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A Trial of Topiramate for Migraine Prophylaxis



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Am Fam Physician. 2004 Oct 15;70(8):1579-1580.

Migraine headache is a common and disabling disorder. Less than one third of treated patients report consistently effective results from their current pharmacologic regimens, and many patients do not seek treatment. Habitual overuse of acute medications, including triptans, ergots, and analgesics, can lead to chronic daily headache. Prophylaxis may reduce migraine frequency and prevent dosage escalation of acute therapies. Brandes and colleagues investigated whether an anti-epileptic medication, topiramate, would be effective in preventing migraines.

Patients who were 12 to 65 years of age and had three to 12 migraines a month were included in the study. Patients who had failed more than two previous prophylactic medication trials were excluded, as were patients taking beta blockers, antidepressants, anti-epileptic drugs, calcium channel blockers, and other medications that might confound the trial results. After a washout period of 14 days, followed by a 28-day baseline period, eligible patients were randomized to treatment with placebo or topiramate in a dosage of 50 mg per day, 100 mg per day, or 200 mg per day, with dosages titrated upward in 25-mg weekly increments to the target dosage. After an 18-week maintenance period, patients were eligible to continue an open-label extension after a blinded seven-week transition.

Patients kept a headache and rescue medication diary. The primary efficacy measure was a comparison of the reduction in migraine frequency from baseline. Other measures included the proportion of patients responding to treatment; a change in the number of monthly migraine days, severity, and duration; and a change in number of days requiring rescue medication. Of the 483 patients enrolled, 63 in the placebo group completed the trial, as did 59 in the 50-mg topiramate group, 63 in the 100-mg group, and 70 in the 200-mg group, for a total of 255 patients completing the study. The mean monthly migraine frequency in all patients at baseline was 5.5, and the mean monthly number of migraine days was 6.5. In all groups, 15 to 24 percent of patients were taking prophylactic medication in the three months before the prospective baseline phase.

Topiramate therapy was associated with a greater reduction in monthly migraine frequency than was achieved with placebo. When compared with placebo, the difference was statistically significant in patients receiving 100 mg and 200 mg of topiramate, but not in those receiving 50 mg. Among placebo patients, headaches were reduced from 5.6 per month to 4.5; in the 100-mg topiramate group, headaches were reduced from 5.8 to 3.5 per month, and from 5.1 to 3.0 in patients receiving 200 mg of topiramate per day. The difference at these dosages occurred by one month of treatment and remained statistically significant for the duration of the trial.

A significantly larger proportion of patients in all topiramate groups had at least a 50 percent reduction in monthly migraine frequency compared with the placebo group. Topiramate in the higher dosages also was associated with a statistically significant reduction in mean monthly number of migraine days and number of days requiring the use of rescue medication. Adverse events associated with topiramate occurred in 10 percent or more of patients, leading to discontinuation by some participants.

The authors conclude that, compared with placebo, topiramate at dosages of 100 or 200 mg per day significantly reduces migraine frequency and the number of days requiring rescue medications. Because of adverse events, slow upward titration may enhance tolerability. The study results also suggest that, for migraine prophylaxis, topiramate is at least as effective as other preventive agents, including propranolol, amitriptyline, and valproate.

Brandes JL, et al. , for the MIGR-002 Study Group. Topiramate for migraine prevention. A randomized controlled trial. JAMA. February 25, 2004;291:965–73.


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