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Three Part Question

In [children with migraine] is [topiramate effective] at [reducing frequency of attacks]?

Clinical Scenario

A 13 year old girl attends outpatients with frequent migraines. She has tried pizotifen and propranolol for migraine prophylaxis but was unable to tolerate the side effects. You have heard about topirmate for this indication and wonder whether it may help.

Search Strategy

Dialog Datastar Interface
MEDLINE (1950 - date): (migrain$ OR headache$) AND (topiramate OR topamax) AND LG=EN AND HUMAN=YES AND (CHILD# OR ADOLESCENT.DE. OR INFANT#)
EMBASE (1974 - date): (migrain$ OR headache$) AND (topiramate OR topamax) AND LG=EN AND HUMAN=YES AND CHILD=YES

Search Outcome

MEDLINE: 66 papers
EMBASE: 184 papers
4 were found to be relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Winner et al. 2005 USA	162 children aged 6-15 years with migraine meeting the IHS classification of pediatric migraine and weighing more than 20kg recruited from 17 centres. 131 patients completed the trial. 157 were eligible for ITT analysis.	Randomised, double-blind, placebo-controlled trial	Overall reduction of migraine-days per month	Topiramate group experienced a mean reduction of 2.6 migraine-days per month, compared with 2.0 for placebo group (P=0.61)	No power calculation Outcome averaged across entire study duration - prophylactic effect may take time to manifest
			>75% reduction of mean monthly migraine days	32% of topiramate treated patients experienced a >75% reduction in mean monthly migraine days compared to 14% of placebo-treated patients (P=0.02)
Winner et al. 2006 USA	51 children aged 12-17 enrolled in 3 larger pivotal trials of topiramate 50mg, 100mg and 200mg for migraine prophylaxis	Post hoc subset efficacy analysis of 3 randomised, double-blind, placebo-controlled trials	Reduction in monthly migraine frequency from baseline	Topiramate treatment with 50mg, 100mg and 200mg reduced monthly migraine frequency from baseline by 46%(P=0.07), 63%(P=0.02) and 65%(P=0.04) respectively compared with placebo (16%)	Small sample size
			Reduction in mean monthly migraine days	Topiramate 50mg, 100mg and 200mg reduced monthly migraine days by 1, 4 and 5 days compared with 1 day for placebo (NS)
Hershey et al 2002 USA	97 children under 19 years reporting >3 headaches/month. Headaches diagnosed according to IHS criteria and clinical impression.	Prospective, nonblinded open-label trial	Reduction in headache frequency in days per month at subsequent follow-up as clinically indicated	Mean headache frequency reduced from 16.5 days/month to 11.6 days/month at first follow-up(P<0.001), followed by further reduction to 9.4 days/month at second follow-up (P<0.001)	Diagnosis of frequent headache rather than migraine. No placebo. Topiramate was part of a bio-behavioural program for headache management so its individual effect is unclear.
			Pediatric Migraine Disability Assessment score	Reduction in mean score from 36 to 20.8 at first follow-up(P<0.05), 19.1 at second follow-up(P<0.005), and 10.9 at third follow-up(P<0.001)
Campistol et al. 2004 USA	24 children diagnosed with IHS criteria-based migraine refractory to other prophylactics. 22 Children completed 4 months of treatment.	Open, prospective multicentre case series	Duration of headache	87.5% reported a decrease	No placebo.

Comment(s)

Migraine is a relatively common problem to paediatric practice and frequent migraine attacks impact negatively on school attendance and family dynamics. Propranolol and flunarizine(not available in the UK) are the only two drugs that have been shown to improve headache frequency but trials of other drugs have suffered from considering small numbers of patients and thus being underpowered. Topiramate has been shown to be effective in reducing headache frequency in adults although there has been concern about its side effect profile. Much of the adverse event data, however, is based on findings from its use as an anticonvulsant, where much higher drug doses are used. The studies identified show that topiramate appears to demonstrate modest reduction in headache frequency in children with migraine, but all are to a greater or lesser extent methodologically flawed.

Clinical Bottom Line

Topiramate shows significant promise for migraine prophylaxis in children. A methodologically-robust, adequately-powered RCT is required to demonstrate its efficacy. Until such a study is performed, there is enough evidence to justify a therapeutic trial of topiramate in children with migraine who fail to respond to currently accepted first-line prophylactic therapy.

References

1. Winner P, Pearlman EM, Linder SL, Jordan DM, Fisher AC, Hulihan J for the Topiramate Pediatric Migraine Study Investigators Topiramate for Migraine Prevention in Children: A Randomized, Double-Blind, Placebo Controlled Trial Headache 2005;45:1304-1312
2. Winner P, Gendolla A, Stayer C, Wang S, Yuen E, Battisti WP, Nye JS Topiramate for Migraine Prevention in Adolescents: A Pooled Analysis of Efficacy and Safety Headache 2006;46:1503-1510
3. Hershey AD, Powers SW, Vockell A-LB, LeCates S, Kabbouche M Effectiveness of Topiramate in the Prevention of Childhood Headaches Headache 2002;42:810-818
4. Campistol J, Campos J, Casas C, Herranz JL Topiramate in the prophylactic treatment of migraine in children J Child Neurol 2005;20:251-3.