo gives at least a 25% response rate, could it be worth trying a safe herbal medication with some evidence of being better? Herbal medications such as feverfew, 6.25 mg three times daily, riboflavin 400 mg daily and magnesium 600 mg daily have limited evidence of being better than placebo with only mild side effects. Another small trial suggested that nightly melatonin was better at reducing migraines than amitriptyline and placebo, with the only common side effect being fatigue. Acupuncture has a NNT of 10 for halving the number of migraines when compared to sham acupuncture, but only 4 when compared to usual care.
A complementary therapy to avoid is butterbur (petasites), which has the best evidence for benefit but can be hepatotoxic. Without FDA regulation of the supplement industry, use is not recommended in the United States.
New Injections for Migraine Prevention
You may have heard of erenumab, a monthly injected medication for migraine prevention comprised of antibodies focused on the calcium gene related peptide system. Erenumab is joined by similar medications fremanezumab and galcanezumab, all of which are priced at $575 per monthly injection, compared to the $150 retail price for 60 tabs of topiramate at 50 mg. These injections have evidence of benefit over placebo with NNTs of either 5 or 6 to reduce headache frequency by 50%.
The American Headache Association recommends trying at least two other medication classes before prescribing these injections, but most studies of these drugs specifically excluded patients who had failed multiple previous medications. A single trial did study erenumab in patients who had failed two medications, and the 50% headache frequency reduction was met in 14% with placebo and 30% with erenumab, leading to a NNT of 7.
Short term side effects were rare and minor (injection site reactions and constipation). However, none of these trials followed patients for longer than three months. These medicines may be valuable for selected patients, but much is yet to be proven. An article in the January 1, 2019 issue of AFP covers migraine prophylaxis in more depth.
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Dr. Arnold is AFP's 2019-20 Jay Siwek Medical Editing Fellow. The views expressed in this blog post are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Uniformed Services University of the Health Sciences, Department of Defense, or the U.S. Government.
