The Placebo Response in Studies of Acute Migraine

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.

Abbreviations: CCT, Controlled clinical trial, ICHD, International Classification of Headache Disorders, ITT, Intent to treat, RCT, Randomized controlled trial, RD, Risk difference