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New Guidelines for Acute and Preventive Treatment of Pediatric Migraine: What You Should Know

Article In Brief

The lead author of two new guidelines on pediatric migraine prevention and treatment highlights the key findings for neurology practice.

Migraine is common in children and adolescents, with a prevalence of 1 percent to 3 percent in 3- to 7-year olds; 4 to 11 percent in 7- to 11-year-olds, and 8- to 23 percent by age 15, according to the authors of two new guidelines, one on preventive and the other on acute pharmacological treatment in children and teens, published in the August 16 online edition of Neurology.

But the process of determining the strength of the evidence for one therapeutic over another is all the more challenging, given the large placebo response reported in existing studies involving children and teens.

To update its 2004 practice parameter, the Guideline Development, Dissemination, and Implementation Subcommittee of the AAN and the American Headache Society reviewed studies from December 2003 to August 2017 and developed a set of practice recommendations using the AAN methodology for guideline development.

In an email interview with Neurology Today, the lead author, Maryam Oskoui, MD, MSc, associate professor in the departments of pediatrics and neurology neurosurgery at McGill University, highlighted some of the key findings of the updated review.

Why was an update to guidelines undertaken?

At the time of the 2004 practice parameter, there were few randomized controlled studies to support recommendations. Since then, new studies have been published on the efficacy and safety of migraine treatments. All of the AAN guidelines undergo a triennial review and are updated if new evidence is available that would affect the conclusions or recommendations.

What has changed since the practice parameter was issued?

Since the 2004 practice parameter, there is more evidence to support the use of triptans for acute symptoms. As well, in the 2004 guideline, there was insufficient evidence to make any recommendations on the use of amitriptyline, divalproex sodium, and topiramate for migraine prevention. There is more evidence now available for topiramate to guide clinical practice, though the evidence for amitriptyline and divalproex sodium remain insufficient. We also included studies evaluating cognitive behavioral therapy (CBT) in combination with preventive pharmacological treatments. We found good evidence of efficacy for combining cognitive behavior therapy with amitriptyline. The efficacy of and access to the use of CBT alone needs to be informed by future well-designed randomized controlled trials.

Can you describe your process, i.e., how the team assesses the different levels of evidence and its recommendations?

The first step is synthesizing the available evidence from our systematic review by anchoring the confidence level to the risk of bias assessment, leading to the terms possibly (low confidence) and probably (moderate confidence) in our evidence-based conclusions for each intervention outcome pair. These terms reflect our confidence that the estimate of the effect of an intervention is correct, in other words, they reflect our assessment of the accuracy of the evidence.

To create actionable recommendations that are useful in clinical practice, we then proceed to a higher-level evaluation of the evidence by putting it into a clinical context through a modified Grading of Recommendations Assessment Development and Evaluation (GRADE) process. This allows us to evaluate if the evidence is sufficient to support practice recommendations.

Our confidence in the evidence can then be potentially upgraded or downgraded based on several factors, such as a large magnitude of effect, a dose-response relationship, generalizability, biological plausibility, and other factors.

The guideline on preventive treatment found that children receiving propranolol “possibly” will have a 50 percent reduction in headache frequency. Would you elaborate on that finding?

The conclusion for propranolol was based on a single class II study from 1974 that included only 28 children. This was upgraded due to magnitude of effect, meaning that the few children in this study had a big response to treatment, leading to a possibly effective conclusion (low confidence in the evidence). Newer studies were not available to further guide practice. There are other treatments such as topiramate or combining amitriptyline with cognitive behavior therapy that have higher levels of evidence to support their use. Acknowledging the limitations of currently available evidence, clinicians should engage in shared decision making and discuss the evidence for these different treatment options and their side effects for those who could benefit from preventive treatment.

The preventive treatment guideline also suggests that children receiving topiramate “probably” will experience decrease in headaches. What is the strength of the evidence supporting this?

The evidence for topiramate efficacy is stronger for some outcomes only, with four class I studies showing it is probably more effective than placebo in reducing the number of headache days though this conclusion was downgraded due to imprecision. For other outcomes, such as reducing migraine-related disability, topiramate did not demonstrate a superior effect over placebo. Although topiramate is the only US Food and Drug Administration (FDA)-approved medication for migraine prevention in adolescents, the current evidence-base raises some doubts about whether this treatment achieves clinically meaningful outcomes beyond those obtained by placebo.

Figure

“The strongest available evidence is for combining amitriptyline with cognitive behavior therapy. Patients who were treated with this as compared with those treated with amitriptyline who receive headache education are more likely to have decreased migraine-associated disability.”—DR. MARYAM OSKOUI

The guidelines assessed some of the triptans? What were the findings as they apply to children and adolescents?

Many children and adolescents use and benefit from nonprescription oral analgesics like acetaminophen, ibuprofen, and naproxen for migraine relief. Only almotriptan (for patients aged 12 years and older), rizatriptan (for patients aged 6-17 years), sumatriptan/naproxen (for patients aged 12 years and older), and zolmitriptan NS (for patients aged 12 years and older) are approved by the FDA for use in children and adolescents. There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache free at two hours than those receiving placebo.

Are there pharmacological treatments the evidence strongly suggested were not effective?

The majority of randomized controlled trials that studied the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo, however none were unequivocally shown to be ineffective.

What was the strongest evidence for preventive therapies?

The strongest available evidence is for combining amitriptyline with cognitive behavior therapy. Patients who were treated with this as compared with those treated with amitriptyline who receive headache education are more likely to have decreased migraine-associated disability. There is insufficient evidence to judge the efficacy of amitriptyline alone, and it is possible that cognitive behavior therapy alone is effective in migraine prevention. Further studies are needed.

What is the take-home message for clinicians treating children with migraine?

Some treatments with proven efficacy in adults have not shown the same efficacy in children and adolescents and a higher pediatric placebo-response rate is observed. The presence of high placebo-response rates in pediatric migraine demonstrates that children respond to treatment of their headache but makes identifying a therapeutic response more challenging.

What else do you want readers of Neurology Today to know?

It is important to actively involve patients and parents in shared decision making, to identify clinically meaningful outcomes, assist with treatment adherence, and respect patient preferences.

Disclosures

Dr. Oskoui had nothing to disclose.

Link Up for More Information

• Oskoui M, Pringsheim T, Billinghurst, et al. Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention https://n.neurology.org/lookup/doi/10.1212/WNL.0000000000008105. Neurology 2019; Epub 2019 Aug 14.
    • Oskoui M, Pringsheim TT, Holler-Managan Y, et al. Practice guideline update summary: Acute treatment of migraine in children and adolescents https://n.neurology.org/lookup/doi/10.1212/WNL.0000000000008095. Neurology 2019; Epub 2019 Aug 14.