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

Department of Pediatrics, Children's Hospital of the King's Daughters, Eastern Virginia Medical School, 601 Children's Lane, Norfolk, VA 23507-1971, USA.
PEDIATRICS (Impact Factor: 5.47). 04/2009; 123(3):924-34. DOI: 10.1542/peds.2008-0642
Source: PubMed


Currently, no drugs are Food and Drug Administration-approved for migraine prophylaxis in pediatric patients. The objective of this study was to evaluate the efficacy and safety of topiramate for migraine prevention in adolescents.
Adolescents (12-17 years of age) with a >/=6-month history of migraine were assigned randomly to receive 16 weeks of daily treatment with topiramate (50 or 100 mg/day) or placebo. The primary efficacy measure was the 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. Several secondary efficacy measures were evaluated, including the reduction from baseline in the monthly migraine day rate and the 50% responder rate. Safety and tolerability were also assessed.
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: 72.2% vs 44.4%) 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.
The 100 mg/day topiramate group demonstrated efficacy in the prevention of migraine in pediatric subjects. Overall, topiramate treatment was safe and well tolerated.

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Available from: Jeffrey S Nye, Dec 22, 2013
    • "The mean dose of topiramate used in several studies varied from 1.7 ± 1 mg/kg/day S.D. to 3.5 ± 1.7 mg/kg/day.[5920] However, Winner et al.[20] suggested that possibly topiramate at dose of 50 mg/day, administered prophylactically, may reduce migraines in adolescents but Lewis et al.[21] evaluated the efficacy and safety of topiramate for migraine prevention in pediatric subjects aged 12-17 years. They found that 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, 72.2% vs. 44.4%). "
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    ABSTRACT: Migraine is a common neurological disorder in childhood and adolescence. Topiramate is a new anticonvulsant drug, recently being used in migraine prophylaxis in adults, although it is not approved by the Food and Drug Administration for prevention of pediatric migraine. The present study was planned and performed to evaluate the efficacy of low-dose topiramate in pediatric migraine prophylaxis. A prospective study, including 60 patients with migraine headaches was performed for a period of two months. The patients were randomly divided into two treatment groups - treated by topiramate < 2 mg/kg/day and > 2 mg/kg/day. All the patients were evaluated at 0, 4, and 8 weeks of the study for the clinical response. The patients receiving topiramate < 2 mg/kg/day (mean dose of 1.2 ± 0.7 mg/kg/day) showed a reduction in the mean (±SD) of migraine frequency from 6.2 (±2.4) to 3.0 (±1.8) episodes per month, headache intensity from 7.2 (±1.95) to 3.7 (±1.8) based on the Visual Analog Scale, and headache duration from 5.4 (±2.1) to 2.2 (±1.3) h. In the patients treated with topiramate > 2 mg/kg/day (mean dose of 2.4 ± 0.5 mg/kg/day), the mean (±SD) of monthly headache frequency reduced from 6.9 (±2.1) to 3.24 (±1.2) per month, intensity from 7.11 (±1.4) to 3.14 (±2.41), and headache duration from 5.2 (±2.4) to 1.8 (±1.2) h, at the end of follow-up (P > 0.05). The most common side effects of topiramate were paresthesias (five patients), anorexia (four patients), drowsiness (four patients). The results of this study demonstrated that low-dose of topiramate (<2 mg/kg/day) is effective, well-tolerated, safe, and suggested as an alternative prophylactic treatment for pediatric migraine.
    No preview · Article · Sep 2012 · Journal of Pediatric Neurosciences
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    • "Topiramate has proven to be an effective and safe treatment for migraine prophylaxis in pediatric subjects aged 12–17 years in a randomized, double-blind, placebo-controlled study [9], although more evidence is required to better establish the efficacy of anticonvulsant agents in the prevention of migraine in children and adolescents [10]. The topiramate pharmacodynamic mechanisms include inhibitory effects on voltage-gated Na+ and Ca2+ channels and on glutamate-activated ion channels as well as variable modulatory effects on γ-aminobutyric acid-activated ion channels at AMPA glutamate receptors [11]. "
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    ABSTRACT: Acute confusional migraine (ACM) is recognized as a rare, but highly disabling migraine equivalent, mostly reported in children and adolescents. Herein we describe the case of a 12-year-old girl admitted to hospital for an acute confusional state and severe psychomotor agitation, associated with a pulsating headache and nausea, which turned out to be a manifestation of ACM. The girl was discharged on topiramate prophylaxis, titrated up to 75 mg/die; no recurrence of confusional and/or headache episodes has been reported over the last 14 months to date. Due to the rarity of this clinical entity, only anecdotal reports about acute and prophylactic treatment of ACM are available in the literature. The case reported herein suggests that topiramate seems to be effective in ACM prophylaxis, although a longer observation period in our patient and more cases are needed to confirm any long-term clinical benefit.
    Full-text · Article · Sep 2012 · Case Reports in Neurology
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    • "In the Journal of Headache and Pain, only one RCT was found (an RCT on deep brain stimulation in 11 patients with chronic cluster headache [31]). In the other (non-headache) journals, I found 16 abstracts of RCTs on headache and migraine [32–47]. "
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    ABSTRACT: A CONSORT statement on the content of abstracts of randomised, controlled trials (RCTs) was published in 2008. I therefore reviewed the abstracts from 2009 to 2010 published on RCTs in Cephalalgia, Headache and other (non-headache) journals. The following items were reviewed: number of patients, reporting of response either in percentages or absolute values, the use of p values, and effect size with its precision. The latter was recommended in the CONSORT statement. A total of 46 abstracts were reviewed and effect size with 95% confidence intervals was only reported in seven abstracts. The influence of the CONSORT statement on reporting in abstracts has so far only had a limited influence on the headache literature.
    Preview · Article · Jun 2011 · The Journal of Headache and Pain
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