COMMENTARY

5 Best of 2017: Pediatrics Viewpoints

William T. Basco, Jr., MD

Disclosures

December 28, 2017

In This Article

A Trial of Migraine Prevention in Pediatrics

The Childhood and Adolescent Migraine Prevention (CHAMP) trial[4] tested two active drugs (amitriptyline and topiramate) that are 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 the authors also hypothesized that one of the active treatments would prove superior to the other. The study 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. 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 posttreatment outcome, compared with headache days at baseline. Any child who experienced a 50% or greater decrease in the number of headache days between the baseline and the final assessment was considered a "treatment success."

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 groups, yet neither comparison of disability scores in the active treatment groups with the score in the placebo group was significant. Headache days per month dropped in all groups, but again, these differences were not statistically significant. 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 in the placebo group. Paresthesias and weight loss were three times more common among the topiramate group than the placebo group.

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

Viewpoint

I still contend that the results of this trial come as a severe disappointment. Migraine can be such a vexing problem in general pediatric outpatient practice, where improvement often requires time and the nonpharmacologic interventions that general practices often don't and can't provide may be more helpful than medication. It is disappointing, to say the least, that neither of the drugs that have perhaps the most pediatric data and are felt by many pediatric headache experts to be the "go-to" prevention drugs had so little effect.

Nonetheless, 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, Jeffrey Jackson, MD, MPH[5] commented that the marked placebo response rate in this study is commonly seen in headache trials, so offering pharmaceutical treatment that minimizes side effects, pursuing nonpharmacologic approaches to managing chronic headache, and giving the patient time may still be the best approaches for generalists.

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