Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial

Summary Background Use of preventive therapy for migraine is often recommended for only 6–9 months, but no randomised, placebo-controlled trials have investigated migraine frequency after the end of prophylaxis. We assessed the effects of discontinuation of topiramate after a treatment period of 6 months. Methods 818 patients who have migraines were enrolled from 88 clinics in 21 countries. After a 4–8-week lead-in period, patients received topiramate in a 26-week open-label phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every week; the dose could be adjusted further in the range 50–200 mg/day, but was stable for the final 4 weeks. Patients were randomly assigned to continue this dose or switch to placebo for a 26-week double-blind phase. The primary endpoint was the difference in number of days with migraine during the last 4 weeks of the double-blind phase compared with the last 4 weeks of the open-label phase. Analysis was by intention to treat. This trial is registered with EudraCT, number 2005-000321-29. Findings 559 patients (68·3%) completed the open-label phase; 514 entered the double-blind phase and were assigned to topiramate (n=255) or placebo (n=259). The mean increase in number of migraine days was greater in the placebo group (1·19 days in 4 weeks, 95% CI 0·71 to 1·66; p Interpretation Sustained benefit was reported after discontinuation of topiramate, although number of migraine days did increase. These findings suggest that patients should be treated for 6 months, with the option to continue to 12 months in some patients.