Studies on the treatment of migraine in children and adolescents are rare and difficult to design. In particular, the high placebo response in some trials makes it difficult to prove efficacy of a verum drug. We analysed all available placebo-controlled trials on acute and on prophylactic migraine treatment in children and adolescents with respect to different placebo rates (pain free and pain relief at 2 h; rate of responders with >or= 50% attack frequency decrease). We identified eight crossover and 11 parallel group trials on acute treatment. The placebo response rates were considerably lower in crossover trials than in parallel group trials (19.2% vs. 27.1% for pain free after 2 h and 39.4% vs. 56.9% for pain relief after 2 h). In the 10 prophylactic trials included in this analysis, only a small trend towards a lower placebo rate in crossover trials could be observed. Further significant factors associated with a lower placebo rate in childhood and adolescence trials on the acute treatment of migraine were single-centre (vs. multicentre) trials and small sample size. Age and sex were not associated with the placebo response. Our study suggests that parallel group trials on the acute treatment of migraine in children and adolescents show a very low therapeutic gain due to a high placebo rate. The verum response rates, however, are very similar to those seen in adulthood trials. In conclusion, trial designs on the acute and prophylactic treatment of migraine in children and adolescents should consider the specific findings of this analysis in order to exhibit a higher probability of showing significant differences between placebo and verum drug.