Does intranasal sumatriptan use relieve migraine in children and young people?
- 1Department of Paediatrics, Stoke Mandeville Hospital, Aylesbury, UK
- 2Department of Paediatrics, Oxford University Hospital, Oxford, UK
- Correspondence to Dr Geetha Anand, Oxford University Hospital, Oxford OX3 9DU, UK;
Contributors GA conceived the idea, and Bodlean Health Care Librarian, Liz Callow, performed the literature search. JY wrote the article and GA provided editing advice.
- Received 21 August 2012
- Revised 21 August 2012
- Accepted 29 August 2012
You are a paediatric registrar in clinic, and you see a 13-year-old boy with a recent diagnosis of migraine. His general practitioner has discussed options such as pizotifen, propranolol and topiramate, but his parents do not like the idea of him taking a medication daily. Ibuprofen has been tried at the onset of headaches, but has not worked. His parents wonder if there is any other medication that could be used when needed to relieve the pain. You have heard of intranasal triptans being used in adults and sometimes in older children. You decide to review the evidence.
Structured clinical question
In children over the age of 12 years with migraine (patient), does treatment with intranasal sumatriptan (intervention) reduce the pain (outcome) associated with migraine headache?
MEDLINE (1950–present) and Embase (1980–present) were searched via the OVID interface using the keywords ‘sumatriptan’ and ‘Migraine’. Limits included ‘human’ and English language articles only. Forty-seven articles were found, and four were found to be suitable.
Migraine is commonly seen in children and adolescents, and can have a significant effect on a child's quality of life and schooling.1 The pathophysiology of migraine is similar to that in adults with an interaction between neural and vascular systems. Triptans are 5-hydroxytryptamine receptor agonists (5-HT agonists) which work on 5-HT receptors in three possible ways; causing vasoconstriction, inhibiting dural neurogenic inflammation and plasma extravasation on trigeminal neurones, and in inhibiting firing of trigeminal nuclei.2
The pharmacological treatment of migraine can be categorised into acute and preventative treatment. The aim of acute treatment is the rapid return to normal function.1 Preventative treatment should be considered when headaches are frequent (more than once a week) with an aim to reducing the headache frequency to <1–2 per month, with a decreased disability for a sustained period of time (4–6 months).1 Currently, drugs used for the prevention of migraine which have been shown to be effective in preventing migraine include amitriptyline and trazodone (antidepressants), topiramate and divalproate (antiepileptics), and propranolol (antihypertensive).1
Few randomised controlled trials have evaluated the efficacy of medications used to treat acute migraine in children and adolescents.1 ,4 The effective acute drugs fall into two broad groups: non-steroidal anti-inflammatory drugs and triptans.
Intranasal sumatriptan is approved in Europe by the European Medicines Agency for the acute treatment of adolescent migraine (children aged >12 years).3 Oral triptans have variable absorption rates, and clinical effects which may be due to the delay in gastric emptying that occurs during migraine attacks,2 and are not routinely used in the treatment of migraine (table 2).
Silver et al 5 conducted a meta-analysis of 11 randomised, blinded, placebo-controlled studies on the acute pharmacologic treatment of children and adolescents with migraine headache; of which a total of five RCTs looked at sumatriptan (intranasal sumatriptan n=4, oral sumatriptan n=1). Sumatriptan (intranasal 20 mg, oral 50 mg) was associated with a greater degree of headache relief 2 h post-treatment compared with placebo, relative benefit (RB) 1.26 (95% CI 1.13 to 1.41), number needed to treat (NNT) 7.4 (5.0, 13.3); and more effectively produced complete pain relief 2 h following treatment in comparison with placebo, RB 1.56 (95% CI 1.26 to 1.93), NNT 6.9 (4.2, 11.5). A dose-response relationship was not reliably shown in any of the studies. Limitations of the meta-analysis are that the use of rescue medications was allowed in the RCTs by Winner et al 6 and Ahonen et al 7; additionally, the primary endpoint in one of the RCTs was only assessed in patients who completed both treatments, and the data were not reported on an intent-to-treat basis.7
Callenbach et al 8 performed a review of seven trials of intranasal sumatriptan compared with placebo in the treatment of migraine attacks in children and adolescents which highlighted the differences of study design, patient selection and treatment regimens. In three studies in adolescents, different dosages of sumatriptan were used without showing clear dosage-related differences in efficacy and the effects on the associated symptoms.6 ,8–10 In the study by Uberall et al 11 of children aged 6–9 years, the response rates for sumatriptan were much higher compared with those in the studies with adolescents, and sumatriptan had a larger effect on the associated symptoms. This may have been related to the fixed dose of 20 mg sumatriptan for all patients in this study, probably leading to higher plasma concentrations of sumatriptan in younger children.
High placebo responses have been reported by several randomised controlled trials.6 ,7 The study by Ahonen et al 7 reported that up to a third of children could taste the difference between sumatriptan and placebo, perhaps causing an unblinding effect in a crossover trial. However, taste disturbance with intranasal sumatriptan has not been found to have clinically significant effects or to have caused study withdrawal.6
Intranasal sumatriptan has been consistently shown to have statistically significant relative efficacy compared with placebo in the treatment of migraines in children,5 ,8 however, its efficacy has not been rigorously compared against conventional rescue medications. In fact, Ibuprofen has statistically significant relative efficacy compared with placebo as well as smaller NNT (NTT 2.4 in the generation of headache relief, NTT 4.9 in the production of complete pain relief).5 The evidence suggests that a trial of ibuprofen should thus be pursued prior to sumatriptan, given its smaller NNT in both outcomes and lower cost, following which intranasal sumatriptan has been shown to be beneficial in relieving migraine headache.5
Clinical bottom lines
Intranasal sumatriptan is beneficial in controlling migraines in children (Grade A), however, as this benefit is compared with placebo, it does not necessarily imply any benefit over other conventional treatments.
Taste disturbance is the most commonly noted adverse effect of intranasal sumatriptan (Grade B).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.