Abstract
OBJECTIVE. 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.
METHODS. 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.
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: 72.2% 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.
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.
Migraine headaches are common in children but often are underrecognized and misdiagnosed.1 The mean age of onset of migraine is 7.2 years for boys and 10.9 years for girls.2,3 The prevalence of migraine increases steadily through childhood, with migraine occurring in up to 10.6% of children and adolescents between the ages of 5 and 15 years and up to 28% of adolescents between the ages of 15 and 19 years,4–6 and shifts to female predominance during adolescence.1
Migraine often is associated with considerable detriments to pediatric patients’ quality of life.7,8 In addition, an evaluation of a clinical trial database involving 1932 adolescents 11 to 18 years of age with migraine found that most migraine attacks occurred between 6 am and 6 pm, which potentially would impair school functioning.9,10
No drugs have been approved by the US Food and Drug Administration for migraine prophylaxis in pediatric patients, and there is a lack of well-designed, placebo-controlled trials evaluating potential treatments.1,6,11–14 Topiramate is Food and Drug Administration-approved for use in adults for migraine prophylaxis.15 The results of several randomized, double-blind, placebo-controlled, clinical trials demonstrated that topiramate at 100 mg/day was effective, safe, and well tolerated as migraine prophylaxis for adults.16–21 Several of those trials also enrolled adolescents 12 to 17 years of age.16–19 In a randomized, double-blind, placebo-controlled, pilot study, topiramate at 100 mg/day showed a trend toward reduction of migraine days per month, compared with placebo, for pediatric subjects 6 to 15 years of age.22 The objective of this randomized, double-blind, parallel-group, placebo-controlled study was to evaluate the efficacy and safety of 2 dosages of topiramate, 50 mg/day and 100 mg/day, as preventive migraine treatment for adolescents 12 to 17 years of age.
METHODS
Study Design
The study (study CR002245) was conducted in accordance with the Declaration of Helsinki and followed International Headache Society guidelines regarding entry criteria, treatment duration, end point selection, and overall study design.23–25 Each subject and legal representative gave written consent, according to local requirements, after the nature of the study was explained and before any study-related activity was performed. The study was conducted at 31 US and non-US sites between August 10, 2005, and November 11, 2006, after the protocol was approved at each site by an independent ethics committee or institutional review board.
This was a randomized, placebo-controlled, double-blind, parallel-group study that consisted of a pretreatment phase lasting up to 9 weeks, a double-blind phase lasting 16 weeks, and a taper/exit phase lasting up to 6 weeks (Fig 1). The pretreatment phase of the study included a screening period lasting up to 1 week, a 4-week washout of disallowed migraine-preventive medications, and a 4-week prospective baseline period. Subjects who completed the prospective baseline period and continued to meet all entry criteria were assigned randomly (1:1:1) to receive 50 mg/day topiramate, 100 mg/day topiramate, or placebo. During the titration period, treatment with topiramate (or matching placebo) was initiated at 25 mg/day and gradually increased at the investigators’ discretion to a target dose of either 50 mg/day or 100 mg/day, dosed twice daily, or the maximal dose tolerated by the subjects. In the event of tolerability problems, investigators could recommend dose reduction or a pause or halt of further dose titration. The double-blind treatment phase consisted of a 4-week titration period and a 12-week maintenance period. To maintain the double-blinding, all subjects received 2 matching tablets at each dose (4 tablets per day). Each tablet contained either 25 mg of topiramate or placebo, depending on the group to which the subject was assigned. The placebo tablets were identical to the topiramate tablets in appearance (in terms of size, markings, and color). Subjects maintained headache and medication records during the prospective baseline period, the double-blind phase, and the posttreatment phase. Parents were advised to assist their children in filling out the headache and medication records and in checking these documents for accuracy.
Study design. TPM indicates topiramate.
Subjects entered the posttreatment phase at either completion of the double-blind treatment or discontinuation of treatment during the double-blind phase. The posttreatment phase included a 2-week taper of study medication, a 4-week medication-free period, and a follow-up visit. Medication was tapered at a rate of 25 mg of topiramate (or placebo) every 3 days.
With the assumption of a SD of 55% for all 3 treatment groups and a treatment difference of 43% between each topiramate dose and placebo for the primary efficacy end point and with adjustment for multiple comparisons of the 2 topiramate dosage groups against placebo (2-sided α level of .025), 34 subjects in each group were determined to be necessary to detect the treatment difference with a power of 80.8%, using the 2-sided Mann-Whitney test (assuming the actual distribution was normal). The total sample size was determined to be 102 subjects.
Subjects
Key Inclusion and Exclusion Criteria
Eligible subjects were between 12 and 17 years of age (inclusive), with a history of migraine, as defined with the proposed International Headache Society diagnostic criteria for pediatric migraine (Table 1), for ≥6 months.26 Key inclusion and exclusion criteria are presented in Table 2.
Proposed International Headache Society Diagnostic Criteria for Pediatric Migraine
Key Inclusion and Exclusion Criteria
Randomization and Blinding
Subjects were assigned randomly by using permuted blocks and a computer-generated schedule, with stratification according to age (12–14 years and 15–17 years). Central randomization was implemented in this study. The subject number and treatment code were assigned after the caller telephoned an interactive voice response system. Treatment was taken in the form of identical-appearing capsules at the end of the prospective baseline period (day 1).
Concomitant Medications
Throughout the study, acute headache medications, including nonprescription analgesic agents, nonsteroidal antiinflammatory drugs, triptans, ergot derivatives, and dihydroergotamine mesylate, were permitted for symptomatic relief of headache attacks, in accordance with the dosing requirements, but treatment could not exceed 14 treatment days per month. All medication use was documented.
Efficacy Measures
Primary Efficacy End Point
The primary efficacy end point was the percent reduction in the monthly migraine attack rate over the last 12 weeks of the double-blind treatment phase, compared with the prospective baseline period, with the use of the 48-hour rule. The 48-hour rule defined a single migraine episode as all recurrences of migraine symptoms within 48 hours after onset. All headache counts were based on information obtained from the subjects’ headache records. The monthly migraine attack rate was calculated as the migraine attack count multiplied by 28 and divided by the number of days in the period. The percent reduction was calculated as 100 × [B − D]/B, where B is the migraine attack rate during the prospective baseline period and D is the migraine attack rate during the last 12 weeks of the double-blind treatment phase (or the entire double-blind phase, for subjects who participated in the double-blind treatment phase for <12 weeks). With this calculation, a positive value indicated a reduction from baseline.
Secondary Efficacy End Points
Secondary efficacy end points included the following measures: (1) percent reduction in the monthly migraine attack rate from the prospective baseline period to the last 4 weeks of the double-blind phase, with the use of the 48-hour rule (the definition of this end point was the same as that of the primary end point except that the last 4 weeks of the double-blind phase were used instead of the last 12 weeks); (2) percent reduction in the monthly migraine day rate from the prospective baseline period to the last 12 weeks of the double-blind phase (a migraine day was defined as a calendar day during which a subject experienced ≥1 migraine attack, with or without aura, or a calendar day during which a subject experienced aura only but received rescue medication within 30 minutes after aura onset); and (3) responder rate (a responder was a subject with ≥50% reduction in the monthly migraine attack rate, with the use of the 48-hour rule, from the prospective baseline period to the last 12 weeks of the double-blind phase). Other secondary efficacy measures assessed in this study were the percent reductions in the monthly headache day rate, monthly migraine attack rate with the use of the 24-hour rule, and monthly migraine day with rescue medication rate.
Safety Evaluations
Safety assessments included spontaneous reports of adverse events, clinical laboratory tests, assessments of weight, height, and vital signs, physical examinations, and neuropsychological evaluations. The results of neuropsychological evaluations will be the subject of a future publication. Treatment-emergent adverse events were defined as events that were new in onset or aggravated in severity or frequency after the start of treatment. Serious adverse events were defined as events that were fatal or immediately life-threatening, were persistently or significantly disabling, resulted in or prolonged an existing hospitalization, involved a congenital anomaly/birth defect, or necessitated medical or surgical intervention to prevent permanent sequelae.
Statistical Analyses
Efficacy evaluations were based on the subjects’ headache and medication records. The efficacy analysis data set was the intent-to-treat data set, which included all randomly assigned subjects who received ≥1 dose of double-blind medication and provided ≥1 efficacy evaluation. The primary efficacy end point, that is, percent reduction in the monthly migraine attack rate from the prospective baseline period to the last 12 weeks of the double-blind treatment phase, was analyzed by using an analysis of covariance model on ranks that included subjects’ stratified age at random assignment (ie, 12–14 or 15–17 years of age), treatment group, and analysis center as factors and the monthly migraine attack rate during the prospective baseline period as a covariate. The procedure described by Hochberg27 was used to adjust the type I error rate for multiple comparisons of the 2 doses of topiramate versus placebo. For subjects who dropped out before 12 weeks, all of their efficacy analyses until the time of discontinuation were used.
All secondary end points (except the 50% responder rate) were analyzed by using the same analysis of covariance model on ranks as for the primary end point, with the corresponding baseline variable in the model. The Cochran-Mantel-Haenszel pairwise tests between each treatment group and placebo were used to assess the association between treatment and responder rates, controlling for the analysis center effect. The differences in the proportions of responders between the topiramate and placebo treatment groups were estimated, and 95% confidence intervals were also provided. No multiplicity adjustments were applied to the multiple secondary comparisons with placebo. The summaries for safety evaluations (including adverse events, laboratory test results, and vital signs) were based on the safety analysis set, which included all randomly assigned subjects who received ≥1 dose of double-blind study medication.
RESULTS
Demographic and Baseline Headache Characteristics
A total of 141 subjects were enrolled; of those, 106 subjects were assigned randomly to 3 treatment groups (in a 1:1:1 ratio) (Fig 2). Demographic and baseline characteristics of the treatment groups were similar (Table 3). All subjects were required to be 12 to 17 years of age at the time of screening. Three subjects reached 18 years of age between screening and random assignment and were assigned randomly in the study. Table 3 summarizes ages at the time of random assignment.
Subject disposition. aThree subjects withdrew before receiving any study drug and were not included in the intent-to-treat (ITT) population. TPM indicates topiramate.
Demographic and Baseline Characteristics (Intent-to-Treat Population)
Treatment Exposure
More than 90% of subjects in each topiramate treatment group (94% in the 50 mg/day topiramate treatment group and 91% in the 100 mg/day topiramate treatment group) achieved the target daily dose during the double-blind treatment phase. The duration of treatment (mean ± SD) was 99.9 ± 29.7 days, 102.8 ± 29.0 days, and 98.3 ± 27.2 days for the 50 mg/day topiramate, 100 mg/day topiramate, and placebo treatment groups, respectively. The proportions of subjects taking the target dose at the end of the double-blind phase were 63% and 51% for the 50 and 100 mg/day topiramate groups, respectively; this was likely related to a combination of factors, including noncompliance with the treatment regimen, medication errors at the investigation sites, and dose reductions. The daily dose of study medication (mean ± SD) used during the entire double-blind treatment phase (titration and maintenance) was 40.9 ± 10.1 mg/day in the 50 mg/day topiramate treatment group and 73.6 ± 18.7 mg/day in the 100 mg/day topiramate treatment group.
Efficacy Measures
Primary Efficacy Measure
Topiramate treatment at 100 mg/day resulted in a statistically significant reduction from baseline (adjusted P = .016 versus placebo) in the monthly migraine attack rate, compared with placebo, during the last 12 weeks of the double-blind treatment phase (median: 72.2% [range: 0.0%–100%] vs 44.4% [range: −36% to 100%]) (Table 4). The 50 mg/day topiramate treatment group did not differ from the placebo treatment group (median: 44.6% [range: −125% to 100%]; adjusted P = .798 versus placebo). The 100 mg/day topiramate treatment group had consistently greater percent reductions in the monthly migraine attack rate over time than did the 50 mg/day topiramate and placebo treatment groups (Fig 3).
Median percent reductions in the monthly migraine attack rate over time. TPM indicates topiramate; PBO, placebo; Mo, month.
Reduction in Monthly Migraine Attack Rate From Prospective Baseline Period, With 48-Hour Rule (Intent-to-Treat Population)
Secondary Efficacy Measures
The percent reduction in the monthly migraine attack rate during the last 4 weeks of the double-blind treatment phase was greater than that during the last 12 weeks (median: 100% [range: 0.0% to 100%], 65.5% [range: −70% to 100%], and 61.4% [range: −67% to 100%] for 100 mg/day topiramate, 50 mg/day topiramate, and placebo, respectively) (Table 4). These results show that ≥50% of subjects in the 100 mg/day topiramate treatment group were migraine-free in the last 4 weeks of the double-blind phase. Treatment with topiramate at 100 mg/day, but not 50 mg/day, resulted in statistically significant percent reductions from baseline, versus placebo, in the monthly migraine attack rate during the last 4 weeks of the double-blind phase (P = .015) and in the monthly migraine day rate (P = .002 for the last 12 weeks of the double-blind phase; P = .015 for the last 4 weeks of the double-blind phase) (Tables 4 and 5).
Reduction in Monthly Migraine Day Rate From Prospective Baseline Period (Intent-to-Treat Population)
The majority of the secondary analyses supported the primary analysis results. The 100 mg/day topiramate group was statistically superior to the placebo group in the monthly headache day rate and the monthly migraine attack rate (with the 24-hour rule). Statistical significance was not reached for the monthly migraine day with rescue medication rate. For this end point, a prespecified imputation rule was applied for percent reduction, because 13 subjects did not record any migraine days with rescue medication use in the prospective baseline period.
For all efficacy end points, a greater treatment effect was observed in the last 4 weeks, compared with the last 12 weeks, of the double-blind phase. For the monthly migraine day with rescue medication rate, which did not achieve statistical significance in the last 12 weeks, the median reductions in the last 4 weeks were 66.7%, 75%, and 100% for the placebo, 50 mg/day topiramate, and 100 mg/day topiramate treatment groups, respectively.
Responder Rate
There was a statistically significantly higher 50% responder rate for the 100 mg/day topiramate treatment group, compared with the placebo treatment group (P = .002), but not for the 50 mg/day topiramate treatment group (P = .957). The proportions of responders were 45%, 46%, and 83% for the placebo, 50 mg/day topiramate, and 100 mg/day topiramate treatment groups, respectively. Comparisons based on any definition of “responder” (for example, subjects with 50%, 75%, or 100% reduction in the monthly migraine attack rate in the last 12 weeks), rather than only the commonly accepted 50% reduction criterion, showed that the 100 mg/day topiramate treatment group had consistently higher response rates than did the placebo and 50 mg/day topiramate treatment groups, which performed similarly (Fig 4).
Cumulative response rate. TPM indicates topiramate.
Safety and Tolerability
The proportions of subjects with ≥1 treatment-emergent adverse event were 74% for each of the topiramate treatment groups and 48% for the placebo treatment group (Table 6). The most common treatment-emergent adverse events with higher incidence rates in the topiramate treatment groups, compared with the placebo group, included upper respiratory tract infection, paresthesia, and anorexia.
Incidence of Treatment-Emergent Adverse Events During Double-Blind Phase That Occurred for ≥5% of Subjects in Any Treatment Group (Safety Population)
Six subjects experienced treatment-emergent adverse events that led to withdrawal from the study. In the placebo group, 1 patient withdrew because of worsening hypokalemia. In the 50 mg/day topiramate treatment group, 3 subjects discontinued treatment, because of fatigue (1 subject), nervousness (1 subject), and headache/emotional lability/depression (1 subject). In the 100 mg/day topiramate treatment group, 2 subjects withdrew from the study, because of treatment-emergent fatigue (1 subject) and renal calculus (1 subject). In addition, 1 subject in the 100 mg/day topiramate treatment group withdrew because of epistaxis that started 1 day before random assignment (non–treatment-emergent).
No deaths were reported in this study. Four subjects experienced serious adverse events. Of those 4 subjects, 2 subjects were not assigned randomly to treatment; 1 experienced syncope and 1 infection. The other 2 subjects who experienced serious adverse events were in the 100 mg/day topiramate treatment group; 1 experienced back pain and 1 experienced injury, both of which resolved. The 2 serious adverse events that occurred in the 100 mg/day topiramate treatment group did not lead to discontinuation of topiramate treatment and, in the opinion of the investigators, was of uncertain relation to treatment. There were no clinically significant changes in laboratory parameters between the topiramate treatment groups and the placebo group. Evaluations of adverse events of special concern for topiramate (including rash, ocular, renal, and hepatic events, oligohidrosis/hyperthermia, hyperammonemia/encephalopathy, metabolic acidosis, weight loss, depression/suicide, and suicide-related events) did not reveal any unexpected findings; events were either absent, not clinically relevant, considered by the investigators to be unrelated to topiramate treatment, or consistent with the known safety profile of topiramate.
The weight changes (mean ± SD) from baseline to the end of the double-blind phase of the study were 0.8 ± 2.3 kg, −0.1 ± 1.6 kg, and −0.3 ± 3.2 kg for the placebo, 50 mg/day topiramate, and 100 mg/day topiramate treatment groups, respectively. The percent weight changes (mean ± SD) from baseline were 1.7 ± 3.8%, −0.1 ± 3.0%, and −0.6 ± 5.2% for the placebo, 50 mg/day topiramate, and 100 mg/day topiramate treatment groups, respectively. Dose-dependent weight decreases of <10% from baseline were recorded for 22% in the placebo group, 28% in the 50 mg/day topiramate treatment group, and 48% in the 100 mg/day topiramate treatment group. No subjects had a ≥10% decrease in body weight. No subjects in the topiramate treatment groups discontinued treatment because of weight loss.
Slight dose-dependent decreases in BMI were seen across all treatment groups when baseline values were compared with values measured at the end of double-blind treatment. The greatest mean decrease was seen in the 100 mg/day topiramate treatment group. Subjects in the 100 mg/day topiramate treatment group had a BMI (mean ± SD) at baseline of 21.8 ± 4.1 kg/m2 (median: 21.5 kg/m2). At the end of double-blind treatment, subjects in this group experienced a reduction in BMI (mean ± SD) of 0.4 ± 1.0 kg/m2 (median: 0.2 kg/m2).
DISCUSSION
The management of migraine in children and adolescents requires an individually tailored regimen, including biobehavioral interventions, acute pharmacotherapy, and preventive measures. Migraine management generally focuses on the reduction of headache “burden,” which encompasses frequency, duration, and severity, to alleviate overall disability. For patients whose migraine burden is substantial, preventive measures are central. In addition, management aims to reduce reliance on acute pharmacotherapies and to avoid escalation of the use of such medications, to improve quality of life, to improve the ability of patients to manage their condition, and to reduce headache-related distress and psychological symptoms.5,28 These goals, although developed for adults with migraine, are appropriate for the pediatric migraine population.
There are limited data from randomized, placebo-controlled trials regarding the safe effective use in the pediatric population of preventive migraine treatments commonly used for adult patients with migraine.1,6,13,14 Previous information regarding treatment of pediatric migraine has been inconclusive.6 Consequently, there are currently no drugs approved by the Food and Drug Administration for preventive treatment of migraine in the pediatric population, underscoring a profound, unmet, clinical need.
Previous controlled trials for migraine prevention demonstrated the efficacy of topiramate treatment in adults.16–18,20 The results of a previous, randomized, double-blind, placebo-controlled trial of topiramate treatment for migraine prevention in pediatric patients showed a directional trend in favor of topiramate for the primary efficacy outcome measure of mean reduction from baseline in the number of migraine days per month.22
The results of this trial demonstrated that migraine-preventive treatment with 100 mg/day topiramate for subjects 12 to 17 years of age resulted in a statistically significant reduction from baseline in the monthly migraine attack rate during the last 12 weeks of double-blind treatment, compared with placebo. There were nearly twice as many responders in the 100 mg/day topiramate treatment group than in either of the other treatment groups. The efficacy of 100 mg/day topiramate treatment in reducing migraine attacks was also demonstrated when the last 4 weeks of the double-blind phase and the last 12 weeks of the double-blind phase were evaluated by using the 24-hour rule. In addition, 100 mg/day topiramate was associated with statistically significant percent reductions in the monthly migraine and headache day rates, compared with placebo. At least 50% of subjects from the 100 mg/day topiramate treatment group were migraine-free in the last 4 weeks of the double-blind phase.
Overall, topiramate treatment was safe and well tolerated. There were no deaths in the study and few discontinuations attributable to adverse events. Topiramate is typically used for treatment of epilepsy in pediatric patients at doses higher than the 100 mg/day dose recommended for preventive treatment of migraine in adults. Both the qualitative nature and frequency of adverse effects reported for topiramate in this trial were in accordance with expectations for the doses used and in keeping with the results of previous clinical trials evaluating topiramate as preventive migraine treatment for adults16,17,20,21 and trials with pediatric patients with epilepsy. Safety analyses revealed no unexpected findings. The results of this trial demonstrated that 100 mg/day topiramate showed efficacy in the prevention of migraine in pediatric subjects.
Acknowledgments
Dr Lewis received support from the National Institutes of Health (grants 1UO1NSO45911 and 1RO1NSO4329). Editorial support was provided by George Rogan (Phase Five Communications Inc, New York, NY), with funding provided by Ortho-McNeil Janssen Scientific Affairs, LLC.
Footnotes
- Accepted July 21, 2008.
- Address correspondence to Donald Lewis, MD, Department of Pediatrics, Children's Hospital of the King's Daughters, Eastern Virginia Medical School, 601 Children's Lane, Norfolk, VA 23507-1971. E-mail: dlewis{at}chkd.org
Financial Disclosure: Dr Lewis received funds from Abbott Laboratories as a scientific advisor for study design and from Pfizer to attend a scientific advisory meeting in 2004 and received research grants from Abbott Laboratories, Astra Zeneca, Ortho-McNeil and Almirall. Dr Winner received funds from Merck, GlaxoSmithKline, Ortho-McNeil, Pfizer, Allergan, and Astra Zeneca for speaking, advisory board participation, and consultation and received research grants from GlaxoSmithKline, Ortho-McNeil, Pfizer, Allergan, Novartis, Wyeth, Merck, Forest Laboratories, Elan, Minster Pharmaceuticals, MAP Pharmaceuticals, Easai, and ReSearch Pharmaceutical Services. Dr Saper received speaking honoraria from GlaxoSmithKline, Merck, Ortho-McNeil, Neuralieve, Allergan, Medtronic, Pfizer, and Advanced Neuromodulation Systems and received research grants from Pfizer, Endo Pharmaceuticals, GlaxoSmithKline, Neuralieve, ProEthic, Ortho-McNeil, Johnson & Johnson, Merck, Alexa, Allergan, Cypress Pharmaceutical, Advanced Neuromodulation Systems, MAP Pharmacueticals, Medtronic, Torrey Pines Institute for Molecular Studies, and Schwarz Pharma. Drs Ness, Polverejan, Wang, Kurland, Nye, Yuen, Eerdekens, and Ford were employees of Johnson & Johnson.
This trial has been registered at www.clinicaltrials.gov (identifier NCT00210535).
What's Known on This Subject
Migraine occurs in 10.6% of children and adolescents between the ages of 5 and 15 years and 28% of adolescents between the ages of 15 and 19 years. There are few well-designed trials evaluating migraine-preventive treatments for pediatric patients.
What This Study Adds
The results of this trial demonstrated that topiramate at 100 mg/day is safe, effective, and generally well tolerated when used for migraine prevention in patients 12 to 17 years of age.
REFERENCES
- Copyright © 2009 by the American Academy of Pediatrics
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