Topiramate for Migraine

Abstract & Commentary

Dara G. Jamieson, MD, Associate Professor, Clinical Neurology, Weill Medical College of Cornell University. Dr. Jamieson reports no consultant, stockholder, speaker's bureau, research, or other relationship related to this field of study.

Synopsis: Topiramate at a maintenance dose decreased the mean number of monthly headache days in children with frequent migraines. Tolerability of the medication in children was generally similar to placebo.

Source: Winner PDO et al. Topiramate for Migraine Prevention in Children: A Randomized, Double-Blind, Placebo-Controlled Trial. Headache. 2005;1304-1312.

Headache is a common complaint in children, with the prevalence of actual migraine estimated at 4-11% in children aged 7 to15 years. The disability associated with frequent migraine headaches, including loss of time from school and social activities, has a significant impact on the children and their families. Few medications show efficacy in the acute treatment of migraine headaches in children, since a high placebo response is often seen in clinical trials. No medication is approved for the prevention of migraine headaches in children, although a limited number of medications are approved for migraine prevention in adults. For children with frequent, disabling migraines, a preventative medication which is effective and well tolerated could alleviate the disability associated with chronic headaches.

A publication by Winner and colleagues, a study sponsored by Ortho-McNeil Pharmaceutical, addresses the efficacy and safety in a pediatric population of topiramate, a medication approved for migraine prevention in adults. Children between the ages of 6 and 15 years, with International Headache Society classified migraine with or without aura, were randomized in a double blind study to receive topiramate titrated from 15 mg/day to 2-3 mg/kg/day (n = 112) or placebo (n = 50). The mean average daily dose of topiramate during the maintenance phase was 2.0mg/kg per day. Mean treatment times were 130 days (on topiramate) and 135 days (on placebo). There was no significant difference in discontinuation rate (20.5 on topiramate and 16.0% on placebo); although, more children discontinued because of limiting adverse events on topiramate and because of lack of efficacy on placebo.

The primary efficacy analysis (the reduction in number of migraine days per month during the treatment phase as compared to the prospective baseline phase) did not reach statistical significance (P = 0.061) in the intent-to-treat group. However, a statistically significant reduction (P = 0.033) was seen in the topiramate treated children in the per-protocol population.

Topiramate significantly reduced the mean number of monthly migraine days during the last 28 days of treatment, as compared to placebo. There was a significant decrease in the percentage of children with 75% reduction in monthly migraine days, but there was no significant decrease in children with a 50% reduction in monthly migraine days. Upper respiratory tract infections, anorexia, weight decrease, gastroenteritis, paresthesias, and somnolence were seen more frequently in the topiramate treated children.

Winner et al noted that this study is the first randomized, placebo-controlled trial of an antiepileptic drug for pediatric migraine prevention. The variable statistical significance of the end points may reflect the variability in medication response and tolerance in children. The addition of the tapering phase to the maintenance phase in assessing time of treatment may have underestimated the effect of topiramate. This is supported by the significant efficacy of topiramate compared to placebo during the last month of treatment.

Side effects in children on topiramate need to be closely monitored, with particular concern about cognitive difficulties. Lack of weight gain may be beneficial for some adolescents. While these preliminary results are intriguing, more pediatric studies need to be done on topiramate and other preventative medications in order to provide relief to children with intractable migraines.