Abstract
Sumatriptan, a serotonin-1 receptor agonist specially developed for migraine, became available as a licensed product for adults more than 20 years ago. Since then, numerous controlled studies with sumatriptan have been carried out and it is widely used in adults. However, the story has not been as successful in children and adolescents as in adults. Of the few studies performed, most have shown a high placebo response rate (1–4). High placebo response has been found also in other triptan studies in children (1–4). It may be due to several factors, such as study design and shorter duration of migraine attacks in young patients (1–4). Shorter duration means a strong tendency to spontaneous recovery, which is found in placebo-treated acute attacks.
Two controlled clinical studies have been reported to show efficacy against placebo with sumatriptan nasal spray (5,6), which is licensed for the treatment of migraine in children aged 12 years or older in the European Union (EU), Australia and New Zealand, but not in the United States and Canada. Only a few clinical studies have evaluated sumatriptan tablets in children and adolescents. In one of the studies, both the response to sumatriptan and to placebo was low and not statistically different (7). In one study with sumatriptan and naproxen sodium combination tablets, the pain-free response rate to the active combination was statistically significantly higher than to placebo (8). In other sumatriptan studies, the response rates both to sumatriptan and to placebo have been similarly high as in other studies with triptan tablets. Sumatriptan tablets have not yet been licensed for the treatment of migraine in children and adolescents.
A group of Japanese investigators bring their contribution to a small series of pediatric sumatriptan studies (9). They report results of a double blind, placebo-controlled, 17-center, parallel-group study in adolescents, who treated one acute migraine attack either with a 25 mg sumatriptan tablet or with a 50 mg sumatriptan tablet or with placebo. They enrolled 178 patients, of whom 144 patients completed the study and were included in the analysis. As the primary endpoint (i.e. pain relief) was considered at two hours post-dose, the percentage was higher for placebo than for the active drug (38.6% vs 31.1%). The same endpoint at four hours post-dose was reported more often after sumatriptan (63.5%) than after placebo (51.4%), but the difference failed to achieve statistical significance (p = 0.142). The authors conclude that sumatriptan did not show statistically significant pain relief at two hours post-dose as compared to placebo. Both doses of sumatriptan tablets were well tolerated.
The pain relief measures that Japanese investigators chose as primary endpoint were clinically useful, even if the best two-hour primary endpoint according to the International Headache Society (IHS) recommendations is pain freedom (10).
In almost all earlier triptan trials, the lowest response rates have been approximately 49% of the active drug. Japanese response rates to both placebo and sumatriptan are lower. It is hard to say why. But one could speculate that it may be because of the patients selected for the study—either their migraine characteristics or perhaps even their ethnic pharmacogenetic specificity.
Future studies could include also crossover designs (to reduce the number of patients needed and placebo effect (3,10)) with clinically meaningful endpoints (such as complete pain relief, time to onset of relief and time to meaningful relief of symptoms (11)). Clinical efficacy of sumatriptan and other triptans in children and adolescents with migraine still needs to be reported in controlled trials.