Elsevier

The Lancet Neurology

Volume 6, Issue 12, December 2007, Pages 1054-1062
The Lancet Neurology

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

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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<0·0001) than in the topiramate group (0·10, −0·36 to 0·56; p=0·5756; mean difference between groups −1·09, −1·75 to −0·43). Patients in the placebo group had a greater number of days on acute medication than did those in the topiramate group (mean difference between groups −0·95, −1·49 to −0·41; p=0·0007). Quality of life, as assessed by the MIDAS questionnaire, fell in the placebo group but remained stable in the topiramate group. Patients were more satisfied with the efficacy of topiramate than with that of placebo, whereas satisfaction with tolerability was similar in both treatment groups.

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.

Introduction

Migraine is a common neurological disorder, with an estimated yearly prevalence of 4·1–5·7% in men and 13·7–17·3% in women.1 Frequent migraine attacks impair quality of life and ability to carry out daily activities, and decrease productivity as a result of days missed from work or school.2, 3 National and international guidelines for migraine therapy recommend prophylactic treatment in several categories of patient, including those who have frequent or severe attacks, those with uncommon or complicated migraine conditions, and those for whom acute medication is unsuitable or overused.1, 4, 5, 6 Most guidelines recommend that treatment is assessed after 3–12 months, although there is no evidence to support this practice,7 and no controlled trial has investigated what happens when effective prophylactic treatment is discontinued. Theoretically, migraine frequency could return to that reported before treatment began, remain at a frequency reported during treatment, or lie somewhere in-between. A rebound phenomenon, with a steep increase in migraine frequency after the end of treatment, is also possible. We therefore investigated how migraine frequency changes after the end of preventive therapy.

Topiramate is licensed for prophylaxis of migraine, and its efficacy has been shown in several placebo-controlled trials of 6 months' duration.8, 9, 10 In this randomised, placebo-controlled study, the Prolonged Migraine Prevention with Topiramate trial (PROMPT), we compared the effects of discontinuation of topiramate therapy after 6 months with continued treatment for a further 6 months. A secondary aim was to assess the efficacy of topiramate beyond 6 months of use in terms of number of migraine days.

Section snippets

Participants

Patients were enrolled from 88 neurology clinics in 21 countries in Europe and the middle east. Patients were eligible for the trial if they were 18–80 years of age and fulfilled International Headache Society criteria for migraine with or without aura.11 All patients had a history of migraine for at least 1 year, with a mean of at least four migraine days per month during the 3 months before trial entry. All patients needed to be able to keep trial records. Patients were excluded if they had

Results

Participants were recruited between December, 2003, and February, 2005, and the last patient completed the study in May, 2006. Figure 1 shows the trial profile. Of the patients who entered the open-label phase, 68% completed the 26-week period. Two patients (one from each treatment group) did not receive trial medication in the double-blind phase and were excluded from the safety and efficacy analyses. After completion of the open-label phase, 45 eligible patients decided not to proceed to the

Discussion

Our results show that patients who discontinued migraine preventive treatment with topiramate had an increase in the number of migraine days compared with patients who continued treatment. However, topiramate treatment had persistent benefit, because the number of migraine days did not return to pre-treatment values. This has previously been suggested in studies with other migraine preventive treatments such as flunarizine or β blockers,16, 17 although a 12-month placebo-controlled study would

References (20)

  • RB Lipton et al.

    Migraine prevalence, disease burden, and the need for preventive therapy

    Neurology

    (2007)
  • C Dahlof et al.

    One-year prevalence of migraine in Sweden: a population-based study in adults

    Cephalalgia

    (2001)
  • RB Lipton et al.

    Prevalence and burden of migraine in the United States: data from the American Migraine Study II

    Headache

    (2001)
  • G Geraud et al.

    French guidelines for the diagnosis and management of migraine in adults and children

    Clin Ther

    (2004)
  • S Evers et al.

    EFNS guideline on the drug treatment of migraine—report of an EFNS task force

    Eur J Neurol

    (2006)
  • TJ Steiner et al.

    Guidelines for all doctors in the diagnosis and management of migraine and tension-type headache

    (2004)
  • NT Mathew et al.

    General and pharmacologic approach to migraine management

  • JL Brandes et al.

    Topiramate for migraine prevention: a randomized controlled trial

    JAMA

    (2004)
  • HC Diener et al.

    Topiramate in migraine prophylaxis—results from a placebo-controlled trial with propranolol as an active control

    J Neurol

    (2004)
  • SD Silberstein et al.

    Topiramate in migraine prevention: results of a large controlled trial

    Arch Neurol

    (2004)
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