Topiramate for Migraine Prevention<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

Abstract

TN 37203 (jbrandes @nashvilleneuroscience.com).Context Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.Objective To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial. Design, Setting, and PatientsA 26-week, randomized, double-blind, placebocontrolled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.Interventions After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks. Main Outcome MeasuresThe primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with Ն50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed. ResultsOf 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (−2.1, P=.008) and topiramate at 200 mg/d (−2.4, PϽ.001) vs placebo (−1.1). Statistically significant reductions (PϽ.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P=.01), 100 mg/d (49%, PϽ.001), and 200 mg/d (47%, PϽ.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P=.003) and 200-mg/d (PϽ.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P=.01) and 200-mg/d (P=.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea.Conclusion Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the doubleblind phase.

How many migraine patients need prolonged (>1 year) preventive treatment? Experience with topiramate

“…Interestingly, among the group of responders in long-term treatment there was only one patient whose headaches became worse while on topiramate. Adverse events were similar to those seen in previous clinical trials with topiramate [11][12][13]. None of these patients discontinued the drug due to unbearable adverse events in the first two years of treatment.…”

Preventive Pharmacologic Treatments for Episodic Migraine in Adults

“…We analyzed dose-response associations and found that an increase in target topiramate dose from 50 to 100 mg/day but not from 100 to 200 mg/ day resulted in a higher response rate (≥50 % reduction in monthly migraine frequency). [72][73][74] Approved drugs improved other patient-centered outcomes in addition to monthly migraine frequency. Topiramate improved quality of life measured by scores on the Headache Impact Test, 75 Migraine-Specific Questionnaire, 76 and Migraine Disability Assessment.…”

“…78 Divalproex in a larger dose of 1,500 mg/day increased the likelihood of a >50 % improvement in whether migraine attacks impaired usual activities or necessitated symptomatic medication and in reducing migraine attacks with nausea, vomiting, phonophobia, or photophobia. 79 Topiramate 73,74,[80][81][82] and propranolol decreased use of drugs for acute migraine attacks. 83 Among off-label drugs, pooled analyses offered lowstrength evidence that the beta-blocker metoprolol (approved for migraine prevention in Europe) and calcium channel blocker nimodipine were better than placebo in reducing monthly migraine attacks by ≥50 % ( Table 2).…”

Current and prospective pharmacological targets in relation to antimigraine action

“…Also lamotrigine, a sodium channel blocker with antiglutamatergic actions, seemed highly effective in reducing migraine aura and migraine attacks in a controlled open study (Lampl et al 2005). Similarly, the anticonvulsant topiramate is effective in migraine prophylaxis (Brandes et al 2004;Diener et al 2004;Silberstein et al 2004). This effect may be mediated by blockade on voltage-activated Na + and Ca 2+ channels and/or blockade of AMPA and kainate receptors.…”