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ORIGINAL ARTICLE
Year : 2012  |  Volume : 7  |  Issue : 3  |  Page : 171-174
 

Effective dose of topiramate in pediatric migraine prophylaxis


1 Department of Pediatrics, Booali Sina Hospital, Sari, Iran
2 Pediatric Infectious Disease Subspecialist, Mazandaran University of Medical Sciences, Sari, Iran

Date of Web Publication25-Jan-2013

Correspondence Address:
Mohammad Sadegh Rezai
Pediatric Infectious Disease Subspecialist, Mazandaran University of Medical Sciences, Sari
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1817-1745.106470

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   Abstract 

Objective: 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. Materials and Methods: 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. Results: 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). Conclusion: 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.


Keywords: Pediatric migraine, prophylaxis, topiramate


How to cite this article:
Abbaskhanian A, Sadeghi HR, Erfani A, Rezai MS. Effective dose of topiramate in pediatric migraine prophylaxis. J Pediatr Neurosci 2012;7:171-4

How to cite this URL:
Abbaskhanian A, Sadeghi HR, Erfani A, Rezai MS. Effective dose of topiramate in pediatric migraine prophylaxis. J Pediatr Neurosci [serial online] 2012 [cited 2019 Apr 23];7:171-4. Available from: http://www.pediatricneurosciences.com/text.asp?2012/7/3/171/106470



   Introduction Top


Migraine is a common neurological disorder in childhood and adolescence. It has a prevalence of 5% in children aged 7-10 years and of 17% in adolescents. There is an equal prevalence in girls and boys prior to puberty; however, after puberty, the prevalence is 2-3 times more common in girls. [1],[2] Management of pediatric migraine includes lifestyle changes (in order to avoid foods, habits or environmental factors that may trigger a migraine attack), the use of abortive medications, and preventive measures, which can be either non-pharmacological or pharmacological. [3],[4] Topiramate has been shown to be effective for migraine prevention in adults. Limited data is available for the efficacy and safety of topiramate in the pediatric population. [5] The exact mechanism of topiramate is unknown. [6] It is proposed that epilepsy and migraine share some of the same pathophysiological mechanisms, including abnormal function of voltage-gated sodium and calcium channels, reduced gamma-aminobutyric acid (GABA) -mediated inhibition, and increased glutamate-mediated excitation. [7],[8]

Few uncontrolled studies done to evaluate the efficacy of topiramate in migraine prophylaxis especially in refractory causes confirmed that it could be effective in prophylaxis of migraine headache. [5],[9] Data to support the effectiveness, tolerability, and adequate dosage of pediatric topiramate are not well-reported. The present study was planned and performed to evaluate the efficacy of low-dose topiramate in pediatric migraine prophylaxis.


   Materials and Methods Top


The study was designed as a prospective study and was performed in 60 children (between 5 and 15 years of age) treated with topiramate for prevention of migraine headaches, at a pediatric neurology clinic in north of Iran from March 2011 through September of 2011. The diagnosis of migraine was based on 2005 definition by the International Headache Society which included childhood criteria. [10]

A general evaluation and physical examination were performed in the first visit, and patients were asked baseline laboratory screening tests and a migraine checklist, including demographic and clinical details of the patients such as frequency, duration, and intensity of headache was filed for each person.

Exclusion criteria were as follows:

  1. Prior or current prophylactic treatment for migraine in the last two months
  2. Persistent increasing headache
  3. Change of behavior and school performance
  4. Abnormal neurologic and persistent focal signs (e.g., papilledema)
  5. Neuroimaging studies indicative of a focal neurological lesion
  6. Contraindications for topiramate (e.g., glaucoma, renal stone)
  7. Patients with known case of epilepsy.
After simple randomized dividing the patients into two groups, topiramate was started at a dose of greater or lower than 2 mg/kg/day. For the clinical assessment of the patients, to minimize the potential side effects, the dose was slowly increased 0.5 mg/kg/day in the 2 nd week, divided into two daily doses according to patient's response and tolerance. There were three stages of this study such as at the beginning of study (Base-line), period which was 4-weeks after receiving drugs (phase I) and at the end of 8-weeks after receiving drugs (phase II). Headache severity was scored on a 1-3 point scale with one presenting no effect on daily activity, two for partial inhibition of daily activity and three for loss of daily activities based on the Visual Analog Scale (VAS). The response to topiramate treatment was recorded according to the patients and parents' reports during follow-up visits, and was defined as: Complete cessation of headache attacks (excellent response), reduction of headache frequency more than 50% of baseline (good response), reduction of headache frequency less than 50% of baseline (fair response), No response or increase of headache attacks (poor response). The data analysis were performed by statistical package for social sciences version 13. We analyzed number of headaches per month, changes in Body Mass Index (BMI) and dosage before and after treatment according to the presence or absence of adverse effects, using the Student's t test. The incidence of migraine attacks and adverse effects before and after treatment was analyzed using χ2 nonparametric test. Results are expressed as mean (±SD) and P < 0.05 was considered as statistically significant.

Before starting the study all the patients were given extensive information on the study nature and methods, and we obtained an informed written consent, and patients were advised that they could withdraw from the study at any stage for any reason. This study was performed in accordance with the declaration of Helsinki and subsequent revision and approved by the Ethics committee at Mazandaran University of Medical Science.


   Results Top


Sixty patients who met the inclusion criteria were enrolled in the study. Five of the patients were excluded due to no follow-up, patient's choice or drug intolerance. Ultimately, out of 55 patients who completed the course of study, 30 (54.5%) were girls, and 25 (45.5%) were boys. The mean age was 8 years (range: 6.3-14.5 years). Patients in the two groups were not significantly different regarding age, gender, and other characteristics (P > 0.05). Mean (±SD) numbers of monthly headache frequency at the beginning of the study with topiramate in two groups receiving > 2 mg/kg/day and < 2 mg/kg/day were 6.9 (±2.1) and 6.2 (±2.4), and mean (±SD) duration of each episode of headache at the baseline were 5.2 (±2.4), and 5.4 (±2.1) h, respectively. The mean (±SD) headache intensity at the beginning of the trial was 7.11 (±1.4) and 7.2 (±1.9) and the base line data show that there were no statistically significant differences between the two groups according to base line headache characteristics (P > 0.05). Data about comparison of headache parameters at baseline and after 4 and 8 weeks of treatment are recorded [Table 1]. Frequency intensity and duration of migraine headache decreased significantly between repeated follow-up visits of each patient in the study according to statistical analysis tests [Table 2]. Clinical response was quantified as excellent in 61%, good in 19%, and fair in 13%, with no response in 7% of the patients. Topiramate was well tolerated. No significant reduction in BMI or weight loss occurred during the treatment.
Table 1: Comparison of headache parameters at baseline and after 4 and 8 weeks of beginning the study


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Table 2: Comparison of mean reduction of intensity, frequency, and duration of headache in group after 8 weeks of treatment


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The most common side effects of topiramate were paresthesias (five patients), anorexia (four patients), and drowsiness (four patients).


   Discussion Top


Migraine prevalence estimates vary from 1% to 3% at 7 years and 4% to 11% at 7-15 years. [11],[12],[13] Many children with migraines require prophylactic therapy. [14] The successful treatment of pediatric migraine includes an individually tailored regimen of both non pharmacologic and pharmacologic measures. [15] Non-pharmacologic therapies such as abiding by appropriate sleep patterns, diet, stress reduction and exercise may be helpful in preventing headaches. If the patient can identify triggers, such as particular foods or caffeine, avoidance is recommended, if possible. [14] Many treatments are currently used for migraine prophylaxis, including β-blockers, calcium channel antagonists, serotonin antagonists, antidepressants and anti-epileptics. [16],[17] Topiramate is an antiepileptic drug with established efficacy and safety in older children and adults with epilepsy. [16],[17] Although, before its approval in August 2004. [18],[19] Topiramate has been demonstrated to be helpful in adults, few studies have been conducted to establish evaluating topiramate's efficacy, safety, optimal dose, length of treatment, and side effects in childhood migraine. So this present study was designed and performed to compare different dosage of topiramate in pediatric migraine prophylaxis. In our study, the mean dose in patients receiving topiramate (<2 mg/kg/day) was 1.2 ± 0.7 mg/kg/day. (Range: 0.5-2 mg/kg/day) comparing with 2.4 ± 0.5 mg/kg/day in group receiving more than 2 mg/kg/day. 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. [5],[9],[20] 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%). Campistol et al. [22] presented that effective mean dose of topiramate in pediatric migraine prophylaxis is 3.5 ± 1.7 mg/kg/day. The results of this study show that though both groups had (<2 mg/kg/day vs. >2 mg/kg/day) decreased monthly headache frequency, intensity and duration. Borzy et al. [23] studied a group of 21 children aged 6-18 years who were diagnosed with chronic daily headaches and treated with topiramate. In this report 62% of families reported that low-dose topiramate (average dose of 30 mg/day) was successful in reducing both the frequency and severity of headache episodes. Campistol et al. [22] presented 24 children treated with topiramate for 4 months. And recorded a reduction in migraine frequency but this was not significantly different from baseline and significant differences in migraine severity and duration of the episodes. Our study revealed that 61% children had an excellent or good response. Cruz et al. [9] reported that 28 (76%) of children with migraine had an excellent or good response to topiramate. Topiramate was well tolerated and adverse effects occurred in 13 (23.6%) of the patients (five with parenthesis, four with drowsiness, and four with anorexia). Patients taking > 2 mg/kg/day were more likely to exhibit side effects: Eight of 13 were taking > 2 mg/kg/day, compared with children taking < 2 mg/kg/day (P = 0.042). There was a direct relationship between dosage and side effects. Another study, evaluating the safety, and tolerability of topiramate show that the most common side effects were paresthesia, weight loss, sleepiness, and worsened headaches. [21],[24] This study has several limitations. First, it was conducted at a single center with a smaller subject group. Another important fact that questionnaire were recalled from the patient's or parent's memory. Furthermore, larger, prospective studies are required to evaluate the long-term efficacy, tolerability, optimal dose, length of treatment, and long-term effects of topiramate in this population. In conclusion, 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.


   Acknowledgments Top


The authors kindly thank the Mazandaran University of Medical Science for financial support.

 
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