Vol 61: may • mai 2015
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Canadian Family Physician•Le Médecin de famille canadien435
Child Health Update
Abstract
Question I am seeing more and more children and adolescents with headaches that can be defined as migraine headache. I have read about intranasal sumatriptan as an abortive therapy. Is this an effective treatment?
Answer Acute migraine headache among children and adolescents is common and treatment is challenging.
Intranasal sumatriptan is a safe and mostly effective option for children and adolescents. Currently the recommended dose is 20 mg for children who weigh more than 40 kg and 10 mg for children who weigh between 20 and 39 kg. Larger trials should be conducted to overcome the limitations of small sample sizes, potential low plasma concentration, and placebo effects witnessed in studies to date.
This article is eligible for Mainpro-M1 credits. To earn credits, go to www.cfp.ca and click on the Mainpro link.
This article is eligible for Mainpro-M1 credits. To earn credits, go to www.cfp.ca and click on the Mainpro link.
La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de mai 2015 à la page 439.
M
igraine headache is common in children, with a mean age of onset of 7 years for boys and 11 years for girls, and a prevalence of 8% to 23% by 15 years of age.1-3 Migraine can cause substantial mor- bidity associated with missed school, reduced partici- pation in sports, and even depression.4,5The pathogenesis of migraine is multifactorial6 and diagnosis is made based on symptoms. (For more information, see the International Headache Society’s headache classifications.7)
Migraine treatment
Treatment of acute migraine in children is challenging,8 and despite published practice parameters,1 considerable practice variation has been observed.9,10 The goals of therapy are to abort an acute episode, eliminate pain, regain normal academic and physical activity, and reduce stress related to recurrent headaches for children and their families.11 The choice of drugs should take into account the pharmacokinetic and pharmacodynamic characteristics and safety profile of single or multidrug therapy.11
A range of pharmacologic agents have been used for acute abortive therapy in pediatric migraine, including nonsteroidal anti-inflammatory drugs and acetaminophen, triptans, and dopamine antagonists.
Evaluation of the effectiveness of these therapies in children is limited by the small number of randomized controlled trials and complicated by higher rates of placebo effect in children and adolescents compared with adults.12 However, in a recent single-blind,
randomized, parallel-arm trial with 45 children 5 to 17 years of age suffering a migraine-headache episode, creating an expectation that “a medication” would be given together with 10 mL/kg of intravenous 0.9% sodium chloride did not significantly influence reduction of headache at 30 minutes.13
The approach to migraine therapy includes acute symptomatic relief, as well as prevention of episodes with a combination of early pharmacologic abortive therapy and behavioural and lifestyle modifications (eg, adopting good sleep hygiene, exercising, eating a balanced diet, and avoiding known triggers).
Sumatriptan
A neurovascular cause leading to cranial vasodilation has been proposed for migraine, and serotonin (5-hydroxytryptamine [5-HT]) has been shown to inhibit this cascade. Elucidation of this process led to the development of a class of synthetic drugs, the triptans, that act as selective serotonin receptor agonists. Sumatriptan was the first triptan to be licensed for adults with migraine and is available in intravenous, oral, and intranasal formulations.
The exact mechanism of action of sumatriptan is not completely understood, but it is likely a result of the combined effect of serotonin receptor subtype stimulation: 5-HT1B receptor stimulation leads to vasoconstriction, while 5-HT1D receptor activation inhibits dural neurogenic inflammation, and receptor stimulation in the brainstem inhibits firing and sensitization in the trigeminal nuclei leading to possible analgesic effects.14,15
Intranasal sumatriptan for migraine in children
Ran D. Goldman
MD FRCPCGarth D. Meckler
MD436
Canadian Family Physician•Le Médecin de famille canadien|
Vol 61: may • mai 2015Child Health Update
Intranasal administration of drugs
Intranasal administration of drugs has been used for hundreds of years,16 and its effectiveness is a result of the easy access to the nasal mucosa, the rich vascular supply, and the rapid achievement of effective pharmacokinetic levels, possibly through first-pass hepatic metabolism circumvention.17,18 Intranasal delivery of medication has been documented to be effective for a number of indications (usually as “off label” therapy)19 including seizures20 and sedation.16 Because migraine has a high association with nausea and gastrointestinal symptoms that might lead to unreliable absorption of oral medications, the intranasal route of administration has theoretical advantages and is less invasive than subcutaneous or intravenous routes of medication delivery.
Intranasal sumatriptan for migraine
Intranasal sumatriptan is approved for the treatment of migraine with and without aura in adolescents in Europe, Asia, Australia, and Central America.15 In the United States, the Child Neurology Society recommends ibuprofen and acetaminophen for children 6 to 12 years of age and intranasal sumatriptan for adolescents older than 12 years of age.1
Before the turn of the century, Ueberall and Wenzel reported efficacy of up to 86% among 14 children 6 to 10 years old in a randomized, double-blind, placebo-
controlled crossover study using 20 mg of intranasal sumatriptan, showing a significant decrease in migraine pain intensity (P = .031).21 Shortly after, Winner et al reported intranasal sumatriptan to be effective and well tolerated among 653 adolescents 12 to 17 years of age with acute migraine with or without aura.22 The randomized, double-blind, placebo-controlled, single- attack study found that a significantly greater proportion of adolescents treated with 20 mg of sumatriptan achieved complete relief of headache at 2 hours compared with those receiving placebo (36% vs 25%;
P < .01). Migraine-related photophobia and phonophobia were also substantially reduced. In 2006, the same investigators studied 738 adolescents with a moderate or severe migraine episode and found that 20 mg of intranasal sumatriptan provided greater headache relief than placebo at 2 hours after treatment (68% vs 58%;
P = .025).23 In this study, and analysis of pooled data of the 2 studies, there was no significant difference between placebo and either 5-mg or 10-mg intranasal doses of sumatriptan. A third of participants needed rescue medications among all groups in this study.
In another double-blind, placebo-controlled, 2-way crossover trial from Finland,24 children 8 to 17 years of age seen in outpatient clinics received 10 or 20 mg of intranasal sumatriptan or placebo. Almost twice as many children in the sumatriptan group achieved
headache relief compared with those in the placebo group at 1 hour (51% vs 29%; P = .014) and at 2 hours (64% vs 39%; P = .003) posttreatment. As in other studies, a dose of 20 mg (as well as in the intention-to-treat analyses) was most effective. More than a third of children decided to take advantage of rescue analgesia that was offered, more so in the placebo group.
Two systematic reviews summarized the evidence on use of intranasal sumatriptan in children and adolescents and both concluded that intranasal sumatriptan was effective and well tolerated for the treatment of acute migraine in children and adolescents.25,26 In their 2007 review, Callenbach and colleagues reported the results of 7 studies of variable design, patient selection, and treatment regimens.26 They suggested that young children might have had a better response to sumatriptan than adolescents, perhaps as a result of higher plasma concentration (higher mg/kg dose for younger children).
Finally, in a meta-analysis of studies assessing treatment of acute migraine in children, Silver et al found ibuprofen and sumatriptan to be the only medications to have statistically significant efficacy when compared with placebo. Sumatriptan was reported to provide a relative benefit of 1.26 (95% CI 1.13 to 1.41) for reduction in headache pain (number needed to treat = 7.4) and a relative benefit of 1.56 (95% CI 1.26 to 1.93) in achieving complete pain relief (number needed to treat = 6.9).27
Safety
Intranasal administration of sumatriptan is generally safe with no serious drug-related adverse events or clinically relevant changes in laboratory values, cardiac conduction parameters, or vital signs. Taste disturbance was the most commonly reported adverse event in several studies (19% to 32% vs 2% with placebo).22-24 Less commonly reported side effects of intranasal sumatriptan include nausea (5%
to 11% vs 8% with placebo) and vomiting (3% to 5%
vs 2% with placebo).15
Conclusion
Treating acute migraine headache in children and adolescents is challenging, and despite the availability of several pharmacologic agents, very few options are proven to be clinically effective. Intranasal sumatriptan is a safe and mostly effective option for children and adolescents. Further research is needed in order to overcome the limitations of small sample sizes, potential low plasma concentration, and placebo effects witnessed in studies to date.
Competing interests None declared Correspondence
Dr Ran D. Goldman; e-mail [email protected]
Vol 61: may • mai 2015
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Canadian Family Physician•Le Médecin de famille canadien437
Child Health Update
References
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Pediatric Research in Emergency Therapeutics
Child Health Update is produced by the Pediatric Research in Emergency Therapeutics (PRETx) program (www.pretx.
org) at the BC Children’s Hospital in Vancouver, BC. Dr Meckler is a member and Dr Goldman is Director of the PRETx program. The mission of the PRETx program is to promote child health through evidence-based research in therapeutics in pediatric emergency medicine.
Do you have questions about the effects of drugs, chemicals, radiation, or infections in children? We invite you to submit them to the PRETx program by fax at 604 875- 2414; they will be addressed in future Child Health Updates. Published Child Health Updates are available on the Canadian Family Physician website (www.cfp.ca).
