Silberstein SD, Neto W, Schmitt J, Jacobs D. MIGR-001 Study Group, Topiramate in migraine prevention: Results of a large controlled trial. Arch Neurol. 2004;61:490-495.
Background: Open-label trials and small controlled studies report topiramate's efficacy in migraine prevention.
Objective: To assess the efficacy and safety of topiramate as a migraine-preventive therapy.
Design: A 26-week, randomized, double-blind, placebo-controlled study.
Setting: Outpatient treatment at 49 US clinical centers. Patients were aged 12 to 65 years, had a 6-month International Headache Society migraine history, and experienced 3 to 12 migraines per month, but had 15 or fewer headache days per month during the 28-day baseline period.
Interventions: Participants were randomized to placebo or topiramate, 50, 100, or 200 mg/day, titrated by 25 mg/week to the assigned dose or as tolerated in 8 weeks; maintenance therapy continued for 18 weeks.
Main Outcome Measures: The primary efficacy assessment was a reduction in mean monthly migraine frequency across the 6-month treatment phase. Secondary end points were responder rate, time to onset of action, mean change in migraine days per month, and mean change in rescue medication days per month.
Results: Four hundred eighty-seven patients were randomized, and 469 composed the intent-to-treat population. The mean ± SD monthly migraine frequency decreased significantly for the 100-mg/day group (from 5.4 ± 2.2 to 3.3 ± 2.9; P < .001) and the 200-mg/day group (from 5.6 ± 2.6 to 3.3 ± 2.9; P < .001) versus the placebo group (from 5.6 ± 2.3 to 4.6 ± 3.0); improvements occurred within the first treatment month. Significantly more topiramate-treated patients (50 mg/day, 35.9% [P= .04]; 100 mg/day, 54.0% [P < .001]; and 200 mg/day, 52.3% [P < .001]) exhibited a 50% or more reduction in monthly migraine frequency than placebo-treated patients (22.6%). Adverse events included paresthesia, fatigue, nausea, anorexia, and taste per version.
Conclusion: Topiramate, 100 or 200 mg/day, was effective as a preventive therapy for patients with migraine.
Comment: This is an important study demonstrating the effectiveness of topiramate as a migraine-preventative treatment. It would useful to know both relative and absolute risk reduction for both doses of topimirate versus placebo. From the data presented here, there seems to be little benefit in using the higher 200-mg dose in terms of efficacy. —David S. Millson
This is the second of the placebo-controlled regulatory studies that have led the FDA to issue an approvable letter on topiramate for migraine prevention. The other, abstracted in the July/August issue of Headache, was Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D; MIGR-002 Study Group. Topiramate for migraine prevention: A randomized controlled trial. JAMA. 2004;25;291:965-73. Both studies confirm the same clinical points: 1. 50 mg of topiramate did not differentiate from placebo. 2. 100 mg did not differentiate in terms of efficacy from 200 mg. 3. Both 100 and 200 mg were superior to placebo and in both studies were at about the 50-50 mark, that is 50% of patients achieved a 50% reduction in migraine frequency. 4. 200 mg was associated with a higher frequency of adverse events than 100 mg.
It is always important clinically, however, to distinguish between population studies and individual patient need. We have many patients doing well on 50 or 75 mg topiramate/day, and some who require in excess of 200 mg/day to maximize efficacy.
Also, it is worth noting the quality of these studies—superbly done, published in full in a timely fashion, allowing all clinicians to become knowledgeable about this medication with respect to headache prevention, as the FDA indication becomes official. The authors are to be congratulated. —Stewart J. Tepper