Clinical Question: Is topiramate effective in preventing migraine headaches?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: The authors enrolled patients who reported three to 12 migraine headaches during the four weeks preceding enrollment. Patients with multiple failures of traditional prophylactic treatments, those who used triptans or ergot more than eight times per month, or who were taking one of a number of medications—beta blockers, tricyclic anti-depressants, calcium channel blockers, high doses of magnesium or riboflavin, mono-amine oxidase inhibitors, or nonsteroidal anti-inflammatory drugs—were excluded from the study. Eligible patients were taken off their migraine preventive medications.

After the washout period, all patients went for four weeks without medication to allow for baseline assessments of headache frequency, severity, rescue treatment, and so forth. The 487 patients were assigned randomly (allocation method not described) to receive split daily dosages of topiramate—50 mg, 100 mg, or 200 mg—or matching placebo. Topiramate was started at 25 mg daily and titrated over eight weeks to the assigned dosage. The study medications were then maintained for 18 weeks.

The researchers, one of whom was a paid consultant for the manufacturer, evaluated the patients every four weeks. The primary outcome of interest was migraine frequency, and the secondary outcomes included time to see an effect, the proportion of patients achieving at least a 50 percent reduction in headache frequency, and frequency of rescue medication use. All outcomes were assessed via intention to treat.

At baseline, patients in each group averaged approximately 5.5 headaches per month. The placebo group and the 50-mg topiramate group each had approximately one headache less per month (P = not significant), compared with approximately two fewer headaches per month in each of the groups taking higher dosages of topiramate (P < .001). Almost one fourth (22.6 percent) of patients taking placebo experienced a 50 percent reduction in headache frequency compared with 35.9, 54.0, and 52.3 percent taking the ascending topiramate dosages (all P < .05). This translates to a number needed to treat of eight, four, and four, respectively. The lower dosage of topiramate did not reduce rescue medication use compared with placebo; the two higher dosages reduced rescue medication use by two each month. The pooled dropout rates because of side effects were 9 percent for placebo and 13, 15, and 23 percent for each of the topiramate dosages, in order from lowest dosage to highest. This works out to a number needed to treat to harm of 25, 17, and seven, respectively.

Bottom Line: Topiramate, in a dosage of 100 or 200 mg daily, is more effective than placebo in preventing migraine headaches in patients who do not have severe symptoms. This study does not indicate whether this helps patients with the most severe migraines or if topiramate is more effective than the other much less expensive and more extensively studied prophylactic agents such as beta blockers. It also does not help us in managing migraine in the most difficult-to-relieve cases. (Level of Evidence: 1b)