Migraine affects 10% of the world population [1].
An Indian study showed that migraine affects 14% of girls and 9% of boys
in 11-15 year age group [2]. Most preventive pharmacotherapies have
limited efficacy and are effective in less than half of the total cases
[4].
Topiramate is a neurmodulatory compound with neuron
stabilizing properties and is approved for the preventive treatment of
migraine in several countries
[5]. Several small and large trials have reported good
efficacy and safety of topiramate in migraine prophylaxis in adults [6].
The present study was done to study the role of topiramate in migraine
prophylaxis in children who either failed to respond to or were
intolerant to other prophylactic medications used for migraine.
Twenty-two patients, attending the Neurology
outpatients of a tertiary care hospital and having at least a 6-month
history of migraine with 3-12 attacks per months were enrolled for the
study. The patients were recruited if they met the International
Headache Society (IHS) criteria for diagnosis of migraine and were
excluded if they experienced headache other than migraine, had late
onset migraine or renal stones. Patients were also excluded if they had
more than 15 attacks of migraine per month or were given topiramate for
any other indications. A wash out period of 14 days was given during
which rescue analgesics of NSAID class (e.g. ibuprofen 6mg/kg) was
allowed.
Patients were prescribed tablet topiramate 15 mg/day
and titrated over 8 weeks to 2 mg/kg or maximum tolerated dose,
whichever was less. The patients were asked to report after third month.
A responder was defined as a patient who achieved at least 50% reduction
in monthly migraine attacks.
Headache severity was graded on a 4 point scale
ranging from grade 3, severe, requiring rest in bed; grade 2 moderate
reduced capacity; grade 1, mild but not interfering with working
capacity; and, grade 0, none, able to work or function normally. The
primary efficacy was judged by reduction in mean migraine frequency
across 12-weeks study period. Baseline (0 day) and endpoint assessment
(3 months) of the patients was done. Headache Intensity was rated on a
10-point Visual Analogue Scale where 0 represented no pain and 10
represented the most severe pain (Table I). Patients were
asked to keep a daily diary of their migraine attacks and associated
symptoms like nausea, vomiting and aura. Safety was assessed by
observing the treatment emergent side effects. Patients and parents were
encouraged to report any treatment related side effects or report any
new symptom following drug intake.
TABLE I Severity of Migraine Symptoms Before and After Topiramate (n=18)
|
Baseline |
After 3 months |
Frequency mean ± (SD) |
5.3 (1.5) |
1.0 (0.3)* |
Severity
|
18 |
14 (77.77%)
|
Nausea, n (%) |
12 (66.6) |
4 (22.2 ) |
Vomiting, n (%) |
10 (55.5) |
2 (11.1 )
|
Aura, n (%)
|
5 (27.7)
|
1 (5.5 )
|
n=number of patients, *P < 0.05 |
Baseline (0 day) routine hematological investigations
(total and differential leukocyte count), urine analysis (microscopic),
blood urea, creatinine, and liver function tests were done. Fisher Exact
test and Chi square tests were used for statistical analysis with P<0.05
considered as significant.
Four patients were lost to follow up. Fourteen out of
18 patients (M:F 4:14 mean age 11.2 years, mean migraine duration: 1.2
years) had statistically significant reduction in severity of headache
and migraine associated symptoms. Side effects reported were mild and
included anorexia in 2, and paresthesia and impaired concentration in 1
each. None of the patient opted out of the study due to side effects.
In the present study, 77.7% of 18 children had
significant pain relief, and reduction in severity of headache and
migraine associated symptoms. In a prospective case series of 24
children diagnosed with migraine refractory to prophylactics and treated
for 4 months with topiramate as the only prophylactic drug [7], the drug
was found to be safe and effective. In another similar study [8]
severity and duration of headache were also reduced. Headache disability
improved, with a reduction of PedMIDAS scores.
This is consistent with earlier studies [7,9,10]. We
used the maintenance dose of 2 mg/kg/day as earlier described [10].
These authors reported a 75% of greater reduction in mean migraine
frequency in 32% of the 160 children studied. Higher response rate in
our study could be due to small sample size or because we defined a
responder as the patient having 50% or more reduction.
Topiramate was found to be a safe, efficacious and
well tolerated drug in migraine prophylaxis in children.
Funding: None; Competing interests: None
stated.
References
1. Leonardi M, Steiner TJ, Scher AT, Lipton RB. The
global burden of migraine: measuring disability in headache disorders
with WHO’s Classification of Functioning, Disability and Health (ICF). J
Headache Pain. 2005: 429-40.
2. Shivpuri D, Rajesh MS, Jain D. Prevalence and
characteristics of migraine among adolescents: a questionnaire survey.
Indian Pediatr. 2003;40:665-9.
3. Buchanan TM, Ramadan NM. Prophylactic
pharmacotherapy for migraine headaches. Semin Neurol. 2006; 26:188-98.
4. Goadsby PJ, Lipton RB, Ferrari MD.
Migraine-current understanding and treatment. N Engl J Med.
2002;346:257-69.
5. Bussone G, Usai S, D’Amico D. Topiramate in
migraine prophylaxis: data from a pooled analysis and open-label
extension study. Neurol Sci. 2006; Suppl 2:S159-63
6. Rapoport A, Mauskop A, Diener HC, Schwalen S,
Pfeil J. Long-term migraine prevention with topiramate: open-label
extension of pivotal trials. Headache. 2006;46:1151-60.
7. Campistol J, Campos J, Casas C, Herranz JL.
Topiramate in the prophylactic treatment of migraine in children. J
Child Neurol. 2005;20:251-3.
8. Hershey AD, Powers SW, Vockell AL, LeCates S,
Kabbouche M. Effectiveness of topiramate in the prevention of childhood
headaches. Headache. 2002;42:810-8.
9. Silberstein SD. Topiramate in migraine prevention.
Headache. 2005;45 Suppl 1:S57-65.
10. Winner P, Pearlman EM, Linder SL, Jordan DM,
Fisher AC, Hulihan J; Topiramate Pediatric Migraine Study Investigators.
Topiramate for migraine prevention in children: a randomized,
double-blind, placebo-controlled trial. Headache. 2005;45:1304-12.
|