Lewis D, Winner P, Saper J, Ness S, Polverejan E, Wang S, et al. Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age. Pediatrics 2009;123:924-34.
Question
Among adolescents with a history of migraines, is topiramate (compared with placebo) effective and safe for prophylaxis of migraines?
Design
Randomized, controlled trial.
Setting
Multi-center study, both in the US and outside the US.
Participants
106 adolescents (12–17 years of age) with a ≥6-month history of migraine.
Intervention
16 weeks of daily treatment with topiramate (50 or 100 mg/day) or placebo.
Outcomes
Percent reduction in monthly migraine attacks, with the use of the 48-hour rule, from the prospective baseline period to the last 12 weeks of the double-blind phase. The 48-hour rule defined a single migraine episode as all recurrences of migraine symptoms within 48 hours after onset. Secondary efficacy measures included the reduction from baseline in the monthly migraine day rate and the 50% responder rate, safety, and tolerability.
Main Results
A total of 29 (83%) of 35 subjects treated with topiramate at 50 mg/day, 30 (86%) of 35 subjects treated with topiramate at 100 mg/day, and 26 (79.0%) of 33 placebo-treated subjects completed double-blind treatment. Topiramate at 100 mg/day, but not 50 mg/day, resulted in a statistically significant reduction in the monthly migraine attack rate from baseline versus placebo (median: 72% vs 44%) during the last 12 weeks of double-blind treatment. Topiramate at 100 mg/day, but not 50 mg/day, also resulted in a statistically significant reduction in the monthly migraine day rate from baseline versus placebo. The responder rate favored topiramate at 100 mg/day (83% vs 45% for placebo). Upper respiratory tract infection, paresthesia, and dizziness occurred more commonly in the topiramate groups than in the placebo group.
Conclusions
The 100 mg/day topiramate group demonstrated efficacy in the prevention of migraine in pediatric subjects. Overall, topiramate treatment was safe and well tolerated.
Commentary
Most childhood migraine patients will have only one or two migraine headaches a month. When the frequency is more than weekly, the use of a migraine preventative is considered. Headache doctors feel that the preventatives are successful if they can reduce the frequency of headaches by 50%. Sometimes the severity of the headaches is reduced as well. This study demonstrates that topiramate is an effective migraine preventative in teenagers, and secondly, that low dosages of topiramate are no more effective than placebo, and one needs to find an appropriate dose (100 mg a day) for efficacy. Based on my personal referral-based experience, I think the latter finding is the critical point for our practice. Many patients rarely get to 100 mg a day before coming to see me as a headache specialist. As pediatricians, I do wonder if we have a tendency to inadequately dose pain medications for our patients. There are, however, concerns that the paper did not address. A commonly associated side effect of topiramate is problems with word finding and difficulty concentrating. In the references quoted in the Lewis et al paper, these adverse effects were noted in over 10% of adult patients. Unfortunately this current study adds no insight as to the frequency in which these side effects occur in teens. An additional challenge for the field of headache medicine is to determine which of the preventative medications is best for the teenage or preteen patient. Is topiramate more efficacious than amitriptyline, propranolol, or cyproheptadine? Which medication is the most cost effective? The price of a one month supply of amitriptyline is $5, whereas the brand name version of topiramate (Topamax) is over $200 per month. Fortunately, a generic version of topiramate is recently available, which is much lower in cost.
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