Evolution of Migraine Treatment Practices

Headache is among the most common neurologic disorders worldwide. The differential diagnosis for primary and secondary headache disorders is broad and making an accurate diagnosis is essential for effective management.

In this episode, Lyell K. Jones Jr, MD, FAAN, speaks with Amy Gelfand, MD, who served as the guest editor of the Continuum® April 2024 Headache issue. They provide a preview of the issue, which publishes on April 3, 2024.

Dr. Jones is the editor-in-chief of Continuum: Lifelong Learning in Neurology® and is a professor of neurology at Mayo Clinic in Rochester, Minnesota.

Dr. Gelfand is an associate professor at Benioff Children’s Hospitals, University of California San Francisco in San Francisco, California.

Additional Resources

Continuum website: ContinuumJournal.com

Subscribe to Continuum and save 15%: continpub.com/Spring2024

More about the American Academy of Neurology: aan.com

Social Media

facebook.com/continuumcme

@ContinuumAAN

Host: @LyellJ

Guest: @aagelfand

Full transcript available here

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, a companion podcast to the journal. Continuum Audio features conversations with the guest editors and authors of Continuum, who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article by clicking on the link in the Show Notes. Subscribers also have access to exclusive audio content not featured on the podcast. As an ad-free journal entirely supported by subscriptions, if you're not already a subscriber, we encourage you to become one. For more information on subscribing, please visit the link in the Show Notes.

Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum Lifelong Learning in Neurology. Today, I'm interviewing Dr Amy Gelfand, who recently served as Continuum's guest editor for our latest issue on headache disorders. Dr. Gelfand is a child neurologist at the University of California, San Francisco, where she is an associate professor of neurology, and she also happens to be Editor-in-Chief of the journal Headache. Dr Gelfand, welcome, and thank you for joining us today.

Dr Gelfand: Thank you so much for having me.

Dr Jones: Dr Gelfand, this issue is full of extremely helpful clinical descriptions and treatment strategies for headache disorders. With your perspective as the editor for this issue - and you've just read all these wonderful articles and edited these articles - what were you most surprised to learn?

Dr Gelfand: I would say that the medication overuse headache article I think is where you'll find the most surprising content. This is an area in headache medicine that has been controversial. I think what we've got is new data - relatively new data, published in Neurology (in the Green Journal) in 2022 - the MOTS trial, showing that what we all thought was not necessarily true. In headache medicine, there was this mantra that, if somebody is overusing (too frequently using) a certain kind of headache acute medication, you've got to stop them; you've got to have them stop it completely before you can get them on a preventive treatment if you expect it to work. Turns out, in this trial, that's not the case. People were randomized to either stopping the overused acute medicine and starting a preventive versus continuing it and starting a new preventive, and they did equally well. I think that's really taught us that that dogma was not based in evidence (was not true), and what really matters is getting a patient started on an effective migraine preventive treatment.

Dr Jones: Wow, that is really – that is kind of ground shaking, isn't it? That's going to change a lot of practices for a lot of neurologists out there. Do you think that's going to be well received, or has it been well received so far?

Dr Gelfand: I think it has. I want it to get out there further, so I hope everybody will read in that chapter and really pick up on that piece. I think it's helpful for patients, too - that we don't necessarily need to disrupt what makes them feel like they're getting some acute, in-the-moment relief. We just need to make sure we're getting a good-quality migraine preventive therapy started. That's the most important thing. We don't necessarily need to ask them to change something about their acute treatment.

Dr Jones: That's fantastic, and it certainly could make things a little more straightforward, I think for people who are helping patients manage this. To be honest with you, the term, “medication overuse” almost sounds like it's putting the onus on the patient a little bit.

Dr Gelfand: It very much does sound that way. It is a very challenging term for a lot of reasons. And I agree with you that that's a problematic part of this whole terminology.

Dr Jones: Well, just three minutes into the interview here and, Dr Gelfand, you've already changed people's practice. I think that's wonderful, and we'll look forward to reading that specific article in the issue. Again, from your view as a headache specialist and a leader in the field, what do you think the biggest debate or controversy is in headache medicine right now?

Dr Gelfand: I think where we're really a little bit stuck in trying to figure out how to move forward is how to take care of patients who have continuous headache. It's not even really a fully defined term, but if you imagine a person who - they wake up, headache is present; it continues to be present throughout the entire day; they go to bed- it's still present; if they happen to wake up in the middle of the night to go to the bathroom, it's there then - it's just there all the time. It can be hard to imagine that situation is real - that somebody could have a headache that is continuously present for weeks, months - but this is true of some of our patients who have chronic migraine, our patients who have new, daily, persistent headache, certain other headache disorders. This entire group of patients who have continuous headache have historically been excluded from treatment trials, so our existing data don't necessarily generalize to how to treat their condition. And we need to change that, because this is a group that is arguably most in need of research, most in need of effective therapies. The question is how? Who exactly should be included in the inclusion criteria? And then, what are your outcome measures? Historically, in migraine treatment trials, we use headache days per month or migraine days per month. Days of headache per month may or may not be the right primary outcome measure for somebody who's starting from a point of continuous headache. Maybe more appropriate is, how many severe headache days you're having in a month, or how much disability you have from your headache disease. It's an area that's evolving and really does need to evolve, because this is a patient population that has been underserved in research thus far.

Dr Jones: I learned that, I think, in reading one of the articles talking about continuous headache at onset – so, the headaches that are continuous from day one, which is, as I understand it, pretty uncommon. But really very little of the clinical trial data speak to how to care for those patients - is that right?

Dr Gelfand: That is exactly right. And, epidemiologically, maybe not as common. But in a headache clinic, we certainly see patients who have had these headache disorders where it starts on one particular day, it becomes continuous within twenty-four hours of onset and has now been going for at least three months, and we would call that new, daily, persistent headache. Or equally commonly, people with chronic migraine where it ramped up over maybe a short to medium-long period to daily and continuous. And now they have been experiencing continuous headache for some number of months, if not longer.

Dr Jones: This question may be a little bit of an unfair question. One of the challenges with headache is that, unlike some other areas of a diverse specialty of neurology, there aren't as many biomarkers as you might have for dealing with patients who have cerebral ischemia or neuromuscular disease. Do you find that that leads to more differences of opinion or more variability in diagnosis and management than you might see in other areas?

Dr Gelfand: I'm so glad you asked that question. What I find that leads to is more stigma. Many of our patients are not believed, including by medical professionals who they've met before. People might think they are faking their symptoms, or that there's some sort of secondary gain, or this is something related to - they just don't know how to manage stress. This is a real problem for patients with migraine to be encountering so much stigma. As a headache medicine clinician, when I'm meeting a patient, oftentimes I need to make sure to acknowledge that, almost certainly, they've encountered that before. I need to reassure them that they're not going to be experiencing that in our headache clinic, and really try to undo some of that harm to be able to build trust that we're going to have a collaborative relationship moving forward - we're going to be a team; we're going to be determining the next steps in treatment together - and that I 100% believe them that the symptoms they are experiencing are real, are very challenging. Because migraine and other primary headache disorders are real neurologic diseases that can be quite severe. But because we have a paucity of biomarkers, it's hard for some people outside the field to recognize that. And that, I think, has been really difficult for patients historically.

Dr Jones: So, a challenge for clinicians has become really more of a burden for patients.

Dr Gelfand: Yes - well said.

Dr Jones: Yeah. That's too bad, and maybe someday that will change, and probably can be approached from a couple of different directions, right? - from educating clinicians’ perspective and also pursuing the science. This might be a related question, Dr Gelfand - what do you think the biggest misconception you've encountered in - I'm thinking mostly from the provider of the clinician community - what do you think the biggest misperception or misconception there is about patients who have headache and the management of those patients?

Dr Gelfand: Well, I think it is tied in, in some way, to this notion that the patients are somehow causing their problem; that it's something about - well, I'm a child neurologist; I see adolescents and children – so, their parent is causing their problem because they're a helicopter mom or whatever it is, or they're just not managing stress in an appropriate way. I think that that is really an issue that patients are sort of handed from the medical community. Whereas if I step back and think about it, before 2018, no migraine-specific preventive therapies existed. We were borrowing from all other corners of medicine. We were borrowing from antihypertensives, antiseizure medicines, antidepressant medicines, but there was no actual migraine-specific therapy. Then came the monoclonal antibodies targeting CGRP (calcitonin gene-related peptide) - they're targeting either the ligand or the receptor. We now also have the oral forms that target the receptor, the gepants. So, we do have this one or two classes, depending on how you break that out, that are migraine-specific preventive therapies. But that's not enough for a complex disease like migraine - we need twenty of them. Look at epilepsy; there are probably twenty-plus antiseizure medicines, and yet, some patients still seize. Is that because they're anxious or stressed, or their mothers are too stressed? No - it's because some people have terrible epilepsy. And yet that same explanation has not been afforded to people with difficult migraine disease, that with just one class of migraine-specific preventive (or two, if you break out the monoclonals and the gepants) - that, somehow, they're supposed to have magically stopped with this treatment. That really doesn't make any sense. It's because we don't have enough effective therapies that they're still having difficult migraine - it's not because they're causing their disease.

Dr Jones: Thank you - that's a great example. That is important to understand - that misconception about causation. And we may come back to causation here in a moment. It really doesn't make any sense that there are few specific, disease-modifying therapies for migraine, which affects tens of millions of people in the United States alone, right? Why is that? Why are there so few?

Dr Gelfand: First of all, Dr Jones, I love it that you called it disease-modifying therapy, because that's how I think about it, too. The term, “preventive migraine therapy,” which is the more commonly used therapy, is not always really useful because - some people who have continuous headache will say, “Well, what are you trying to prevent? I've got headache all the time.” But this is really just treatments that are designed to dampen down disease activity in any form - how frequent, how long of duration, how intense - and I think it is really better conceptualized as disease-modifying therapy, so I love that you use that term. Why have there been so few? I think that it comes down to a paucity of research. Historically, NIH has underfunded migraine and other primary headache disorder research quite a bit, compared to how much disability those diseases cause in Americans each year. Hopefully, that will be getting better soon; I think there are some positive signs that that could be moving in a more positive direction. But I think, because migraine and other primary headache disorders are “invisible” illnesses - can't show you an x-ray with a broken bone; can't show you a lab readout with what your disease activity is; like you said, there's not a lot of biomarkers. Because of that, it's been hard for funders to really get behind it, and I think that's put us a little bit behind where we need to be. More research will lead to more therapies.

Dr Jones: Let's hope so. It certainly is very common and affects, again, millions upon millions of people and leads to impaired quality of life and disability, as you point out. You are also the editor-in-chief of a leading journal in your field, Headache. I know many of our listeners who are neurologists and perhaps interested in editorial work as a career path might be curious - what led you to that, and how has it helped you as a clinician (being in that role)?

Dr Gelfand: Yeah - I love being the editor of Headache. It's the journal of the American Headache Society. I think it's where the most interesting new science and work in headache medicine is coming out of. I have always found that reading helps me learn. If I want to learn about a topic, I need to read about it and I need to synthesize everything I read about. Being an editor makes that so accessible and fun. I really enjoy reading all of the articles that are coming in. It really helps me to think about everything I know, and thought I knew, in the field. And keeps my mind really questioning – do I really know that that's true or did I just think that's true? - and now this new data shows me that, actually, it's something else. And I really enjoy being challenged that way, on a daily basis, by new science that's coming in. So for anybody out there who has an interest in editing and playing an editorial role, I definitely encourage you to pursue that. There are programs - I know that the Green Journal has a resident and fellow section; that's where I started out, and I really had a wonderful experience in that. And then in our journal, in Headache, we have an assistant editor program for junior people - residents, fellows, postdocs - people who want to learn more about how to be an editor. I think that you learn so much about how to be a better writer, how to be a better scientist, how to communicate your findings in the most effective way. It's just invaluable and it's very fun.

Dr Jones: It is kind of selfishly fun, isn't it?

Dr Gelfand: Right, right.

Dr Jones: Yeah, and it's important work, obviously - to put good information out into the world. At Continuum, we also have - on our editorial board, we have two residents and fellow positions, again, for that career development. I have to ask you a really hard question here, Dr Gelfand. You mentioned you read to learn; if you had to make a choice - electronic or print - what would it be?

Dr Gelfand: Electronic. I know that many journals, including ours, are having to make some of these decisions right now. But I read my PDFs and I store them so that I can come back to them and search for them, and make sure, when I'm citing them, that they actually say what I thought they said because sometimes I need to look back at that. So, I am an electronic person. How about you?

Dr Jones: I think I'm print.

Dr Gelfand: Uh huh.

Dr Jones: And I'm just sitting here thinking, there are so many people listening to this interview, and they're screaming at their device, saying, “Electronic is the answer,” or “Print is the answer.” Like you, we want to meet our subscribers where they are, and I think neurologists are very clear in their preferences. Let's just say we'll agree to disagree, and no one is right and no one is wrong – how about that?

Dr Gelfand: Fair enough - I can respect that.

Dr Jones: All right. I have one more question for you. This might sound like a strange question in an interview between two neurologists talking about headache - what can you tell us about chicken farming?

Dr Gelfand: Well, I'd be delighted to tell you about chicken farming. As you know, because they were squawking earlier in our chat, I've got a little flock of chickens in our backyard and they are an absolute joy in my life. One thing I can tell you is that chickens respond to the photo period (how long the daylight is in a year). Now that it's November, it's the time of year when they don't get a lot of light, so they stop laying very much. I find that between Thanksgiving and about Valentine's Day, we actually start to need to buy eggs, which makes me very sad because I love having our egg supply come completely from our chickens. But we want them to rest and so that's what they're doing. Chickens will not lay very much at this time of year. During the summer and the spring and the fall (in the earlier part of the fall), they will lay almost daily, depending on which breed and how old they are. But at this time of year, it's really quiet - really, just one or two a week, I would say, right now.

Dr Jones: It sounds like a fun hobby. Hopefully the chickens don't mind that you're buying chickens in the winter, and they don't feel offended by that or jealous.

Dr. Gelfand: I worry that they do. I try not to show them the grocery bags.

Dr Jones: Well, Dr Gelfand, thank you so much for joining us today, and thank you for such a thorough and fascinating discussion on headache disorders from your unique position as a guest editor for Continuum, I do encourage all of our listeners to check out that issue. It's really full of phenomenal pointers on practice-changing tips and tricks for managing patients who have headache disorders. I'm really grateful for your time today. And thank you for telling me a little bit about chicken farming.

Dr Gelfand: Thank you so much for having me. It was really fun. And thank you for your interest.

Dr Jones: Again, we've been speaking with Dr Amy Gelfand, guest editor for Continuum's most recent issue, on headache. Please check it out and thank you to our listeners for joining today.

Dr. Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practice. Right now, during our Spring Special, all subscriptions are 15% off. Go to Continpub.com/Spring2024, or use the link in the episode notes to learn more and take advantage of this great discount. This offer ends June 30, 2024.