PHILADELPHIA – For the first time, the triptan, zolmitriptan nasal spray has been found to be effective in the short-term treatment of migraines in adolescents, Paul Winner, D.O., reported at the annual meeting of the American Headache Society.
Seven triptans are currently approved for adult migraine treatment, but none of them are approved for use in adolescents, noted Dr. Winner, director of the Palm Beach (Fla.) Headache Center.
He reported on a multicenter, randomized, double-blind, placebo-controlled trial that used a novel design in which 248 adolescents were initially enrolled, and then 171 were selected for the intent-to-treat group based on lack of response to zolmitriptan in a single-blind placebo challenge (see box).
The study was supported by AstraZeneca, the maker of zolmitriptan nasal spray (Zomig). Dr. Winner has served as a researcher, speaker, and consultant to the company.
In the 171 adolescents (mean age 14.1 years), who were treated for a total of 275 migraine attacks, zolmitriptan nasal spray produced significantly higher headache response rates than placebo at 1 hour post dose (58% vs. 43%), with an onset of action as early as 15 minutes.
At 1 hour after treatment, 28% of the adolescents in the zolmitriptan group were pain free, compared with 10% of those in the placebo group.
Also, 51% of those in the zolmitriptan group were able to resume normal activities vs. 38% of those in the placebo group. At 2 hours after treatment, 54% of those in the zolmitriptan group were pain free, vs. 36% of those in the placebo group.
There were no serious adverse events, and no one withdrew from the study because of adverse events.
“We found that the treatment was effective, fast, and well tolerated,” Dr. Winner told this newspaper.
“Hopefully, this will begin the process of getting some of these medications [triptans] approved for adolescents, a group that can clearly benefit from them,” he noted.
Triptans should not be used in all adolescents with migraine, he added, but there is a definite need for such treatment in those who do not respond to over-the-counter medications and have migraine-related disability that prevents them from normal functioning.
Study Excluded Placebo Responders
In previous studies on triptans in adolescents, placebo response rates that were significantly higher than those in adult patients with migraine prevented primary end points from reaching statistical significance, Dr. Winner said.
So he and his associates used a novel design that excluded patients who responded to placebo.
The study initially enrolled 248 adolescents and treated all of their migraine attacks with placebo nasal spray. In this single-blind phase of the study, patients who responded within 15 minutes were excluded, leaving only 171 placebo nonresponders in the intent-to-treat group.
In the double-blind phase, placebo response rates were similar to those in adult studies, Dr. Winner said.
The use of a placebo challenge to screen out placebo responders “needs to be the standard of design moving forward,” he said. “Old designs just don't work.”
The study design yielded an interesting finding, he added: “Once a placebo nonresponder, not always a placebo nonresponder.”
The Food and Drug Administration, which initially approved the placebo challenge design, requested an analysis that included all 248 patients. This analysis assumed that all patients in the placebo-response group (none of whom actually received subsequent treatment) would have responded to placebo and not responded to treatment, had they been included in the double-blind part of the study. In this worst-case scenario, no significant results were obtained.