Preventing Pediatric Migraine: What Treatment Is Best?

A Trial of Migraine Prevention in Pediatrics

The Childhood and Adolescent Migraine Prevention (CHAMP) trial[1] sought to improve the quality of the evidence about prevention of migraine among children and adolescents. The two active drugs tested in the study (amitriptyline and topiramate) were chosen on the basis of consensus views that they were the ones most commonly used to prevent migraine in kids. The main hypothesis tested was that both of the active treatments would perform better than placebo, and Powers and colleagues also hypothesized that one of the active treatments would prove superior to the other.

The CHAMP trial enrolled children (aged 8-17 years) at 31 US sites. To be eligible for enrollment, the children must have experienced at least 4 days of headache during a 28-day assessment period (baseline). In addition, the children had at least "mild" disability, on the basis of an established pediatric migraine disability scale.

The children were randomly assigned in a 2:2:1 ratio to receive the two active treatments and the placebo regimen, respectively. All regimens were administered twice each day. Amitriptyline was dosed at 1 mg/kg daily, and topiramate was dosed at 2 mg/kg daily to start. Once the children experienced appropriate dose escalation, they were maintained on a 16-week treatment phase at their highest tolerated dose.

After 24 weeks of treatment, the children completed a 28-day headache diary that served as the post-treatment outcome, compared with headache days at baseline. A treatment success was any child who experienced a 50% or greater decrease in the number of headache days between the baseline and the final assessment. Changes in headache-related disability, and other secondary outcomes, were also assessed.

Of note, the original trial planned to enroll 675 patients, but it was discontinued at the first planned interim analysis because of lack of difference between the treatment groups and the placebo group. A total of 328 patients had data available for the primary outcome. The average age of enrollees was 14.2 years, and 68% were female. The sample was mostly white (70%), but with a notable proportion of black enrollees (19%), and 88% were of non-Hispanic ethnicity. The average number of days of headaches during the baseline period was 11.4.

For the primary outcome, there was little difference among the groups. For example, 52% of the amitriptyline group and 55% of the topiramate group experienced a reduction of at least 50% in number of headache days, but this compared with 61% of the placebo group. The disability score fell by one half on average across all of the treatment groups, yet neither comparison of disability scores in the active treatment groups with the score in the placebo group was significant. Headache days dropped from the average of 11.14 to 4.6-5.2 (depending on group) per 28 days; again, these differences were not statistically significant.

Of note, 5% of the amitriptyline group withdrew owing to side effects, compared with 6% of the topiramate group and 2% of the placebo group. These differences did not reach statistical significance. There was a statistically significant difference in the type of side effects, with fatigue and dry mouth both occurring twice as often in the amitriptyline group than the placebo group. Paresthesias and weight loss were three times more common among the topiramate group than the placebo group.

The authors concluded that there were no significant differences in response among the two treatment groups compared with placebo during 24 weeks of active treatment.


For anyone brave enough to dive into treating adolescent migraine and headache, this trial comes as a severe disappointment. As pediatric providers, we often lament the lack of randomized trial evidence in children, and it is both disappointing and sobering that the two drugs suggested by experts and previous trials to offer the best opportunity for prevention of migraine had so little effect.

On the positive side, the notable placebo effect, regression to the mean over time, or true improvement over time (just three of the potential competing hypotheses to explain the lack of differences) offer some hope for patients and providers. In an accompanying editorial, Jackson[2] commented that the marked placebo response rate in this study is commonly seen in headache trials.

Jackson also offers some good advice for how to respond to these findings. Rather than providers taking the approach that "nothing works," we should focus on working with patients on nonpharmacologic approaches; being a supportive medical source; and considering use of less potentially problematic medications, such as acetaminophen or ibuprofen, as prophylaxis. Of course, the data available for nonpharmacologic approaches to preventing headache are also woefully thin, and long-term use of ibuprofen or acetaminophen poses problems. However, focusing on hope for improvement is an important aspect of treatment and appears to be a reasonable expectation for both patients and providers.

(Source: Medscape Pediatrics - 2017 WebMD, LLC)

1. Powers SW, Coffey CS, Chamberlin LA, et al; CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376:115-124. Abstract
2. Jackson JL. Pediatric migraine headache still searching for effective treatments. N Engl J Med. 2017;376:169-170.