Zolmitriptan oral tablet in migraine treatment: high placebo responses in adolescents

The objective of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy and tolerability of the zolmitriptan conventional tablet at three different doses for the treatment of a single migraine attack in adolescents.

Preliminary data from an open-label study suggested that the zolmitriptan conventional tablet could be effective in the treatment of acute migraine in adolescent patients.

Migraine patients aged 12 to 17 years (n = 850) were randomized to receive zolmitriptan 2.5, 5, or 10 mg, or placebo for treatment of a single migraine attack. Patients recorded migraine headache intensity before and after treatment using a 4-point scale.

There was no statistically significant improvement between zolmitriptan 10 mg (2 x 5 mg tablet) and placebo for the primary efficacy variable, headache response at 2 hours, nor any of the secondary variables tested. Two-hour headache response rates were 54%, 53%, and 57% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 58% for placebo. Two-hour pain-free rates were 25%, 19%, and 23% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 20% for placebo. Zolmitriptan was well tolerated, with a tolerability profile similar to the pattern seen in adults.

The similar efficacy between zolmitriptan and placebo appears to be the result of the high placebo response rate. This is a recognized issue in pediatric migraine studies and there is an ongoing debate on ways to address this problem. Since this study was initiated, there has been some debate on the appropriateness of the 2-hour endpoint for response rates in adolescent studies, given the shorter duration of headache pain in adolescents compared with adults. Furthermore, accurate information regarding the timeliness of treatment and reporting of headache-related information by adolescents is difficult.