NIHR Signal “Triptans” can relieve migraines in children and adolescents

Published on 13 September 2016

Triptans, a migraine medication, relieve migraine headache completely within two hours compared to placebo. Ibuprofen was also effective but less well studied. This review was also reassuring in that any side effects of treatment were mild.

Most evidence identified in this Cochrane review was for sumatriptan, a commonly prescribed treatment for adults, compared to placebo or dummy pills. A few studies examined other triptans or other painkillers, such as ibuprofen or paracetamol against placebo in children and adults.

The findings support current guideline recommendations to prescribe nasal triptans for migraine in adolescents. Only nasal preparations are currently licensed for adolescents, whereas oral administration and use for children under 12 years, is an ‘off-label’ use. There were some mild adverse effects in the triptan groups that highlight the need for an informed discussion between clinicians and parents or patients and monitoring in this group.

“Triptans” can relieve migraines in children and adolescents

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Why was this study needed?

Migraines affect about 1 in 10 children of school age. Symptoms are similar to migraine in adults, with headache, nausea, vomiting and light sensitivity, but attacks are usually shorter, coming on quickly and lasting only a few hours. Young migraine sufferers may miss enough school to affect their education.

The number of migraines can be lessened by avoiding triggers, such as certain foods, but preventive treatments used for adults may not be suitable for children. The usual approach in children and young people is to treat the symptoms of migraine when they appear with pain-relief medications.

This systematic review is one of the few to look at the different adult treatments for acute migraine symptoms in under 17s.

What did this study do?

This Cochrane systematic review identified 29 randomised controlled trials comparing different migraine medications against placebo in 9158 children and adolescents aged eight to 15. Most studies (24) investigated the triptan group of painkillers, with half of all trials looking at sumatriptan specifically. Few studies looked at other treatments. The main outcome of interest was pain-relief by two hours.

Data quality was low to moderate: the risk of bias was judged to be low or unclear but there was inconsistency and imprecision in much of the data. Most of the included studies were sponsored by drug manufacturers (19 out of 27) and the authors reported some trial data were not available, which may affect the reliability of the results.

What did it find?

  • Triptans were more effective than placebo at relieving headache completely. For one to be pain free at two hours, six adolescents will need to be treated (relative risk [RR] 1.32, 95% confidence interval [CI] 1.19 to 1.47; 21 studies) and 13 children (RR 1.67, 95% CI 1.06 to 2.62; 3 studies). Nasally administered triptans were more effective against placebo when compared to oral triptans against placebo in two studies.
  • Ibuprofen was better than placebo at giving pain-relief by two hours in two small studies in children (RR 1.87, 95% CI 1.15 to 3.04), but no evidence for effect in a single study in adolescents. Paracetamol was not superior to placebo in one study in children. There were no studies in adolescents.
  • Sumatriptan plus naproxen (a non-steroidal anti-inflammatory, NSAID) was superior to placebo in one large study in 683 adolescents (RR 3.25, 95% CI 1.78 to 5.94).
  • There was an increased risk of minor adverse events in adolescents taking triptans (Risk difference 0.13, 95% CI 0.08 to 0.18) – with an estimated one person affected for every eight treated – but no risk increase in under 12s. There was no significant difference in adverse events between placebo groups and paracetemol, ibuprofen or sumatriptan plus naproxen.

What does current guidance say on this issue?

NICE guidance on headaches in over-12s recommends treating migraine symptoms with an oral triptan and an NSAID, or an oral triptan and paracetamol. Patient preference can be considered, and a nasal triptan may be preferred for young people aged 12 to 17.

When prescribing triptans, NICE recommend starting with the lowest price option, then switching to another if that proves ineffective. Anti-sickness medications are normally also needed alongside to manage nausea and vomiting.

What are the implications?

The largest body of evidence in this review was for triptans – the mainstay of migraine treatment in adults – finding that they were more effective than placebo in children and adolescents. Nasal triptans were more effective than oral triptans, supporting NICE guidance. There were fewer studies assessing other painkillers such as ibuprofen or paracetamol.

All studies compared treatments with placebo rather than with each other, so we cannot compare effects between drugs.

For clinicians, the choice of triptan medication may be guided by factors such as patient preference, route of delivery, or palatability. The researchers say that a parent who has already responded well to one of the medications themselves may be more likely to request that medication for their child.

Citation and Funding

Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database Syst Rev. 2016;4:CD005220.

Cochrane UK and the Pain, Palliative and Supportive Care Cochrane Review Group are supported by NIHR infrastructure funding.

Bibliography

NICE. Headaches in over 12s: diagnosis and management. CG150. London: National Institute for Health and Care Excellence; 2012.

The migraine trust. Home page. London: The migraine trust; 2016.

The migraine trust. Young sufferers. London: The migraine trust; 2016.

Migraine action. Migraine information. Leicester: Migraine action; 2016.

Why was this study needed?

Migraines affect about 1 in 10 children of school age. Symptoms are similar to migraine in adults, with headache, nausea, vomiting and light sensitivity, but attacks are usually shorter, coming on quickly and lasting only a few hours. Young migraine sufferers may miss enough school to affect their education.

The number of migraines can be lessened by avoiding triggers, such as certain foods, but preventive treatments used for adults may not be suitable for children. The usual approach in children and young people is to treat the symptoms of migraine when they appear with pain-relief medications.

This systematic review is one of the few to look at the different adult treatments for acute migraine symptoms in under 17s.

What did this study do?

This Cochrane systematic review identified 29 randomised controlled trials comparing different migraine medications against placebo in 9158 children and adolescents aged eight to 15. Most studies (24) investigated the triptan group of painkillers, with half of all trials looking at sumatriptan specifically. Few studies looked at other treatments. The main outcome of interest was pain-relief by two hours.

Data quality was low to moderate: the risk of bias was judged to be low or unclear but there was inconsistency and imprecision in much of the data. Most of the included studies were sponsored by drug manufacturers (19 out of 27) and the authors reported some trial data were not available, which may affect the reliability of the results.

What did it find?

  • Triptans were more effective than placebo at relieving headache completely. For one to be pain free at two hours, six adolescents will need to be treated (relative risk [RR] 1.32, 95% confidence interval [CI] 1.19 to 1.47; 21 studies) and 13 children (RR 1.67, 95% CI 1.06 to 2.62; 3 studies). Nasally administered triptans were more effective against placebo when compared to oral triptans against placebo in two studies.
  • Ibuprofen was better than placebo at giving pain-relief by two hours in two small studies in children (RR 1.87, 95% CI 1.15 to 3.04), but no evidence for effect in a single study in adolescents. Paracetamol was not superior to placebo in one study in children. There were no studies in adolescents.
  • Sumatriptan plus naproxen (a non-steroidal anti-inflammatory, NSAID) was superior to placebo in one large study in 683 adolescents (RR 3.25, 95% CI 1.78 to 5.94).
  • There was an increased risk of minor adverse events in adolescents taking triptans (Risk difference 0.13, 95% CI 0.08 to 0.18) – with an estimated one person affected for every eight treated – but no risk increase in under 12s. There was no significant difference in adverse events between placebo groups and paracetemol, ibuprofen or sumatriptan plus naproxen.

What does current guidance say on this issue?

NICE guidance on headaches in over-12s recommends treating migraine symptoms with an oral triptan and an NSAID, or an oral triptan and paracetamol. Patient preference can be considered, and a nasal triptan may be preferred for young people aged 12 to 17.

When prescribing triptans, NICE recommend starting with the lowest price option, then switching to another if that proves ineffective. Anti-sickness medications are normally also needed alongside to manage nausea and vomiting.

What are the implications?

The largest body of evidence in this review was for triptans – the mainstay of migraine treatment in adults – finding that they were more effective than placebo in children and adolescents. Nasal triptans were more effective than oral triptans, supporting NICE guidance. There were fewer studies assessing other painkillers such as ibuprofen or paracetamol.

All studies compared treatments with placebo rather than with each other, so we cannot compare effects between drugs.

For clinicians, the choice of triptan medication may be guided by factors such as patient preference, route of delivery, or palatability. The researchers say that a parent who has already responded well to one of the medications themselves may be more likely to request that medication for their child.

Citation and Funding

Richer L, Billinghurst L, Linsdell MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database Syst Rev. 2016;4:CD005220.

Cochrane UK and the Pain, Palliative and Supportive Care Cochrane Review Group are supported by NIHR infrastructure funding.

Bibliography

NICE. Headaches in over 12s: diagnosis and management. CG150. London: National Institute for Health and Care Excellence; 2012.

The migraine trust. Home page. London: The migraine trust; 2016.

The migraine trust. Young sufferers. London: The migraine trust; 2016.

Migraine action. Migraine information. Leicester: Migraine action; 2016.

Drugs for the acute treatment of migraine in children and adolescents

Published on 20 April 2016

Richer, L.,Billinghurst, L.,Linsdell, M. A.,Russell, K.,Vandermeer, B.,Crumley, E. T.,Durec, T.,Klassen, T. P.,Hartling, L.

Cochrane Database Syst Rev Volume 4 , 2016

BACKGROUND: Numerous medications are available for the acute treatment of migraine in adults, and some have now been approved for use in children and adolescents in the ambulatory setting. A systematic review of acute treatment of migraine medication trials in children and adolescents will help clinicians make evidence-informed management choices. OBJECTIVES: To assess the effects of pharmacological interventions by any route of administration versus placebo for migraine in children and adolescents 17 years of age or less. For the purposes of this review, children were defined as under 12 years of age and adolescents 12 to 17 years of age. SEARCH METHODS: We searched seven bibliographic databases and four clinical trial registers as well as gray literature for studies through February 2016. SELECTION CRITERIA: We included prospective randomized controlled clinical trials of children and adolescents with migraine, comparing acute symptom relieving migraine medications with placebo in the ambulatory setting. DATA COLLECTION AND ANALYSIS: Two reviewers screened titles and abstracts and reviewed the full text of potentially eligible studies. Two independent reviewers extracted data for studies meeting inclusion criteria. We calculated the risk ratios (RRs) and number needed to treat for an additional beneficial outcome (NNTB) for dichotomous data. We calculated the risk difference (RD) and number needed to treat for an additional harmful outcome (NNTH) for proportions of adverse events. The percentage of pain-free patients at two hours was the primary efficacy outcome measure. We used adverse events to evaluate safety and tolerability. Secondary outcome measures included headache relief, use of rescue medication, headache recurrence, presence of nausea, and presence of vomiting. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. MAIN RESULTS: We identified a total of 27 randomized controlled trials (RCTs) of migraine symptom-relieving medications, in which 9158 children and adolescents were enrolled and 7630 (range of mean age between 8.2 and 14.7 years) received medication. Twenty-four studies focused on drugs in the triptan class, including almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, sumatriptan + naproxen sodium, and zolmitriptan. Other medications studied included paracetamol (acetaminophen), ibuprofen, and dihydroergotamine (DHE). More than half of the studies evaluated sumatriptan. All but one study reported adverse event data. Most studies presented a low or unclear risk of bias, and the overall quality of evidence, according to GRADE criteria, was low to moderate, downgraded mostly due to imprecision and inconsistency. Ibuprofen was more effective than placebo for producing pain freedom at two hours in two small studies that included 162 children (RR 1.87, 95% confidence interval (CI) 1.15 to 3.04) with low quality evidence (due to imprecision). Paracetamol was not superior to placebo in one small study of 80 children. Triptans as a class of medication were superior to placebo in producing pain freedom in 3 studies involving 273 children (RR 1.67, 95% CI 1.06 to 2.62, NNTB 13) (moderate quality evidence) and 21 studies involving 7026 adolescents (RR 1.32, 95% CI 1.19 to 1.47, NNTB 6) (moderate quality evidence). There was no significant difference in the effect sizes between studies involving children versus adolescents. Triptans were associated with an increased risk of minor (non-serious) adverse events in adolescents (RD 0.13, 95% CI 0.08 to 0.18, NNTH 8), but studies did not report any serious adverse events. The risk of minor adverse events was not significant in children (RD 0.06, 95% CI - 0.04 to 0.17, NNTH 17). Sumatriptan plus naproxen sodium was superior to placebo in one study involving 490 adolescents (RR 3.25, 95% CI 1.78 to 5.94, NNTB 6) (moderate quality evidence). Oral dihydroergotamine was not superior to placebo in one small study involving 13 children. AUTHORS' CONCLUSIONS: Low quality evidence from two small trials shows that ibuprofen appears to improve pain freedom for the acute treatment of children with migraine. We have only limited information on adverse events associated with ibuprofen in the trials included in this review. Triptans as a class are also effective at providing pain freedom in children and adolescents but are associated with higher rates of minor adverse events. Sumatriptan plus naproxen sodium is also effective in treating adolescents with migraine.

The individual triptans included in this review were almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan.

An unlicensed medicine is a medicine that does not have a UK marketing authorisation.

An off-label medicine is a medicine with an existing UK marketing authorisation that is used outside the terms of its marketing authorisation, for example, by indication, dose, route or patient population.

Expert commentary

Although over 10% of children and adolescents suffer with migraine, the majority go unrecognised and untreated. Paracetamol and ibuprofen, together with a prokinetic is a good starting point. It is reassuring that the safety profile of triptans is confirmed, however, only the nasal preparation of sumatriptan is licensed and only for those over 12 years of age. Nevertheless, the BNF lists oral sumatriptan from the age of six years upwards for off-licence use. GPs should feel confident to prescribe oral triptans above the age of 12 but prescribing in a younger group is best left to specialist practice. An important practical point is that failure of response to one triptan is not a class effect.

Dr David Kernick, GP with a special interest in headache, Exeter

Expert commentary

The need for more research on the acute treatment of migraine in children and adolescent has been shown clearly in this systematic review. Conducting clinical trials in young children can be challenging and more so if the drugs in question are old and well established. Research on paracetamol and ibuprofen is needed not only to establish their efficacy, but also to identify the optimum dosages. Nasal sumatriptan and other triptans (to a lesser degree) are shown here to provide good options in the treatment of migraine in adolescents, but further research is need for their role in younger children.

Dr Ishaq Abu-Arafeh, Consultant in Paediatrics and Paediatric Neurology, Royal Hospital for Children, Glasgow