Elsevier

The Journal of Pediatrics

Volume 152, Issue 4, April 2008, Pages 527-533.e1
The Journal of Pediatrics

Original article
The Placebo Response in Studies of Acute Migraine

https://doi.org/10.1016/j.jpeds.2007.09.024Get rights and content

Objectives

To characterize the magnitude of the placebo response in trials of migraine therapy in children and adolescents, and to identify its determinants.

Study design

MEDLINE and CENTRAL were searched through November 2006 for randomized controlled trials or controlled clinical trials of pediatric acute migraine pharmacologic treatment that included a placebo comparator group. The main outcomes were headache relief and pain-free response, and effect estimates for risk differences were calculated whenever possible. The influence of placebo response determinants was studied using subgroup analysis. A total of 13 trials (1324 participants in the placebo groups) were included in the analysis.

Results

The pooled placebo responses for pain relief and pain-free at 2 hours were 46% (range, 38% to 53%) and 21% (range, 17% to 26%). Parallel studies conducted in North American centers demonstrated a significantly higher placebo response, as did trials that used 4-point pain scales. Other placebo determinants did not influence the effect estimate, although insufficient data were available to study some of them.

Conclusions

There is a widely variable placebo response in pediatric migraine trials, supporting the continued use of placebo groups and suggesting the need for more research into the placebo effect in the pediatric population.

Section snippets

Methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library, Issue 4, 2006) using the terms “headache,” “migraine,” “cephalgia,” “cephalalgia,” “p(a)ediatric,” “infan,*” “child*,” “teenage,*” and “adolescent*.” We also searched MEDLINE from 1966 through November 2006 using these same terms, along with the search strategy for identifying randomized controlled trials (RCTs) described by Dickersin et al.19 Additional strategies for identifying trials included hand

Results

A total of 5416 potential relevant articles were identified after the first search, aimed at sensitivity. Most were discarded after title or abstract analysis because they were not acute migraine treatment RCTs or CCTs, they did not include children or adolescent groups, or they did not include a placebo comparator group. Only 16 trials remained, of which a further 3 trials were excluded, 2 because the abstracts did not report adequate placebo group data22, 23 and the third because it was an

Discussion

Our systematic review has demonstrated a high and variable placebo response rate in pediatric migraine trials. There are only a limited number of studies in this age group as opposed to adults, in whom more than 100 trials with available placebo data have been reported.16 Although there are few variations in design, quality scores, and migraine definition among these studies, some criteria used for inclusion and the reporting of participant characteristics and outcomes vary sufficiently to make

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