Placebo More Effective for Kids Than Two Common Migraine Drugs
Little research has been done on migraine prevention for children and adolescents compared research for adults. In June of 2012, researchers at the Children's Hospital Medical Center in Cincinnati, Ohio, began enrolling subjects 8 to 17 years old for the Children and Adolescent Migraine Prevention Study (CHAMP). The study was also titled Amitriptyline and Topiramate in the Prevention of Childhood Migraine.
On ClinicalTrials.gov, the formal description of CHAMP was:
"The purpose of this research study is to test two medicines for migraine prevention in children and adolescents. The investigators want to see if amitriptyline and/or topiramate are better than placebo (sugar pill) in reducing headache frequency in children and adolescents ages 8 to 17 with migraines. At this time, there are no FDA approved medicines approved in the US for the prevention treatment of migraine headaches in children and adolescents."1
CHAMP was intended to run for five years and was funded by a rare grant from the National Institutes of Health (NIH). Interim assessment, however, provided sufficient data to answer the study questions, and CHAMP has been terminated early. Study results were published in the New England Journal of Medicine in their Online First section on October 27, 2016.
- Double-blind, placebo-controlled trial of amitriptyline, topiramate, and placebo.
- Study participants were 8 to 17 years old with diagnosis of migraine.
- Participants were randomly assigned to receive amitriptyline, topiramate, or placebo.
- The primary outcome was 50 percent or higher reduction in the number of days with migraine.
- Secondary outcomes were migraine-related disability, migraine days, and serious adverse events during treatment.
- A total of 328 patients were included in the study:
- 132 patients were in the group receiving amitriptyline.
- 130 patients were in the group receiving topiramate.
- 66 patients were in the group receiving placebo.
- The primary outcome of 50 occurred in:
- 52 percent of the study participants in the amitriptyline group.
- 55 percent of the study participants in the topiramate group.
- 61 percent of the study participants in the placebo group.
- Participants receiving the active medications had higher rates of adverse events than those in the placebo group.
- In the amitriptyline group, three patients had serious adverse events of altered mood.
- In the topiramate group, one patient had the serious adverse event of a suicide attempt.
"There were no significant differences in reduction in headache frequency or headache-related disability in childhood and adolescent migraine with amitriptyline, topiramate, or placebo over a period of 24 weeks. The active drugs were associated with higher rates of adverse events."2
"Given the null outcome in this trial and the adverse events and serious adverse events reported in the amitriptyline and topiramate groups, the data do not show a favorable risk–benefit profile for the use of these therapies in pediatric migraine prevention, at least over the 24-week duration of the trial. Our findings also suggest that the adult model of headache treatment, in which amitriptyline and topiramate have been effective, may not apply to pediatric patients."2
Comments and implications for patients:
Just as researchers have had to learn that women respond differently to medications than men, they must continue to learn that children and adolescents are not "small adults." It has always been disconcerting to me when parents have told me that their young children were prescribed medications that have potentially serious side effects. Because there are so many options for migraine treatment, why prescribe a medication with possibly severe and even permanent side effects for a child who is too young to understand and report those side effects?
This study clearly showed no advantage to prescribing either amitriptyline or topiramate for children and adolescents. Hopefully, the study results and conclusions will come to the attention of doctors who treat migraine in children and adolescents.
More helpful articles:
1 The Children and Adolescent Migraine Prevention Study (CHAMP). www.ClinicalTrials.gov.
2 Powers S, Coffey C, Chamberlin L, et al for the CHAMP Investigators. Trial of Amitriptilyne, Topiramate, and Placebo for Pediatric Migraine. New England Journal of Medicine. Online First. October 27, 2016.
3 Piper, Lucy. Pediatric migraine drug effectiveness trial falls short. medwireNews. October 28, 2016.
4 Saint Louis, Catherine. Two Drugs for Adult Migraines May Not Help Chidren. The New York Times. October 27, 2016.