Research Reinforces Alternatives to Medication in Migraine Care

Research By Scott Powers, PhD, Andrew Hershey, MD, PhD

Post Date: July 27, 2021 | Publish Date: July 12, 2021

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Photo courtesy of Theranica

One study led by experts at Cincinnati Children’s bolsters use of cognitive behavior therapy for prevention, two others find value in a device for treatment once headache strikes

Migraine in children and teens is more common than many may realize. About 10% of all school-age children experience headaches due to migraine, while it impacts nearly one-third of teens aged 15 to 19, according to the Migraine Research Foundation.

Unlike adults, medications have struggled to demonstrate effectiveness over placebo in children and adolescents with migraine. However, cognitive behavior therapies (CBT) to help prevent headache onset and a new wearable device used once an attack of migraine starts are showing benefits that avoid the possible side effects of medications, according to recent studies led by experts at Cincinnati Children’s.

“Our findings suggest that the chemicals in the pills likely have little to nothing to do with achieving improved migraine control,” says Scott Powers, PhD, Co-Director of the Headache Center at Cincinnati Children’s.

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Scott Powers, PhD

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Andrew Hershey, MD, PhD

On July 12, 2021, experts at Cincinnati Children’s and the University of Iowa published a three-year follow-up study in JAMA Network Open to a migraine study published in 2017 in The New England Journal of Medicine. The earlier study reported results from a 31-center clinical trial called CHAMP, which found that a placebo produced just as much benefit as the two most-commonly-prescribed migraine medications: topiramate and amitriptyline.

The new study reports that CHAMP participants maintained the improvements they gained from treatments received even after they stopped taking the medications or the placebo. The principal co-authors were Powers; Christopher Coffey, PhD, University of Iowa; and Andrew Hershey, MD, PhD, Endowed Chair and Director of Neurology at Cincinnati Children’s and Co-Director of the Headache Center.

How could this be? Co-authors say the most likely explanation is by simply participating in the CHAMP study the youths gained deeper understanding of their migraine and learned how to adjust their behaviors and healthy habits to manage the headaches—such as striving to get enough sleep and good hydration.

“Regardless of treatment group (amitriptyline, topiramate, placebo), youth consistently maintained meaningful reductions of headache days and migraine-related disability for three years after completion of the trial,” the new study states. “Less than 10% of the participants reported ongoing use of prevention medication prescribed as part of typical clinical care, with most participants reporting no medication use at most time points.”

Of 205 teens who participated in the CHAMP study, 80% participated in the follow-up study for two years, and 76% stayed involved for all three years.  Overall, the youths were experiencing an average of 11 headache days per month when they entered the CHAMP study, and just five per month at completion. Three years later, participants reported six headache days per month – even though only one of the 153 remaining participants had continued taking a preventive medication.

“One of the key take-aways for families and physicians from our study it that it appears safe to discontinue long-term, constant medication to prevent migraine attacks,” Powers says.

Instead, prevention can be achieved by focusing on daily regimens including staying hydrated, getting enough sleep, regular exercise and not skipping meals. These regimens, and possibly the addition of CBT techniques, make real impacts, Powers says.

It may also be possible that participating in CHAMP changed the course of the teens’ brain development (a process that continues until about age 25). That’s the intriguing implication from a separate pilot study led by Powers and Robert Coghill, PhD, published in April 2020 in Headache, which reports that teens following CBT exhibited measurable changes in brain structure, as measured by functional MRI.

“The study was relatively small, but 83% of participants showed improvements in headache days and these changes were related to these brain biomarkers,” Powers says.

The pilot study was honored with the 2020 Members’ Choice Award from the American Headache Society. Now, a larger study is planned to further explore these findings, Powers says.

New Option for Treating Migraines

One ongoing value of medications is for controlling acute pain when the headaches start. While physicians can prescribe from an array of medications approved for adults, experts at Cincinnati Children’s say over-the-counter ibuprofen may do the job for most children and teens – if taken at the right dose and at the onset of the headache.

“We prescribe 10 milligrams per kilogram of body weight,” Powers says. “If that dose level fails to reduce the pain within one hour, then we may consider changing acute medications.”

Now, a study published online in December 2020 in Headache reports positive results from teens using a wearable device called Nerivio that delivers “remote electrical neuromodulation” (REN) once a headache starts.

The device is made by the Israel-based company Theranica. Hershey was the study’s principal investigator. Headache Center members Joanne Kacperski, MD, and Marielle Kabbouche Samaha, MD, also were involved in reviewing the protocol and enrolling participants.

Findings from this study helped support U.S. Food and Drug Administration approval in January of Nerivio as a migraine treatment for people aged 12 and up.

The system involves a wearable device for the upper arm controlled by an app that users download to a smartphone. As soon as a user feels the early signs of a migraine attack, they activate the device for 45 minutes, which in turn delivers a mild stimulation signal to skin nerves that in essence interrupts the development and progression of an attack of migraine.

Of 39 participants who used the device, 71% reported pain relief within two hours and 35% reported being pain-free at that point. About 54% also reported disappearance of nausea while 40% reported disappearance of light and noise sensitivity. Only one participant reported feeling a temporary slight pain from the device.

In a subanalysis of these study participants, published June 29, 2021, in Pain Medicine, the device appeared to outperform medications.

At two hours post-treatment, pain freedom was achieved by 37.1% of the participants using REN, vs. 8.6% of participants treated with medications. Pain relief was achieved by 71.4% with REN, vs. 57.1% with medications

“To my knowledge, this is the first study that directly compared remote electrical neuromodulation and standard-care treatment options in adolescents,” Hershey says. “Migraine in adolescents is associated with poorer performance and absence from school and social activities during a particularly formative time in life. Providing teens with more effective and engaging treatments for migraine can have far-reaching positive effects over the course of their lives.”

Multiple patients at Cincinnati Children’s have already started using the device, primarily those going through a four-month wash-out period with no pain medications to treat analgesic overuse.  The device may also be useful for children in school settings who might not be able to quickly get their migraine medications from their school nurse, researchers say.

Cost-Effective Study

Investigators at Cincinnati Children’s report that the three-year CHAMP follow-up study went beyond shedding light on migraine by also demonstrating the effectiveness of using digital technologies to conduct certain studies.

While the initial CHAMP study involved 31 research centers, Cincinnati Children’s alone was able to conduct the follow-up work. Far-flung participants were contacted electronically, completed digital consent forms, and filled out online questionnaires.

“Young people graduate from high school, head off to college, move into apartments. Families relocate. Divorces occur. But we achieved a remarkably high retention rate for this follow-up study,” Powers said.

Importantly, the project cost about $75,000 in support expenses, including the need for approval from only one institutional review board. The required approvals, training and planning time involved in setting up phone banks at 30 other hospitals would likely have cost more than $1 million, Powers estimates.

“Without the approach we used, we might never have been able to conduct the follow-up study,” he says.

Next Steps for Migraine Research

Looking forward, Cincinnati Children’s will be using funds from two NIH grants (valued at a combined $6.15 million) to expand upon the CBT brain biomarker pilot study. Investigators plan to recruit as many as 175 children and teens to be randomly assigned to one of five different arms of the study:

  • A full-scale CBT prevention program
  • A therapy program focused only on the cognitive aspects of CBT
  • A therapy program focused only on relaxation techniques
  • A group that receives amitriptyline
  • And a group that receives placebo pill.

The goal is to differentiate which fMRI brain scan results track to which form of treatment. Having such information could help clinicians direct young people to treatments more likely to work for them.  Results are expected in 2024.

Meanwhile, experts from the Headache Center will continue evaluating an emerging class of migraine medications for potential use in children and teens, including monoclonal antibodies that target the CGRP (calcitonin gene-related peptide) receptor and other medications that directly inhibit CGRP.

“We serve as advisors to nearly all of the companies developing these treatments,” Hershey says. “We are actively enrolling participants for some CGRP studies and will be enrolling for others. We also are working to evaluate these medications in the 5- to 11-year-old age group.”

 

Publication Information

Original Title:Prevalence of Headache Days and Disability 3 Years After Participation in the Childhood and Adolescent Migraine Prevention Medication Trial
Published in:JAMA Network Open
Publish date:July 12, 2021

Read the JAMA Network Open Study

Research By

  • Scott Powers, PhD

    Scott Powers, PhD

    Co-Director, Headache Center at Cincinnati Children's

    My research includes clinical trials in the areas of migraine and headache as well as child behavior and nutrition science.

  • Andrew Hershey, MD, PhD

    Andrew Hershey, MD, PhD

    Director, Division of Neurology and Co-Director, Headache Center at Cincinnati Children's

    My clinical interests lie in improving the outcomes for children, adolescents and young adults with headaches, most of which are migraine. My research seeks to understand the clinical and biological characteristics of headaches.