S3:Ep18 – A Multi-Tiered Treatment Approach for Pediatric Migraine


Voice-over: Welcome to Spotlight on Migraine, The Professional Series, hosted by the Association of Migraine Disorders. Join us as we dive deeper into migraine topics with guests from the medical field. This episode includes educational content intended for medical professionals but may be interesting to some patients as well.

In this episode, Dr. Christopher Oakley shares his multi-tiered approach to treating migraine in children and adolescents, which includes lifestyle modifications, alternative medicines, nutraceuticals, and medication.

This episode is brought to you in part by our generous sponsor, Lilly.

Dr. Christopher Oakley: Hi and welcome. My name’s Chris Oakley, and I have the pleasure of being here today to talk about pediatric migraine treatment. I have no disclosures. There’s no financial disclosures I have. I will say that pretty much all treatments that are discussed will be off-label, as there’s very few things formally approved for the use in migraine and headache treatment in pediatrics.

A few just quick objectives and outlines — we’re going to do a quick case post-pandemic, a very brief overview of pediatric headache, and then we’re going to talk about the treatment of pediatric headache, including the new treatment guidelines that came out in 2019.

Now, pediatric migraine background — just so you know, headache in general is the number one reason for presenting to a primary care provider, an urgent care ER, or for a referral to pediatric neurology. Migraine itself is actually the most diagnosed headache within pediatric neurology and/or a headache clinic specifically. It actually falls under the WHO’s top 10 diseases regarding disability worldwide. And in the US alone, pediatric headache, which most of this is migraine, falls under 200,000-plus missed days of school per year.

When you look at the cost of the disease, you need to keep in mind it’s a costly disease in many senses. So, from a financial standpoint, going back just a couple of years, the cost of headache and migraine was estimated to be near $20 billion in the US alone, and that’s total cost, direct and indirect. When you look just a year or two ago, it was estimated that $20,000 to $25,000 per patient per year was the cost for migraine. And this would also include pediatrics, where it’s missed tuition, missed school, missed parents’ work, as well as all the medical care and treatments that come with that.

It’s costly in other ways too. For many of these kids, their quality of life is actually pretty low. And while we wouldn’t think of migraine and headache on the same playing field as things such as diabetes, arthritis, or cancer, when you look at multiple studies over the years, this is where these kids fall out. Their quality-of-life scores are just as low as those with those conditions. They also found that these kids have a higher rate of behavioral and emotional distress and concerns, as well as multiple mental health concerns, including depression and anxiety.

When you think about treatment, especially an approach in 2020 — and this was prepandemic. This is in early 2020, and, honestly, even at this point postpandemic. But to me it’s a multi-tiered approach. I always use a building-a-house analogy. And no matter what age child I have, whether they’re young or old, whether they’re preschool or whether they are a grad student, they understand that you start with the foundation, you start at the base, and you work your way up. If you try to start building from the roof down, it’s not going to work. 

And that’s why, for the multi-tiered approach, the first tier is always going to be lifestyle. That’s the foundation. Second tier is sort of the structure, the frame, if you will, and that’s the complementary and alternative therapies, the vitamins and supplements. The third tier is the roof, and that’s really the crux of what we’re talking about today, and that’s where we’re talking about medications and treatments that we can provide as the provider, as the doctor or provider. And then the fourth tier is sort of the finishing touches. And, again, we’re not really going to talk about that today, but that would include things like procedures such as nerve blocks or Botox, as well as devices that I will mention briefly.

So when you really look at the foundation, that lifestyle, that first tier, you really have to focus on five or six categories. Sleep is really important. You have to make sure these patients are getting good sleep hygiene and age-appropriate sleep. From a diet standpoint, we focus on consistent, well-balanced meals and trying to minimize or avoid caffeine. 

Hydration is really key. These kids are often dehydrated, as most of us are. It’s amazing when I ask the kids how many times a day do they go to the bathroom, and they’ll say one or two or maybe on a good day three times a day. And they’re proud of it. And they say the bathrooms are dirty and they just don’t have time or whatever the case may be. The parents are shocked, but the reality is parents stopped worrying about how much their kids were drinking once they were potty trained. As long as they weren’t having wet clothes or a wet bed, parents didn’t care. And so we kind of lose track of that. So hydrations is really important.

Exercise, also critical. It’s recommended to have daily exercise; however, reality is most of these kids are too busy with their day-to-day life to do that. So I stress three to four times a week of good cardiovascular exercise for about a half an hour. And then there’s working on that day-to-day stress, that being busy. These kids have a lot going on, and managing that is hard, and recognizing if there’s a problem is critical to making sure their headaches are well controlled.

When you talk about sort of the second tier, now we’re putting up that frame of the house. We’re putting up sort of the supporting walls, if you will, and now we’re getting into the complementary alternative therapies, and these overlap. And what I want to point out is that these are all evidence-based therapies for both pediatrics and adults. Now, there’s more evidence in the adults, but they do have good evidence in even the pediatric cases.

The number one recommended behavioral therapy and/or complementary therapy for pediatrics is cognitive-behavioral-therapy pain counseling. This would also include biofeedback as a top option. Additionally, physical therapy as well as things like acupuncture, craniosacral therapy, and others have been shown to be beneficial and helpful for many of these patients. 

And then there’s quite a few nutraceuticals, such as vitamin B2, magnesium, CoQ10, and melatonin that can be quite helpful. There are others that are out there, but these are the ones that either have more robust evidence or have been shown in pediatrics specifically to be beneficial and the ones that I typically recommend or encourage patients, if they want to go this direction, to take.

Now we finally get to putting that roof on. So we’ve gone through step 1, step 2; now we’re at step 3. You’ve got that foundation. You’ve got that supporting structure. Now you’re getting to the medications and the treatments. So before we really talk about that, I like to show this, even though I know it’s from an adult study a number of years ago. It gets to the point of we often wait too long to start treatment in these kids. 

When you really look at when treatment should be started, anybody in those red categories there on the screen, they should be offered a daily preventative and really should be on one. Anybody in the yellow, you have to consider it. And anybody in the green, they probably don’t need one. 

And what it really comes down to, and what I tell families and kids as well, is if you’re having more than one headache a week that is problematic, you probably ought to be on a treatment. If you’re having two to four a month that cause you to miss activities — school, sports, extracurricular clubs, family outings — you should at least consider it. If you’re having less than two a month, you probably don’t need to be on a daily preventative and you probably aren’t typically being seen by the neurologist or in the headache center.

With that said, this is sort of the recent history of pediatric migraine treatment. Pre-October 2016, all we had to go on was the 2004 guidelines that recommended flunarizine as the only treatment. Now, these guidelines were fairly outdated and from a while ago, but that’s because there was such a paucity of literature and evidence and studies in pediatric headache and migraine, there really wasn’t much to say. That’s really all the guidelines recommended. They did support amitriptyline and topiramate with some evidence and some support, and between 2004 and 2016, these were probably the two most commonly recommended or used drugs for treatment, mainly because that’s what people used to do and they kind of stuck with it.

Then in 2016 the CHAMP study came out, which was a very large NIH-funded study that compared amitriptyline to topiramate to placebo. And it was a multicenter study going on in pediatrics only comparing these three. This study actually was stopped early because it met their endpoint and there was no way, given what the numbers showed, that that would have changed even if they went to full completion. 

What it showed was that there was really no statistical difference whether you used amitriptyline, topiramate, or placebo. What I want to stress and what I think is the most important here, it’s not that nothing works; it’s that everything worked. Even with placebo, these kids reported between a 55 to 75 percent improvement, depending on how you looked at the data and what metric you were using. And that was comparable, almost identical, to amitriptyline and topiramate. 

So it wasn’t that nothing worked; it was that everything worked. And, really, the take-home point is not that we’ll do whatever — everything works; it’s that the structure of how you present this is key. And the key was doing a unified approach, doing a multi-system approach, multi-tiered approach, looking at lifestyle, considering complementary therapies, and picking something that everybody was in agreement with. Getting the kids on board and having them stick with treatment showed during this study and others since then that it really made a difference and it helped getting these kids back on track and getting them feeling better.

A couple of years later, in November of 2018, there was a recommendation report put out by multiple pediatric headache specialists, including myself, across the country looking at the anti-CGRP treatments and the monoclonal antibodies and recommendations, and I’ll be covering those briefly in a few minutes. And then, most recently, there was the new prophylactic guidelines that came out in August of 2019. There’s also acute guidelines that came out at the same time, but I’m not going to focus on those today. 

This was the first update since 2004, and I want to spend just a quick minute talking about these new guidelines. They’re not on the screen here; you can look them up. But, in general, what they said was, number 1, review and modify lifestyle, behavioral, and any risk factors. Back to the basics. Focus on the simple things. Focus on what you can control, and that’s lifestyle. 

Number 2 was consider daily preventatives when headaches are frequent, causing disability, and/or medication overuse is present — again, back to that slide I showed of consider treatment earlier than we used to and talk about it openly because if you wait too long, you get into trouble. You get them into that chronic state or you get them into a refractory state where it’s going to be more challenging to get them out of it.

They did mention, as another point, that you should comment about the CHAMP study and let families know about placebo and medications being similar. Now, I honestly don’t do this. I just let them know that what the evidence shows is that all the treatments, when used appropriately in the right combination and focusing on the foundation up, typically works and that that means that we have a bunch of options available to us. We’re not tied to just one or two.

They went on to comment about making sure with certain medications such as topiramate or valproic acid that you educate and counsel families and kids on the medication side effects and also concerns with pregnancy, should you be working with girls past puberty. They finally talked about screening for depression and anxiety and treat appropriately, that this is often missed or misrepresented and under-respected as far as a cause of the headaches, and if you don’t address it, then there could be problems.

So that’s what the new guidelines say. And then you get into treatment and sort of the COVID pandemic post-March 2020, and we’re going to talk about that a little bit here.

So quickly about the anti-CGRP treatments in pediatrics — going back over a decade, there was evidence and studies showing that in pediatric migraine specifically — not to say that it’s not true in adults — but in pediatric migraines, you also see a marked elevation of CGRP within an acute migraine. So it makes sense that these treatments also would be effective and beneficial for pediatrics. And there are the four that are currently available, and you can see when they came out. You all know these. But they have not been approved for pediatrics. 

Now, clinical trials were under way when the pandemic hit but had to be put on hold, and, hopefully, they’ll be going back up soon as time goes on as the pandemic evolves, changes, and hopefully settles down. That recommendation for the use of anti-CGRP treatments in pediatrics is mentioned there in 2018. And going over that specifically — this is from that article — you can see that in general, they’re considered very safe. 

Now, there’s no specific pediatric studies looking at safety, but when you look at the adult evidence in the adult studies and then anecdotally in small reports within pediatrics, there’s really a very low rate of reported side effects and even lower for serious side effects. The biggest things that are noted are site reactions, which we all know; constipation, and, again, what was reported was about 5 percent or so. We’re seeing about that, maybe a little bit higher, in the real world, just anecdotally. And then what we’re also seeing across the board both in our adolescents and some in our adults, at least what I’m seeing more and more, is some complaints of some joint discomfort, joint pains, arthralgias, even though that’s not something that is typically reported from the studies going back.

The recommendations by the pediatric headache group from that report in 2018 was that if you’ve got more than eight headache, eight migraines a month, you should consider this. If you’ve got a PedMIDAS showing a moderate to severe disability or dysfunction, you should consider this. If you’ve failed two treatments, including nutraceuticals or complementary or alternative therapies, nonpharmacological treatments, you should consider this. And, essentially, if you’re past puberty, just as a precaution, would be another sort of indication when it would be considered.

You shouldn’t use it if you’ve had a CNS infection or neurosurgery, if you’ve got significant cardiovascular disease, history of stroke, or if you’re pregnant or considering being pregnant. And then you would monitor the same things you would with other meds with pediatric patients. You would monitor their pubertal status. You would monitor their growth in all measures. You would monitor for any immune concerns, increased rate of infections. And then you should also monitor for their pregnancy status.

Prophylactic therapy in the real world post-2019 sort of comes as this. It’s still a multi-tiered approach with lifestyle as the foundation. You still have to focus on that, and that’s where you’re talking about sleep, hydration, diet, and exercise. You have to also keep in mind looking at complementary alternative therapies as a great option if available. The recommendations in pediatrics from the guidelines from 2019 included amitriptyline with cognitive behavioral therapy specifically, topiramate, and propranolol. And then I would also argue that with the younger patients and from smaller studies or anecdotal evidence as well that cyproheptadine is often used and a great option, especially in the younger pediatric patients, especially with those with migraine precursors such as cyclic vomiting or abdominal migraine. And then I would also argue that CGRP monoclonal antibodies are a great option if you can get them approved through the insurance companies, given that they are not technically approved in adolescents. That can be a struggle, and you often need to show you’ve tried multiple other treatments, but it can be done, and it does work.

And then other options that you see on the screen there — this is a partial list of all that I use or have used for pediatric headache and migraine. There’s a lot of different options out there. I would also mention that I use devices and technology, and there are several out there, including there’s Cephaly, there’s some new devices with Nerivio, Migra, as well as other things such as GammaCore or the handheld vagus nerve stimulator. Now, some of these are not available or accessible for pediatrics, but some are, such as Cephaly and eNeura.

When you think about where do you go? how do you make that decision? which treatment do you start? you look at the comorbidities. So, for example, I treat the patients as a whole. I look at them as a whole person. So if they’re having migraines as well as sleep issues, I’m going to go with a TCA, cyproheptadine, maybe melatonin. If they’ve got marked anxiety or depression, I might consider a higher-dose TCA or and SNRI or maybe even an SSRI. There’s some debate whether SSRIs is a primary headache medicine or treatment or not, but there has been some benefit with some patients. If they’re overweight or have obesity, I would consider treatment with topiramate or zonisamide. If they have dysautonomia, POTS, consider a beta-blocker as a first-line agent. If they’ve got comorbid seizures or epilepsy, you’d be thinking about one of the AEDs. And then if you’ve got concussion or trauma or post-traumatic headache, consider a TCA.

So, with that said, I hope you got something out of this and picked up at least a little bit about the multi-tiered approach for treatment of pediatric headache and migraine in 2020,e specially with the pandemic, and that hopefully this helped you answer some questions about where we’re going and what we’re working with here in pediatric migraine during the pandemic and hopefully beyond. Thank you for your attention, and I’m open to any questions and comments at this time. Thank you.


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*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.