Anticonvulsant Use for Prophylaxis of the Pediatric Migraine

Lea S. Eiland, PharmD, BCPS; Teri Woo, PhD(c), MS, RN, CPNP; Elizabeth Farrington, PharmD, FCCP, BCPS

Disclosures

J Pediatr Health Care. 2007;21(6):392-395. 

In This Article

Topiramate

Topiramate is the anticonvulsant for which the most data have been compiled in children. Although not Food & Drug Administration indicated, several trials have evaluated its use in the pediatric population. First, it was studied in an open-label trial of 97 children (mean age approximately 13 years) who presented to a headache clinic and experienced more than three headaches per month (Hershey, Powers, Vockell, LeCates, & Kabbouche, 2002). Children initially were started on topiramate monotherapy or used it as an adjunct agent (58%). The majority of children had migraines or migraines with aura, as defined by the International Headache Society. Prior to therapy the average headache frequency was 16.5 (±10) episodes per month. The mean duration was 8 (±9) hours, and severity was 6 (±1.9) on a 10-point scale. At the first follow-up, 80.6% of patients (n = 75) reported an overall improvement in their migraines. Topiramate doses ranged from 12.5 to 200 mg/day, with an average of 84 (±38.6) mg. Only 12.5% of patients reported no change in their migraines. Patients continued to report overall improvement in migraines at the second (n = 41) and third (n = 17) visit. Specifically, headache frequency decreased to 11.6 (±10.2) at the first visit, 9.4 (±8.4) at the second visit, and 8.7 (±10.8) at the third visit, all statistically significant compared with baseline. The headache duration decreased to 5.7 (±9.8) hours at the first visit. Although not statistically significant, it may be clinically significant for some patients. The second and third visits were statistically significant at 3.7 (±6.2) and 1.9 (±2.2) hours, respectively. Severity decreased to approximately 5 out of 10 for all subsequent visits.

A strength of this trial is that it included evaluations of school days missed and the Pediatric Migraine Disability Assessment (PedMIDAS). School days missed decreased from 2.7 (±7.4) to 1.2 (±2.3), P < .05. The PedMIDAS is a scale that assesses school absences and performance as well as disabilities at home or in the social environment. The PedMIDAS score was reduced by 50% in 48.6% of children at the first visit. At the second visit, 62.5% of children reached this response. Both of these results were statistically significant compared with baseline scores.

Cognitive effects were the most common adverse effect seen with topiramate (12.5% at the first visit); however, only three patients discontinued the medication because of this effect. Paresthesias were seen at the first visit (2.8%), but 7.3% experienced it at the second visit. Patients were asked to drink orange juice to help with this adverse effect. At the first visit, 5.6% of patients had weight loss or appetite changes, but only 2.4% reported these effects at the second visit. However, the weight loss was greater (-2.7 kg ± 5.2, P < .001) at the second visit.

Overall, this study found topiramate to be effective for decreasing migraine frequency, duration, and severity in children, as well as reducing the school days missed and improving quality of life in the child. Limitations included the open label nonblinded design, with a possible placebo effect in the children.

Winner and colleagues (2005) conducted a multicenter, parallel-group, double-blind trial comparing topiramate with placebo in 162 children, aged 6 to 15 years. Patients were randomized in a 2:1 fashion, topiramate to placebo. Patients had to experience 3 to 10 migraine days (with or without aura) for 3 months prior to enrollment and the same during the 4-week prospective baseline phase. Patients for whom two or more migraine prophylaxis therapies had failed or who used other prophylaxis therapy within 14 days of enrollment were excluded from this study. Parents kept headache diaries during the baseline phase and treatment phases. The study consisted of an 8-week titration phase (25 mg/day initially and increased to 200 mg/day maximum) and a 12-week maintenance phase. The average daily dose during the maintenance period was 2 mg/kg/day. The baseline number of migraine days was 5.4 ± 1.8 per month.

In the intention to treat group (n = 157)—patients who had at least one dose of study medication and one post-baseline efficacy measurement—topiramate reduced the mean migraine days per month by 2.6 and placebo reduced it by 2 (P = .61). The per-protocol group (n = 126) showed significance with topiramate versus placebo in reducing the mean headache days by 2.8 and 2.2, respectively (P = .033). However, when examining only the last 28 days of therapy, topiramate reduced mean migraines day by 3.1 versus 2.4 with placebo in the intention to treat group (P = .023).

A total of 54.6% of patients taking topiramate and 46.9% of patients taking a placebo experienced a ≥ 50% reduction of mean migraine days per month. No difference was found between groups. However, 32.4% of patients in the topiramate group experienced ≥75% reduction in migraine days, whereas only 14.3% of patients taking a placebo had the same effect (P = .02).

Common adverse effects included upper respiratory tract infections, anorexia, weight loss (-0.7 kg ± 3.9 change), gastroenteritis, paresthesia, and somnolence. Although the primary endpoint of the study was not significant, outcomes favored topiramate for reducing mean migraine days per month in children.

A 24-patient case series also found topiramate to be beneficial for migraine prophylaxis in children (aged 6-14 years) for whom other prophylaxis medications had failed (Campistol, Campos, Casas, & Herranz, 2005). This open-label evaluation provided topiramate after a 1-month wash-out to patients. Topiramate was titrated up to 200 mg daily or 6 mg/kg/day. The mean monthly migraine episodes decreased from 3.6 at baseline to 2.9 at 2 month (P < .0001) and 2.7 at 4 months (P = .001). Severity decreased while the subjects took topiramate; in addition, 90% of children experienced a shorter migraine than previously. Phonophobia, photophobia, and nausea all produced a statistically significant decrease at months 2 and 4 while the subjects took topiramate. No patients experienced worse headaches while taking topiramate.

Common adverse effects included impaired concentration, emotional instability, paresthesia, anorexia, asthenia, and weight loss. A -1.7 kg ± 0.6 kg changes in weight was seen over the 4-month period, but this finding was not statistically significant.

These three initial studies show positive results for topiramate use in children for migraines. Three other trials evaluated topiramate in older adolescents and adults and found beneficial results as well (Brandes et al 2004, Silberstein et al 2004, Shaygannedjad et al 2006). Topiramate may be considered in pediatric patients who require migraine prophylaxis. Adverse effects, such as impaired concentration and paresthesias, may limit topiramate use in some children.

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