Objective and Study Design: This double-blind, placebo-controlled trial assessed the efficacy of zolmitriptan versus placebo at early time-points post-dose as an acute treatment for migraine and treatment of headache recurrence.
Patients and Methods: Patients (18 to 65 years) with a ≥1-year history of migraine, age of onset <50 years and an average of 2 to 6 migraine headaches per month were recruited by 45 North American research clinics. 1017 patients were randomised to receive treatment for each of 3 migraine headaches of moderate or severe baseline intensity (labelled A, B and C, and given in a randomised order). Within each headache, patients were randomly allocated to different treatment regimens. Each patient treated each of the 3 headaches (A, B and C) with up to 3 doses, i.e. an initial dose (headache A, zolmitriptan 2.5mg or placebo; headache B, zolmitriptan 5mg or placebo; headache C, zolmitriptan 2.5mg), recurrence prevention 8 hours after initial dose [headache A and B, placebo (to maintain blind); headache C, zolmitriptan 2.5mg or placebo] and a recurrence treatment dose, if required (headache A and B, zolmitriptan 2.5mg or placebo; headache C, zolmitriptan 2.5mg). The 2 primary end-points were headache response rates 45 minutes after the initial dose of zolmitriptan 2.5 or 5mg or placebo, and headache response rates 2 hours after zolmitriptan 2.5mg or placebo for the treatment of recurrent headache, in patients responding at 4 hours to the initial dose.
Results: A total of 734 patients treated all 3 headaches. Headache response following an initial dose of zolmitriptan 2.5 and 5mg was significantly greater than placebo by 45 minutes (p < 0.001, p < 0.01, respectively) and was maintained at 1, 2 and 4 hours. Headache response following zolmitriptan treatment for recurrence was higher than that for placebo, but the difference did not reach statistical significance. A dose taken 8 hours after the initial dose did not appear to provide any benefit in preventing recurrent headache.
Conclusions: Zolmitriptan 2.5 and 5mg provides a rapid onset of action with significant relief of migraine headache by 45 minutes post-dose compared with placebo.