Topiramate in the Prophylaxis of Pediatric Migraine: A Double-Blind Placebo-Controlled Trial

Abstract

Several large, randomized controlled trials have demonstrated the efficacy of topiramate in migraine prophylaxis in adults. However, there are limited data about the use of topiramate in migraine prophylaxis in children. We conducted this single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate in the prophylaxis of migraine in children. A total of 44 children with migraine were randomized using random number tables to receive topiramate (n = 22) or placebo (n = 22). The total duration of treatment was 4 months, including a baseline period of 1 month during which topiramate was titrated weekly in 25-mg increments to 100 mg/d in 2 divided doses or to the maximum tolerated dose. The titration was followed by a 12-week maintenance phase during which topiramate was given in 2 divided doses. The primary outcome measures were the reduction in the mean migraine frequency and severity of headache. Secondary outcome measures included the number of times analgesics were required for a month for acute attacks and functional disability. Functional disability was measured by comparing school absenteeism and Pediatric Migraine Disability Assessment Scale (PedMIDAS). The decrease in mean (±SD) monthly migraine frequency from 16.14 (±9.35) at baseline to 4.27 (±1.95) at the end of the study in the topiramate group was significantly greater as compared with a decrease from 13.38 (±7.78) to 7.48 (±5.94) at the end of the study in the placebo group (P = .025). The difference in number of rescue medications used for topiramate and placebo was not statistically significant (P = .059). There was a statistically significant decrease in the PedMIDAS score from 50.66 (±32.1) to 10.42 (±6.39) at the end of the study in the topiramate group compared with a decrease from 42.66 (±27.5) to 23.7 (±19.1) at the end of 4 months in the placebo group (P = .003). The decrease in school absenteeism was significant with topiramate compared with placebo (P = .002). Weight loss, decreased concentration in school, sedation, and parasthesias were important side effects with topiramate. Most of these side effects were mild to moderate and were not significant enough to cause dropout from the study.

Keywords

topiramate migraine pediatric children headache PedMIDAS

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References

Hershey AD , Powers SW , Vockell Alb , LeCates S. , Kabbouche M. Effectiveness of Topiramate in the prevention of childhood headaches. Headache. 2002;42:810-818.

Shivpuri D. , Rajesh MS , Jain D. Prevalence and characteristics of migraine among adolescents: questionnaire survey. Indian Pediatr. 2003;40:665-669.

Frare M. , Axia G. , Batistella PA Quality of life, coping strategies and family routines in children with headaches . Headache. 2002;42:453-462.

Silberstein SD Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754-762.

Limmroth V. , Katsarava Z. , Fritsche G. , Przywara S. , Diener HC Features of medication overuse headache following overuse of different acute headache drugs. Neurology. 2002;59:1011-1014.

Vasconcellos E. , Pina-Garza JE , Millan EJ , Warner JS Analgesic rebound headache in children and adolescents. J Child Neurol. 1998;13:443-447.

Duke University Centre for Clinical Health Policy Research. Drug Treatments for the Prevention of Migraine Headache. Publication No. 290-94-2025 (Technical review 2.3). Springfield, Va: US Department of Commerce; 1999.

Linde K. , Rossnagel K. Propranolol for migraine prophylaxis. Cochrane Database Syst Rev. 2004;(2):CD003225.

Gray RN , Goslin RE , McCrory DC , Eberlein K. , Tulsky J. , Hasselblad V. Drug Treatments for the Prevention of Migraine. Technical review 2.3. February 1999. Prepared for the Agency for Health Care Policy and Research under Contract No. 290-94-2025.

10.

Evers S. Drug treatment of migraine in children. Pediatr Drugs. 1999;1:7-18.

11.

Gawel MJ , Kreeft J. , Nelson RF , Simard D. , Arnott WS Comparison of the efficacy and safety of flunarizine to propranolol in the prophylaxis of migraine. Can J Neurol Sci. 1992; 19:340-345.

12.

Sorge F. , Marano E. Flunarizine vs. placebo in childhood migraine. A double-blind study. Cephalalgia. 1985;5(suppl 2): 145-148.

13.

Sorge F. , DeSimone R. , Marano E. , et al. Flunarizine in prophylaxis of childhood migraine. A double blind, placebo-controlled crossover study. Cephalalgia. 1988;8:1-6.

14.

Guidetti V. , Moscato D. , Ottaviano S. , et al. Flunarizine and migraine in childhood: an evaluation of endocrine function. Cephalalgia. 1987;7:263-266.

15.

Lutschg J. , Vassella F. The treatment of juvenile migraine using flunarizine or propranolol. Schweiz Med Wochenschr. 1990;120: 1731-1736.

16.

Porthmann R. Calcium-antagonist flunarizine vs. low dose acetyl salicylic acid in childhood migraine: a double blind study. Cephalalgia. 1987;7(suppl 6):385-386.

17.

Castellana M. , Carini U. , Caprici G. , et al. Calcium entry blockers in the treatment of primary headache in childhood: our experience with flunarizine and Nimodipine . In: Proceedings of the First International Symposium on Headache in Children and Adolescents. New York: Elsevier; 1989:349-352.

18.

Sorensen PS , Larsen BH , Rasmussen MJ , et al. Flunarizine versus metoprolol in migraine prophylaxis: a double-blind, randomized parallel group study of efficacy and tolerability. Headache. 1991;31: 650-657.

19.

Snow V. , Weiss K. , Wall EM , Mottur-Pilson C. , American Academy of Family Physicians, American College of Physicians-American Society of Internal Medicine. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002;137:840-849.

20.

Chronicle E. , Mulleners W. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev. 2004;(3):CD003226.

21.

Shuaib A. , Ahmed F. , Muratoglu M. , Kochanski P. Topiramate in migraine prophylaxis: a pilot study. Cephalalgia . 1999;19: 379-380.

22.

Wheeler SD , Carrazana EJ Topiramate treated cluster headache. Neurology. 1999;53:234-236.

23.

Philipps TM , Bates Srd , Rudnicki SA Prophylaxis of pediatric headache with Topiramate [abstract]. Neurology. 2003: 60(suppl 1):A44.

24.

Farreira J. , Garcia N. , Pedeira L. A Case Series of Topiramate in Pediatric and Adolescent Migraine Prophylaxis . Presented at: American Academy of Neurology Annual Meeting; April 13-20, 2002; Denver, Colo (Abstract P06.119).

25.

Younkin DP Topiramate in the treatment of pediatric migraine [abstract]. Headache. 2002;42:456.

26.

Winner P. , Pearlman EM , Linder SL , Jordan DM , Fisher AC , Hulihan J. Topiramate for migraine prevention in children: a randomised, double-blind, placebo-controlled trial. Headache. 2005;45:1304-1312.

27.

Shank RP , Gardocki JF , Streeter AJ , Maryanoff BE An overview of the preclinical aspects of Topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000; 41(suppl 1):S3-S9.

28.

Classification Committee for the International Headache Society. Headache The International classification of headache disorders. Cephalalgia. 2004;24:1-160.

29.

Hershey AD , Powers SW , Vockell Alb , LeCates S. , Kabbouche M. , Maynard MK PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001; 57:2034-2039.

30.

Silberstein SD , Neto W. , Schmitt J. , Jacobs D. , for the MIGR-001 Study Group. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490-495.

31.

Brandes JL , Saper JR , Diamond M. , et al, for the MIGR-002 Study group. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;291:965-973.

32.

Diener HC , Tfelt-Hansen P. , Dahlot C. , et al, for the MIGR-003 Study group. Topiramate in migraine prophylaxis: results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943-950.

33.

Winner P. , Pearlman EM , Linder SL , Jordan DM , Fischer AC , Hulihan J. Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache. 2005;45:1304-1312.

34.

Martinez HR , Londono O. , Martinez LC , Tarin LC , Castillo CD Topiramate as an adjunctive treatment in migraine prophylaxis. Headache. 2003;43:1080-1084.

35.

Storey JR , Calder CS , Hart DE , Potter DL Topiramate in migraine prevention: a double-blind placebo controlled study . Headache. 2001;41:968-975.

36.

Mathew NT , Kailasam J. , Meadors L. Prophylaxis of migraine, transformed migraine and cluster headache with Topiramate . Headache. 2002;42:796-803.