AAN, AHS Release New Guidelines on Pediatric Migraine

Damian McNamara

September 04, 2019

For the first time since 2004, the American Academy of Neurology (AAN) and the American Headache Society (AHS) have updated two guidelines for acute treatment and prevention of migraines in children and adolescents.

New to the 2019 guidelines are evidence for using certain triptan-nonsteroidal anti-inflammatory drug (NSAID) combinations for acute pain relief; incorporation of more recently approved triptan nasal sprays; and indications that cognitive-behavioral therapy (CBT) plus amitriptyline can be beneficial for the prevention of chronic migraine.

The guidelines show that "NSAIDs work in kids — ibuprofen and naproxen sodium," senior guideline author Andrew D. Hershey, MD, PhD, endowed chair and director of neurology and director of the Headache Center at Cincinnati Children's Hospital Medical Center, Ohio, told Medscape Medical News.

In addition, "triptans can be added, either in combination or alone. The guidelines don't have all the triptans studied but do have clear evidence that they work for the ones studied," he said.

"In the broadest strokes, the guidelines help expand and confirm the principles used to treat children and adolescents," Hershey added.

The acute treatment guidelines and the migraine prevention guidelines were published online August 14 in Neurology.

Evidence-Based Treatments

Coauthor Kenneth J. Mack, MD, PhD, professor of neurology and pediatrics and chair in the Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minnesota, noted that the new guidelines incorporate an additional 15 years of published experience.

"During that time, we have seen the growth in the use of triptans for young children, and that is reflected in the new acute therapy guidelines," Mack said.

A 15-member expert subcommittee of the AAN and the AHS conducted a systematic review of the literature. They ranked their confidence in the evidence from "very low" to "high." They also assessed various agents in terms of pain response at 30 minutes, 1 hour, and 2 hours after onset of a migraine.

"We reviewed all of the available evidence, and the good news is that there are [new] evidence-based treatments for children and teens that are effective for treating migraine attacks when they occur," guideline lead author Maryam Oskoui, MD, McGill University, Montreal, Canada, and a fellow of the AAN, said in a statement.

For example, there was "high confidence in the evidence" that, in comparison with placebo, the following acute treatments would enable adolescents to be pain free at 2 hours: sumatriptan 10 mg/naproxen OT 60 mg; the same combinations at 30 mg/180 mg and 85 mg/500 mg; and zolmatriptan nasal spray 5 mg.

The prevention guidelines point out that a combination of CBT and amitriptyline was more effective than amitriptyline and headache education in reducing migraine-related disability and the frequency of attacks.

Although the authors caution that amitriptyline could increase the risk for suicidal thoughts and behavior, Hershey noted that "CBT-amitriptyline has clear evidence" supporting its use for chronic migraine.

"This opens the door for additional need for prevention therapy, but that CBT should be an integral part of the treatment plan when the headaches are frequent," added Hershey, who is also professor of pediatrics and neurology at the University of Cincinnati College of Medicine.

"The general consensus was that a multidisciplinary approach that incorporates acute and preventive treatments — this includes CBT — and healthy habits is recommended," he said.

"I think that the preventive guideline also emphasizes a multidisciplinary or perhaps holistic approach to young people with migraines," Mack added.

The experts also assessed migraine-related symptoms and found no effective treatments for nausea or vomiting. However, they did find that some triptans appear effective for migraine-related phonophobia and photophobia.

Problematic Placebo Effect

Evidence in support of medication to prevent these debilitating headaches in pediatric patients is weaker than evidence from the acute treatment trials, in part because of a strong placebo effect reported in many preventive therapy studies.

For example, the Childhood and Adolescent Migraine Prevention (CHAMP) study "demonstrated that all three arms were effective: amitriptyline, topiramate, and placebo," Hershey said.

This placebo effect likely occurs because studies involving children and adolescent are conducted after adult studies have demonstrated efficacy, he added. "This creates a higher degree of 'expectation' response," he said.

The bottom line is that a "new study design is likely to be required once a medication is approved for trials later performed, like those in children and adolescents, to alter the expectation curve," he said.

New medications that were not included in the guidelines are the calcitonin gene-related peptide (CGRP) antibodies, which continue to generate a lot of attention for migraine treatment in adults.

"Currently, the CGRP antibody studies in adolescents and children are in development, but it will be several years before the efficacy studies are completed," Hershey said. "Thus, they could not be included in these guidelines."

Injections of botulinum toxin, which also demonstrate efficacy in many adult studies, have not been found to have the same efficacy in children and adolescents.

"There is the hope for new agents, but there is also skepticism that although they may work, the expectation/placebo will minimize the observed difference," Mack said. This is likely the explanation for botulinum toxin studies, which also have been observed not to work in adolescents, he added.

The practice guideline was developed with financial support from the AAN. Oskoui has reported no relevant financial relationships. Mack has served as an advisor for AMGEN, receives publishing royalties from UpToDate, performs botulinum toxin injections for headache treatment as 5% of his clinical effort, and serves as a member of the Neurology editorial board. Hershey has served on a scientific advisory board for Allergan, XOC Pharma, and Amgen; has served as an editor for Headache, Cephalalgia, and the Journal of Headache and Pain; has received compensation from Allergan and MAP Pharma; currently receives compensation from Alder, Amgen, Avanir, Curelator, Depomed, Impax, Lilly, Supernus, and Upsher-Smith for serving on speakers' bureaus and as a medical consultant; has received research support from GlaxoSmithKline, the Migraine Research Foundation, Curelator, Inc, and the National Headache Foundation; has received study grants from the National Institutes of Health/National Institute of Neurologic Disorders and Stroke; and serves as a board member of the AHS.

Neurology. Published online August 14, 2019. Acute treatment abstract; Prevention abstract

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