"Topiramate Appears Effective and Safe for Prevention of Chronic Migraine: Presented at EFNS"
By Chris Berrie
GLASGOW, UK -- September 8, 2006 -- The new anticonvulsant topiramate is effective for the treatment of chronic migraine, significantly reducing migraine days, acute medication use, and disability, and is well tolerated, according to an investigator-initiated, multicentre, randomised, double-blind, placebo-controlled, parallel-group study.
The burden to society and clinical classification of headache are both heavy and wide, with migraine representing a major factor, according to coprincipal investigator Peter J. Goadsby, MD, PhD, professor of neurology, Institute of Neurology, London, United Kingdom.
Within a classification of chronic daily headache, which would be defined as 15 or more days per month of headache, chronic migraine again plays its part, Dr. Goadsby said during his presentation here on September 4[th at the 10th Congress of the European Federation of Neurological Societies (EFNS).
Chronic migraine is defined as a headache frequency of 15 or more days per month for 3 or more months, 5 or more attacks of migraine without aura (MWoA), 8 or more days per month with a typical MWoA that respond to triptan/ergot therapy, and attacks not attributed to another disorder, and in particular to medication overuse.
Previous research showed that topiramate has significant benefits over placebo for prevention of migraine, so Dr. Goadsby and colleagues designed a study to investigate the use of this agent for treatment of chronic migraine.
The study's inclusion criteria were chronic MWoA for 12 or more days. Dr. Goadsby stressed that they also permitted medication overuse on entry because, as he said, "The vast majority of people come to see us for treatment for migraine due to medication overuse, so we wanted to try to understand whether medication overuse is a complete barrier to treatment."
Exclusion criteria were migraine started after age 50, Beck Depression Inventory score of 30 or greater, use of migraine prophylaxis in the previous 3 months, prior topiramate use, current use of a carbonic anhydrase inhibitor, and use of another anticonvulsant in the previous 30 days.
The primary endpoint was mean change in migraine frequency from baseline to the final 4 weeks of the trial. This was provided for by a 16-week protocol design that started with a 4-week prospective baseline phase that was followed by a 4-week dose titration. From week 4 to week 12, dose flexibility was permitted, followed by a final 4 weeks of the trial at stable dosing for assessment of the primary endpoint. Topiramate use was then tapered over the next 7 weeks.
Secondary endpoints were 50% responder rates, changes in acute medication use, Migraine Disability Assessment Score (MIDAS), 6-item Head Impact Test (HIT-6), and Migraine-Specific Questionnaire (MSQ) scores, and patient satisfaction. Assessments of tolerability and safety were also carried out.
The 27 patients who were randomised to placebo (mean age, 44 years; male, 26%) and 32 to topiramate (mean age, 48 years; male 25%) had no significant differences in baseline mean number of migraine days (16 days both arms), medication overuse (85% vs 72%, respectively), and Beck score (13 vs 9).
With an overall dose for topiramate of 100 mg/day, the primary endpoint demonstrated significant benefits of topiramate use. The placebo group had a 0.2 increase over baseline in migraine days per month while the topiramate group had a significant 3.5-day decrease over baseline (P < .02). Dr. Goadsby noted that this significant (P < .02) benefit with topiramate was also seen at 4 weeks, and from 12 weeks to the end of the trial.
Change from baseline in the MIDAS score for placebo was -3 and for topiramate use it was -21 (P < .04). Significant improvements were seen in patient satisfaction (good/very good, 8% vs 38%, respectively; P < .05) and the change in acute treatment use (-7.0 vs -3.0; P < .01). No significant differences were seen for the MSQ and HIT-6 scores.
In addition, 0.2 % of placebo patients and 22% of topiramate patients achieved a 50% or greater decrease in headache days (P < .01).
When discussing whether patients with medication overuse responded to topiramate, Dr. Goadsby noted that little change to the full data primary endpoint was seen when patients showing medication overuse were considered (placebo, 0.8-day increase over baseline of headache days vs a 3.5-day decrease for the topiramate group, P < .03).
For tolerability to topiramate, there was an increase in the rate of any adverse events of 37% in the placebo group and 75% with topiramate, most of which was due to increases in paraesthesia (7% vs 59%, respectively), vomiting (4% vs 16%), dizziness (0% vs 13%), and nausea (0% vs 9%). However, overall, topiramate treatment was well tolerated.
Dr. Goadsby concluded that this use of topiramate at 100 mg/day does indeed provide benefit to the chronic migraine sufferer, in terms of reductions in migraine days, acute medication use, and disability according to the MIDAS score.
He also stressed the apparent lack of need for medication withdrawal for treatment efficacy, thus questioning the need for such before treatment with topiramate can be initiated.
This investigator-led trial was supported by Janssen-Cilag EMEA.
[Presentation title: Evaluating the Efficacy, Safety and Tolerability of Topiramate for the Prevention of Chronic Migraine. Abstract SC210]
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