Several papers have been published over the past few months on the benefits of topiramate in preventing migraine. We summarise some of the key findings.

Topiramate is effective in preventing chronic migraine

• Topiramate is effective in preventing chronic migraine in adults, according to a randomised, double-blind, placebo-controlled trial. Topiramate use began at 25 mg weekly and gradually increased to a dose of 100 mg/day, allowing dosing flexibility from 50-200 mg/day. Existing migraine prevention treatments were continued throughout the trial. Some 32 patients received topiramate and 27 placebo, with subjects experiencing an average number of 15-16 migraine days per four weeks. The average duration of treatment was 100 days for topiramate users and 92 days for placebo users. Topiramate significantly reduced the average number of monthly migraine days by 3.5, compared with 0.2 for placebo (Study 1)
• Low dose topiramate is effective in preventing migraine, compared with placebo and lamotrigine, says an Indian study. Some 60 patients with more than four migraine attacks per month were randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between. Topiramate was more effective in reducing the frequency of migraine compared to placebo (63% response rate; 30% for placebo) and lamotrigine (63% for topiramate; 46% for lamotrigine) and in reducing the intensity of headache (50% for topiramate versus 10% for placebo and 41% for lamotrigine). (Study 2)
• A third study considered the effects of 100mg/day topiramate, compared with placebo in a randomised, placebo-controlled, parallel-group, multi-centre study consisting of 16 weeks of double-blind treatment. The 306 subjects were divided into two groups, with topiramate users having, on average an 86mg/day dose. Topiramate reduced the number of migraine days compared to placebo (by 6.4 days, vs 4.7) (Study 3).

Topiramate's side effects

• Adverse effects were reported by 75% of subjects in Study 1, compared with 37% of placebo users. The most common side effects were nausea, tingling, dizziness, dyspepsia, fatigue, anorexia and attention disturbance
• Adverse events for topiramate were similar to lamotrigine and placebo at around 7-15% (Study 2)
• Adverse effects occurred in 82.5% and 70.2% of topiramate and placebo users, respectively (Study 3).

_{Study 1: Diener H-C, Bussone G,Van Oene JC et al on behalf of the
TOPMAT-MIG-201(TOP-CHROME) Study Group. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 2007 doi:10.1111/j.1468-2982.2007.01326.x
Study 2: Gupta P; Singh S, Goyal V et al Low-Dose Topiramate Versus Lamotrigine in Migraine
Prophylaxis (The Lotolamp Study). Headache 2007;47:402-412.
Study 3: Silberstein SD, Lipton RB, Dodick DW et al, on behalf of the Topiramate Chronic Migraine Study Group. Efficacy and Safety of Topiramate for the Treatment of Chronic Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial. Headache 2007;47:170-180.}

What the WHA thinks

• All three studies are consistent and confirm that topiramate, at various doses is effective in reducing the frequency and intensity of chronic migraine.
• The risk of adverse events is high and it is notable that Study 2 has a lower incidence of adverse effects compared to the other two studies.