Good Life Project - Top Headache Doc: Migraine Is Not What You Think

Episode Date: August 3, 2026

For decades, migraine was explained to patients as a blood vessel problem: swelling, throbbing, treat it by shrinking things back down. That explanation is mostly a myth, and it may be part of why so many older treatments never worked.Dr. Fred Cohen is medical director of Headache Intervention and an assistant professor of medicine and neurology at the Icahn School of Medicine at Mount Sinai. He's one of the few headache specialists in the country trained in both internal medicine and headache medicine, has over 40 publications in journals including The Lancet and Cephalalgia, and has lived with migraine himself since his teens.In this conversation, you'll explore:Why migraine is a neuroinflammatory condition, not a vascular one, and why some medical schools still teach the outdated versionThe "broken thermostat" phenomenon of chronic sensitization, and how untreated migraine can convince your brain that constant pain is normalWhy only about 30% of people with migraine ever experience aura, and the surprising range of ways it can actually show upThe current treatment landscape, from triptans to CGRP therapies, Botox, neuromodulation devices, and what's coming nextWhy Dr. Cohen calls this the golden age of headache medicine, and what that means if you gave up on treatment years agoIf migraine has ever made you feel like your body was working against you, or like you'd already tried everything, this conversation will change how you see both.You can find Fred at: Website | Instagram | Episode TranscriptNext week, we're sitting down with Marisa Renee Lee to talk about why the tidy stories we tell ourselves about grief and resilience tend to fall apart, and what it actually looks like to build a life around pain instead of waiting to get past it. Be sure to follow Good Life Project wherever you get your podcasts so you don’t miss any upcoming episodes!Check out our sponsors and resources: Visit Our Sponsor Page Hosted on Acast. See acast.com/privacy for more information.

For decades, migraine was explained as a blood vessel problem, swelling, throbbing, treated by shrinking things back down. Turns out, that's mostly a myth. The real explanation is stranger and also a lot more hopeful than the older one ever was. In this conversation, you'll discover why migraine is neuroinflammatory, not vascular, and why some med schools still teach the old version. You learn how your brain can start treating chronic pain as normal, like a broken thermostat convinced a hot room is 72 degrees. We'll talk about why only a fraction of people with migraine ever get aura and how differently it can show up in so many different ways and so many different people. We'll explore what's happening while you sleep that either clears your brain out or leaves it inflamed and why headache medicine may be entering its golden age. We'll talk a lot about cutting-edge treatments as well.

Our guide is one of the few physicians in the country trained in both internal medicine and headache medicine, Dr. Fred Cohn. So excited to share this conversation with you. I'm Jonathan Fields, and this is Good Life Project. And we'll jump right in after the short break. What is the myth that we have been told or learned about migraines that was either never true to start with or is maybe no longer true today? Yeah. So that's a really great place for it because it's still, I would say, a problem if you go today. So first, let me start with the myth and what migraine is still taught us. So migraine, you know, it's actually, there's documentation of migraine since like BC times.

And I think it was Aristotle actually has in like a log or a diary or whatever, him talking about having blinding light in his eyes than a splitting headache, which that sounds. like migraine with ore yeah so it's been around for as long as we've been keeping documentation of things it's not like a uh an occurrence of something new and a writ the first accepted theory was actually earlier in the 20th century by um dr harold wolf was a very famous like forefather of headache medicine that it was a vascular issue you know migraine it's that pulsating pounding thing but then later on towards the turn of the century we know it's not primarily vascular that's the myth. It's not a vascular thing. And they still teach that actually in like some parts of like med school and whatnot that it's a vascular problem. It's a neuroinflammatory condition. That's what

it is. And again, it's complex. I always tell someone if you figure out a migraine, 100% you win the Nobel Prize in Medicine. We understand a good bit what's going on, but there's still more to do. But it being a vascular blood pressure, so there's a myth. The truth is it's more of a nerve. inflammatory condition. I mean, that's interesting, right? Because I'm somebody who is a migraineora. I have lived with migraines from my entire life since my teens. And I remember hearing early in my doctor visits that this was exactly what you're

describing. Like, it's a vascular condition and that a lot of the treatments were designed around that assumption, none of which ever worked for me or helped me in any meaningful way. So you're saying that that was the assumption until not too long ago, but now there a deeper understanding that there's something different going on here. And that's actually a big fine, if you will, migraine education. I still have, I meet trainees, med students, etc. that they are still learning in their schooling in like the year 2026 that it's a vascular condition.

And there's a concern of like, oh, you know, is it, you know, it's a blood pressure thing or something of that. And again, no, like there is a vascular component of it like downstream, but the primary, aspect thing that's going on on my green is this release a soup if you will of these inflammatory neuropeptides that are released and then downstream yes they can have vascular effects obviously pain you have the oar components

like flashing lights the excise weakness all this other stuff but it's the vasculate parts only one small component so do we know at this point what causes that release that leads to all of this inflammation now that's the question because we know what the release is.

So the way of the scribes, we know when a migraine starts what's happening, or most of it, I should say, but the why. That is what we don't know. So there's something called the trigemolivascular system. And there is a switch. What turns that switch on? Is it all genetics? Is it environmental? Is it dietary?

And in my opinion, it's not just one thing. It's a multitude. But anyway, you have migraine. You have something that predisposes you for the switch. that turns on, and then there is a release of all these neuropeptides. Calstin-gulated peptide, CGRP, which there are now treatments that target that. Amelin, VIP, Pay Cap, PCAP, substance PECO, on and on, and all these peptides come out. We also know there's a concept called cortical spreading depression, and what that is, is this

massive release of potassium. Think of if you have a bucket of water. If you start shaking it, the wave gets bigger and bigger. That's what sort of is happening. you see this ever so growing wave of potassium released, and that's also happening. Again, we don't know the why per se, but we know that's happening, and what that does is it, now in your brain, there's no pain receptors. If I was the melt in the middle of your brain, you wouldn't necessarily feel it. But what happens is the Dura, which is the outside component of our head and brain, that becomes supersensitized.

And we believe it's a pulsating pain because the areas where the blood vessels are going through, that is now sensitized, and that's why I can feel pulsating. The blood vessels is fine, but the area around it is sensitized. And I also, going on myth, you know, you brought that up. Everyone commonly thinks a migraine has to be one-sided behind the eye. No, it could be anywhere in the head. Now, one-sided behind the eye is the most common, but I have people who come thinking they have a neck issue or back in the head pain, and I go,

nah, it fits the migraine, you know, criteria. So really, it could be anywhere in the head. It's not just focused behind the eye. How do we distinguish between a, quote, everyday headache or a tension headache and my way? Or we hear this other term sometimes, cluster. Like, what are the difference between those things? And how do we actually tell? So there are three primary headaches.

And you name them also, tension, which I call, if you will, the regular headache, very broad. It's a mild to moderate pain. Okay. Then you also run up cluster. Cluster is a very specific kind of headache. It's sudden, immediate. That one has to be behind the eye. one-sided, super severe pain for 15 minutes to three hours, and then migraine.

So the way we come to a diagnosis is the sort of clinical picture of the pain. Some of the most important things is duration and the quality. A migraine must be, and I want to stress that this is not black and white, you know, pain is subjective. It's not like, you know, so I have an internal medicine background before I went to headache medicine. You know, when you diagnose a heart attack, you see it. you know, you get a chest x-ray. We can't do that with headache medicine. It's all by feel and pain is subjective. So to those listening, I want to stress, this is not completely black and white.

You know, this is a discussion with your provider. So the pain generally has to be at least four hours. So when someone says, oh, it's only last 30 minutes, I'm not as inclined for a migraine. And it needs to be moderate to severe. And usually the way I find that is it impedes you. You have trouble folks and you've got to leave work. You can't keep going about your day. It's bothering you. versus a tension headache more mild. Yeah, it bothers, you know, but like you could persevere. You're not, you don't have to stop working. And lastly, that it also can be usually pulsating throbby, but again, it doesn't have to be.

But really that duration and the quality is what hones me in. Now, again, we don't have a test to prove this. And it's actually a big popular area of research. but usually these are conditions of exclusions. We make sure it's not something else. You know, if you have certain concerning signs, we may get an MRI, you know, make sure that's fine. Or if there's, you know, a reason to get a blood test, something like that.

But again, there's no blood test to prove it. It's really by clinical picture. So it sounds like those three that you just described, probably the most clearly discerned one is cluster. It comes on really fast and incredibly, intense. Cluster's one that usually, like, yeah, there's no confusion about it because it's so specific and so unique than the others.

I'll give an example, like, it's a severe pain. So typically, you know, the way I bring me up is like, if a patient tells me, I think I'm in Cluster, I'm like, how is it? Yeah, okay. I don't want to come off like, I don't believe the patient, but speak to someone with Cluster, they're like, they're on the ground, they can't talk. Like, so, and again, not like, not the same. sound dramatic, but it has, you know, sometimes it could do this. It has a nickname of the suicide

headache. Right. Because people, you know, it's so severe that it has historically brought people to that, you know, when they haven't got out of good treatment. So it's a very different picture than tension and migraine, which could those have a lot more overlap. Yeah. I guess maybe there's a little confused and just in popular understanding because of the name, because in the name itself, It kind of makes it sound like, well, if I have a headache four days in a row, that sounds like a cluster to me. Whereas like, so the common understanding of that word is very different than the medical understanding of the name. And yeah, it gets, I understand the nomenclature of the term. A lot of patients go, yeah, but it's happening in clusters.

Sure, migraine can do that. Yeah. My people could, you know, it's very common women can have only migraine attacks around their mental cycle. That's a, that is a very common thing. and I've had patients come, oh, I have cluster because they're happening in this grouping. And again, migraine attacks and happen in groupings. Cluster, again, it has to have that specific severe pain. Let's zoom the lens out just for a minute because I'm curious, too, about the prevalence of this,

just across large numbers of people. What are some of the general numbers, like the big picture numbers and stats? For migraine? Yeah, for migraine. Sure. So migraine, you know, our epidemiology suggests it affects anywhere from 40, 60 million Americans. So that's one out of six Americans. More common in women.

So about 18% of American women, 6% American men. So about one out of five, almost American women. So very, very common. Now, chronic migraine, which were those who are having eight or more migraine attacks a month and 15 total headache days, we think that's around 1% of the population. So, you know, not as much as migraine, but that's still quite a bit. And think of having that many migraine attacks and mud, that could be pretty, you know, disabling. Yeah.

And you just described. And I've heard this mentioned also in the past that there seems to be a much higher prevalence in women than in men. Yep. Do we know what that's about? So there's some suggestions. the most, what the most common one believed is we know estrogen is related to migraine attacks. And it's not the level, it's fluctuation. Because I've had patients ask, should I take an estrogen replacement?

I go, hold on, no, that might not solve this. Most women notice their first migraine attack if they get one around their first mental cycle. We noticed that in the first trimester of pregnancy, there's increased frequency of migraine attacks. And for a lot of women, when they go through menopause, there's a lot of women, when they go through menopause, There's no more migraine. That was the case for my mother and my grandmother. Which my mom, when I complain about my migraine, just goes, oh, yeah, way to you get older. I'm like, well, unless there's a phenomenon, I'm not going through menopause.

The other fact that I've heard, which is more gender-specific, is that, and I don't know how you measure this. I'm curious whether there's data on this, is that not only is it more common in women, but that it can also be more painful, more intense. Is that true, or is there data around that? I don't know if there's data really behind it again. It's really hard to quantify pain. Yeah. Because so we have battles, if you will, for migraine in both sexes. You know, there's unfortunately a lot of women's health issues, you know, don't get as higher focus as they deserve and need to be.

So there's always this fighting stigma around migraine and raising awareness of migraine. But on the other side of the aisle that migraine is a woman's disease. And again, where there are many men who have met patients of mine who just dealt with it, thinking it's headache, and didn't see treatment just, oh, I don't have migraine. I'm not a woman. And again, no, like, well, yes, it's more common in women. Sure, men can still get it. And a good amount of men get it.

So, you know, that's actually been a reasoning to shed light that, hey, you're a male having, you know, a headache attack, to speak with your doctor, that could be migraine. as far as which gender has more pain, you know, I, there's no data behind that. And I never like to compare, I tell my page, just never compare your headache or pain with someone else. It's because pain is subjected. You know, how someone expresses pain differs by person, by culture, by so many factors. So that's why I never like comparing. Oh, that's more painful than this, et cetera.

But that's also why in my patient interactions, I don't just ask about pain. I think the best indicator for the impact of someone's migraine a headache is asking about their function. How many days have you missed work in the past month? How many days have you not been able to do like an activity? Go out, spend time with friends. How many days could you not interact with your child? How many days are you taking medication, etc.? Those could go like for someone who I've had patients, especially, you know, being in New York City,

I have a good deal of immigrant patients. They come from areas that don't really have health care infrastructure. so they're not used to discussing or bringing these up with a doctor. And they come because their family member brings them. And they're like, yeah, I don't really have pain. But they usually are asking the questions. How many days have you not been asked for your doctor about work? Oh, yeah, like two or three or three headache attacks a week.

So that's why I don't always focus on the pain number, but these other metrics as well. Yeah, it's such a good point. You know, and I have had in my own experience over many, many, many years. There have been windows where the headaches are so free. frequent, that you kind of forget what it's like to move through the day without them. And it almost becomes normalized where it actually really does become hard to understand. Like, if you were going to rate the pain, it's kind of hard to do that because you're comparing it to sometimes a window that is hard to almost relate back to.

But if you said, like, how is this affecting you? You know, like, is it stopping you from doing X, Y, or Z? A patient of mine who had headaches every day for years. and when I first met this individual, he told me that his headaches were a 9 out of 10. We've done a lot of treatment. They're still daily, but they're down to a 5 out of 10. So I ask him,

would you like to keep trying new therapies? He goes, listen, this pain came out for 9 to a 5. 5 is nothing. I don't want new meds. I'm content. And I said, that's up to you. That's fine. So, yeah, those are just,

they're just numbers. One of the biggest lessons in medicine is treat the patient, not the number. And again, like, yes, I always ask those things, but those numbers are not just specific finite, all right. Like, that's all I'm going to work with. No. Yeah.

You know, one of the most important things is the history. Remember, you know, it's not just looking at, you know, tests and labs on that, but how the patient is presenting it themselves. Now, that makes a lot of sense. And we'll be right back after a word from our sponsors. Hey, so we'd love to share more Midlife Reinvention stories on the podcast. like the recent one from Saribotten, who after decades in her career then being pushed out as she neared 60, launched Oldster Magazine to an incredible reception that even led to a book deal.

We love inspiring stories that show how changes not only possible, but often incredible at any age. And it's not just about work. It's about relationships, location, health, and more. So if you've got a reinvention story you'd love to share, just tap on the link in the show notes and give us a quick summary. and who knows, you might just end up on the podcast. Excited to be inspired by your stories. You mentioned earlier in a conversation that you started out in internal medicine,

switched over to headache. This is not just your practice. This is personal for you as well. Oh, yeah. So I always say never trust a headache doctor who doesn't get headaches. Because, you know, there's a lot of them. So my path was I always had a weekly severe headache since I could remember. It was never thought to be a thing, you know, and this is no complaint.

I'm very close to love my parents very much, although I do give a little bit of stick to my mom, my aunt and my grandmother who have migraine. And never thought that, oh, maybe Fred's having that. So I tell him that, that's the only mistake you ever made raising me. But I just dealt with it all the way until a residency. One day a week, pain out of commission. Now, in residency, you're not sleeping. You know, you're working 80, 90 hours a week.

So now the migraine ramped up. And, you know, I take it as a blessing that I trained at Montefiour, a hospital system in the Bronx, that has a very well-known headache center. And I actually got a lecture from one of their providers. And at the end, I said, hey, I think I got that. And she was like, come on down. I went to see them, had a visit. Life-changing, completely. Now these migraines that took a day a week became non-problematic.

It's not common for me to lose a day now to the migraine. and I learned from them this is a field. And I said, this is what I want to do. This is the field of medicine I want to pursue. And then I learned that headache medicine is a ward certification you don't have to be a neurologist for. You know, you could be an internist, family medicine, pediatrics, OB. Now, most headache medicine specialists are neurologists, the vast majority. We, so I'm like sort of this uncommon one.

But it's also what I love about our field, the collaborative nature. A couple days ago, I just came back from the annual scientific meaning of the American Headache Society, and you meet people of just not from different areas, but different backgrounds, physical therapists, occupational therapists, psychologists, you know, of course, internists, family medicine, peeds, et cetera. And, you know, it's such an interesting field that most fields of medicine are just in their own, you know, their area, whereas this, it's different specialties coming together. I mean, that makes a lot of sense to me.

And also, it sounds like, tell me if this is accurate or not, as you described, you know, there's neuroinflammation. There's inflammation in the brain. It, part of the theory is that it somehow affects the dora. And that's where a lot of the actual receptors are, which we translate to, oh, this is painful. But I would imagine also, like, that it's systemic. Like, this is not something which is, you know, like, reserved to what happens from the neck up. there's something going on that's more broadly systemic that also influences the entire experience. It affects other systems.

So, for instance, the GI tract is involved. We know during a migraine attack, there is gachshopresis. Gashopresis is, you know, going with the line and term, not per se paralysis of the gastric system. So the stomach isn't moving as much. This is why we think there's nausea. There have been studies called a barium swallow. patients drink a, drink a dye, and we can see it on x-ray. And it is confirmed in migraine attacks there is a degree of gastroporesis.

You know, and we know this also. Migrate is not just a headache. There's multiple phases. The prodrome, so the beginning, can have excessive hunger, fatigue, thirst, irritability. Then we have the headache, or the aura phase, then the headache phase. The postdrome is nicknamed the migraine. his nickname the migraine hangover because it's immense fatigue. But yes, it does affect other systems.

Yes, neuro is the most affected systems. And it also is known for having very common comorbidities, anxiety, depression. We know that asthma is a common, you know, comorbid condition, obesity. There's so many things that are involved with it that it's not just neuro involved. It does affect other systems in more than one way. So now I'm curious about two things you just said there, too. One, the early part of it. What was the language you used for sort of like the very early things?

Projome, right? You mentioned, and you mentioned a couple of times this notion of an aura. And that I think is one of the things that in popular lore is associated with like, oh, there's a migraine coming. And for some people, that's true. But that's not true for everyone, right? Ready for me to spill another myth? Yeah. What if I told you that most,

people with migraine don't get aura. Okay. And we think of migraine or aura. No, only 30% of those with migraine get aura. The majority don't. So that's why when someone's like, I don't get aura, I'm like, okay. Like, okay, you don't need to. And you don't need to have an aura every attack.

So aura can be any, I describe it as this, it's any neurological symptom that essentially could last anywhere from 15 to 60 minutes. That timing is very important. Now, some oras can, but an aura should not last long in 60 minutes. If it is, you have to speak to your provider that has to be evaluated. The most common aura is the visual ones. Zigzag flashing lights, blind spot that grows. Some people describe it as kaleidoscope vision.

And generally, there's no pain during it. It happens, it goes, and then the pain begins. But aura could present in a lot of other ways. Or it could present as numbness. It can present as weakness. There are some who have what's called hemiplegic migraine where it mimics a stroke. Some who have vestibular migraine

giving vertical-like symptoms. There are those who have difficulty speaking. There's a famous video on YouTube of a news reporter who's on-camera giving a report and then she starts saying nonsense like jipperish. And they thought she had a stroke. They took her to the hospital. It's migraine.

Now, these have to be assessed to make sure it's not those things. But my point is, migrant aura is not just the visual symptoms, it really will be any neurological presentation. Yeah, I mean, that's so helpful because I had heard that this is much more common than you're describing, but also understanding that aura is not just the classic, you know,

spotty vision or shift in what you see, but it can show up in so many different ways in your body. It really can. Yeah, I mean, that... Those who, you know, lose sense of smell, those get... I want that, they get tinglingness on their tongue for 30 minutes. It really...

What I care about is the duration. That's the key thing. Yeah. That it's last, it's because that is like the one I would say, per se absolute. When someone's like it lasts an hour and a half, we need to get neurological testing to make sure that's not that.

Now it comes back normal. Cool. We'll say it's that that's your aura. Got it. But I really could present in any way it wants. So my other question was about the sort of like the post phase. And you mentioned that fatigue can be one of the things that we feel. That's certainly something that I have felt.

And I've always been curious. about that because it's not just like my head is really tired of my eyes are tired which often they are but my whole body feels like I would just like went through this intense you know like maybe like it just did a 10-mile like that's why we called the hangover it's like when you had too much to drink what's going on there why why is a fatigue our thought why and you know we don't have 100% you know what this is but we talked about a migraine when it's happening, all these neuropeptides are firing, right? What happens if you're running for a while? You push your body and you get tired.

And I like to think of it like that. You have all your brain. It's just neuropeptides are fuel. And when you, you know, just like when you're running a lot, it makes, you know, the engine we're down. And it's that sort of, that's how I sort of, you know, that's how I sort of, you know, you know, visualize in the way that your brain just spent so much fuel and it's like recovering. Let's switch gears a little bit and talk about what we do.

So somebody's joining us and they've had headaches. Maybe they're new. Maybe they've had them on and off for a long time. They weren't sure. Are these tension headaches? Are these migraine? Are they cluster? Maybe now through this conversation, they've got a lot more clarity and they're pretty

convinced they have migraine. And as always, we make clear, like, this is not medical advice. Like, see your qualified health care provider. But I want to zoom the lens out and just explore options that probably a lot of people haven't known about. Let's start with this distinction between prevention and sort of like immediate treatment, intervention and prevention, because it seems like those are two different things, maybe with some overlap.

So if you feel like something's coming on or you're in the middle of the same, something. What are the common available sort of main mechanisms that you look to now to try and stop in its tracks as much as we can? Sure. So I should make one point because this is sort of another myth. Yeah. If you're not, if you don't have a neurologist, start with your primary care. You'll be surprised because a lot of people wait to see a neurologist. You might need to see a neurologist, but if, you know, if someone's having tension of migraine, PCP is the place to start. So, you know, you said it correct. We have acute. preventive. So there's two different

schools of thought of when starting a treatment. Everyone needs acute and a migrant attack happens, but does everyone need prevention? And that's a bit of a gray area. So these are guidelines set forth by the American Headed Society. There's no 100% like this is the where you start. It's sort of a

scale, if you will. Anywhere from at least four to six or more, had to get migraine attacks a month. But also how much the burden is. For instance, if someone tells me they have four attacks a month, but they're not that burden from it, I might just do rescue medication.

So it has three attacks a month, but also they're really impactful. The day after the hangover is really bad. You know what? Okay. Let me start preventative therapy. So that's generally how we pick it. So starting with acute therapy, there are two really common treatments, classes, a triptan family and a G-Pan family.

The triptan family has been around since, I believe, the early 90s. You might have heard of these as Sumer Triptan, Rizant, Tritin, et cetera. There are seven flavors of triptan. They all have their differences, of course. They're available as oral, intranasal, even injection. And they work actually on this 5HT serotonergic receptor. And that actually causes visual constriction. But wait, Dr. Cohen, you said migraines, not a vascular problem.

No, no, we'll get. So, yes, the drug itself does cause videos of constriction, but that causes a decrease in release of CGRP, Capsin-Germal-related peptide, which is a neuropeptide we know in the migraine cycle. That's how it achieves it. Then there's the G-PAN class. You might have heard of these as Remigipant, NerdTech, Ubrojipat, Ubris, V, Zavisap, Zabstrat, and those are antagonists of CGRP,

so they're targeting directly. There's other therapies as well, but those are the two typically first-line therapies I go to for acute treatment. How effective are these? And are they universally effective for everyone? Is it completely different for everyone? I wouldn't call any migraine treatment universal. If there was, well, we hear it.

But these are first line, and they usually are quite effective. I would say, you know, more than often I don't need to go to a different class, that those two classes take care of those two classes take care of. the job. Now, I want to stress if you're someone who those two classes of the whole, that doesn't mean there's anything wrong with you. Again, everyone's migraines unique, but those generally are pretty effective. So let's talk about the triptons for a minute because I think that was sort of like the earlier class of drugs and then the things which are, use a different word. I've commonly heard of them described as anti-CGRP meds. That's a newer class of drug. G-PANs or anti-CGRP meds.

Yeah, G-Pens, right? That's a newer class than the Triptons, right? G-Pent to release at the end of 2020. Okay, so fairly new. That's, you know, like six years old at this point is we're having this conversation. And it sounds like what we know now, and tell me if this is right,

is that the triptons work by a secondary effect in tamping down or limiting CGRP, whereas the newer class goes directly there. But at the end of the day, it's sort of like a similar mechanism. Is that right? So, yes, it's not as concise as that because, well, yes, triptains, in my view, are this sort of secondary effect. They also work quicker.

You know, the mechanism of G-PANCH, what we see is they, on average, take a bit longer to get their effect than the triptans do. So I don't like, like, I get at all time which one's better. Unless, until we do a superiority test, there aren't. You know, I never like to put a claim in which. which ones better. They have their uses. You know, there are some, you know, it's the individual patient if I pick, if they're getting a G-Pan, a triptan first. Yes, in theory, triptan's having a secondary effect, but that's a common thing in medicine. In a lot of conditions, we don't always

get something that goes right to the area of concern that it takes a bit of other things to get there. So I never like to sort of diminish that of its thing. But yeah, triptan's on average, have a quicker onset. So about how long is the difference between those two classes? No, I want to stress this is averages and anecdotally. This is anecdotally. Right. You know, meaning I like I don't want, you know, this is not

you know, clinical trial, whatever. What I see is triptains are anywhere from 30 minutes to an hour per se. G pants are an hour to two hours. But that is my anecdotal answer. I have patients that G pants work very quickly. it all depends on the individual. There's a lot of things going on in the body that sort of dictates that. Yeah.

Does it also depend to a certain extent on the delivery mechanism? You mentioned oral nasal and injection. Yeah, definitely. So we have oral, intranasal, and injections. Generally, injection is the fastest, so suitoritin injectable. We also have suorotryptin and zolmatryptin intranasel and intranasal zavagepan. It's a vaguelytapans. And yes, that one is a quicker onset than the,

oral gpans. Got it. Now, nasal, again, there's, there's no right or wrong for each individual person. I'll give you an example. I personally love intranasal.

What, you know, I use myself. They got a nasty taste. It's not fun getting something, you know, spriturus, but again,

to each their own, they're all useful things. Yeah. So there's not like, I don't just, you know, Sumitripped and injectable is the highest,

the fastest onset. I don't prescribe it to everyone. It doesn't mean that's the, that's it. That's it. That's the one for you. there's different reasons why one would get a certain route. And we'll be right back after a word from our sponsors.

So what about this idea also of medication rebounds? Like I've heard that with certain types of medication, let's say you have a migraine for one day and you take it, migraine for second day. And then I've heard, well, don't take it for the third day because then you have a likelihood of having a rebound. What's true and what's not true with this? So medication adapted headache or medication overuse headache.

They're interchangeable terms. I just gave a talk at the American Headix signing meeting last week on this specifically. So yes. I guess let me first define what is a medicationalicious of use headache. It is using a certain rescue medication. In this case, triptans, opiates, or combination drugs that you're excedrin, more than 10 times a month. Or over the counter, Advil. Tylenol, et cetera, more than 15 times a month.

Over three months. Meaning, if you have one week of taking Aval every day, that's not necessarily going to give you a rebound headache. This takes time. And it's averages. For example, I face it says, oh, I use the tript in three times for three days in a row. Am I screwed? And I go, well, how I'm using it before that?

Oh, once a week. Okay. You know, that short span is not going to do it. It takes time. It takes, it's a repeating. pattern. That's why like when I meet with a patient, let's say, for three months, I'm looking at their overall use, not one week. It's not like if you take a trip to hand three or four times in just one week, that's it. It's all over. No, it takes time for this because what's happening

in a medication overuse headache is your body is, you know, we have a couple of theories that it's going to use a sensitization, if you will. And the brain doesn't go through that so quickly, it takes time. But that's why whenever I prescribe these things, and when I have follow-ups, I always ask about use because we want to prevent that from happening. Let's move on to prevention. What are the main things that we look at here? And actually, what is prevention? Let's define that a little bit more. So great. Think about what we were talking about medication, old use headache, right? Well, if you're having 8, 10, 12, 15, et cetera, heading days a month, can't use a rescue man every day, right? So that's where prevention comes in, reduces the frequency.

I never like setting the goal as curative. I think that's misleading. Migraine typically isn't per se curative breakthrough attacks will happen. I think it's a very important distinction to not be misleading to someone. That's why I always prescribe acute medications, because it will still happen. So prevention is to do that, prevent the migrant attack for happening. And there's now a lot of medications. So I'll do it, I guess, in a chronological order. We have what we call the legacy drugs, which have been around for decades. The three legacy drugs are anti-seizure drugs, to PURAMATE, beta blockers, such as propanolol, and tricyclic antidepressants just as amatryptly and nortyptoly. Their evidence is great, but their original design was for something else,

and also found to be effective for treating migraine. Then, in the late 2010s, we had the first use, first FDA-approved use, I should say, I've CGRP-based medications, the CGRAPO monoclonal antibodies, which is arrangumab, copanizumab, Fremonizumab, and Eptanismab. These are monoclonid antibodies, which are once a month injections, you know, think of it like, you know, a lot of people who live with like, oh, Zempeger Zepbaum, like that kind of applicator, but for your migraine, or once over three months infusions. And there's also a tootropan, eulipter, which is take it back to that neurotechubrovy, right? The G-PAT, you could take it every day.

And that's for prevention instead of acute. We also have Botox. Botox, believe it or not, is FDA-approved for chronic migraine. Meaning, this isn't for everyone. This is for someone who's having 15 headache days a month, eight of which are migraine attacks. And it's 155, the 200 units of Botox injected over the entire head. once every three months.

So, and those are, you know, first lines, then there's a lot of other possible treatments. Again, what goes to me choosing what a patient gets is not only their headache frequency, their comorbidities, and what else is going on in their life. Yeah. How does, I mean, you sort of describe the mechanism for some of the earlier ones. How does Botox actually work in this particular context? So Botox, and you know what, I'll give a good, demonstration here. Botox is given. 31 to 40 injections are on the head. So both by the brow,

the forehead, the side of the head, the occipitalis back of the head, upper part of the neck, and trapezius. And that is how it's given every three months. And the mechanism is anabotrata toxinate, which is what Botox is. When it's injected, it gets into the neuromuscular junction. And what that's doing is preventing the release of neuropeptides at that level. So for cosmetic purposes, because of that, muscles don't move as much. But for pain for migraine, it interferes with the release of neuropeptides related to migraine like CGRP. Which is why I'm actually, and I'm biased, but I'm a big fan for those who have refractory migraine of one of the seizure-p drugs, either the monoclonid antibodies or a cheap hand with Botox.

That was one of the first migraine projects I ever did. Back when I was at Montefiore, we had the first paper showing that together it has a synergistic effect than just by itself are reducing monthly migraine days. Now again, I want to stress that there's, I never like coming off as, oh, there's one great treatment or that's the best treatment. There's many treatments. You know, everyone's saying it is unique because I've had people come up and saying I want A, I want B.

And I'm like, let's talk. And then I'm like, hey, I think C is actually a better fit. So, you know, there's no one true treatment for them all. So what I'm hearing really is that even on the prevention side, there are a range of different treatments. It's really important that you work with somebody who is skilled at understanding what is the best approach for you. And also what I'm hearing you say is that sometimes it's not a matter of just working with one, but sometimes you may weave different things to. together for the optimal effect.

Is that right? There's a lot. There's, I can keep going. There are sort of antidepressants, the S-NRIs, the Loxetine and effects her, have evidence. Blood pressure medication like Candacellarine, a lacynipril have evidence. You have neuromodulation, which is becoming a popular thing, which are these devices you wear, like Cephly goes on your forehead, gamma cores on the neck, Nribio is on the shoulders, Savdies, you know, back of that.

And they work by sort of, it feels like a, vibration, but they're altering your pain pathways, and therefore you're not taking a med. There's so many different treatments, is of course, off-level uses. For patients who are really, really refractory, believe it or not, ketamine. Now, that's very uncommon, but there are some people who warrant that level therapy and have them very well. Yeah, define refractory for me just like what's the common term? Sure. Refractory, I use the same definition.

that the European Headache Federation uses, which is a headache that has become not responsive to at least three or more treatments on average in the span of three months. Class of drugs that you mentioned earlier that I'm curious whether they play any role in this. GLP 1 agonis. Sure. This is actually a really popular thing that was actually discussed also at this past American Edicts'Cxiting meeting. So the GLP 1 agonist, these are your OZempics.

These are your, you know, Ogovi, Zep bound, mandrinos, et cetera. It was seen in those trials that those who had headaches or migraine started reporting less. And anecdotally, a lot of providers saw it too. So the question is how? Is it, and it goes to, is it direct or is it indirect? Because, for instance, we know with migraine or chronic migrate, obesity is a very important risk factor and worsening things. and the reason that we think the GOP1s work at us, of course, it's reducing weight. So is it that it's making headaches better because we're reducing weight or is it having a neuroprotective capability?

There's a proposed mechanism that GOP1s actually get helped reduce cerebral spinal fluid pressure. So our brains are like a goldfish in a tank, this cerebral spinal fluid, you know, increased pressure, intercranial hypertension, IAHs, is too much pressure in the head and that's lead to headache, etc. So it's a question of, is the GOV-1 actually reducing it directly? Is that the mechanism?

Is it suppressing CGRP and some mediated pathway down the road? Or is it just as simple as you reduce obesity and therefore we know. So obesity is an auto is an inflammatory state. Aipose tissue, we know when there's excess adipose tissue, that releases inflammatory markers. So is it just as simple as, hey, there's less weight, there's less adipose tissue, therefore there's less of an inflamed state. So then what's my take on it?

What do I use? Have I prescribed GP1s? Absolutely. But I view it as, do you warrant weight loss? Because I don't prescribe it specifically for only migraine in mind because, again, it will, you know, GP1s will have an effect on weight. that's what they're designed to do. If someone comes to me who has a BMI of, you know, they're not obese, they're 28 or 27 or less, then I don't really recommend it because it might have other consequences.

You know, I wouldn't call this as a wonder pill. They're very popular and have a tremendous effect on bringing weight down and helping resolve obesity. But that doesn't mean that non-obese people should be taking it. You know, like, because there are known side effects. there's a talk about are they causing hair loss, you know, affecting endocrine issues. There's a lot of safety data like I'm always reading about. So I don't directly prescribe it to treat migraine. I prescribe it to those who have those risk factors, diabetes, obesity, et cetera,

with the thought of mind, hey, this will also hopefully help your migraine. And that kind of brings us to lifestyle also, you know, because, yes, so here are a whole bunch of, like medical interventions of, you know, pharmaceutical. interventions to a certain extent. Or you brought up, you know, this growing field of tech and devices, which work in a variety of different ways interrupting pain pathways, stimulates the vagus nerve. And I think we're really early days from what I've seen in that. But when we bring it just down to basic lifestyle modification, do the basics work like nutrition, you know, like exercise, sleep, hydration? Do they make meaningful difference?

Because I don't want to ever come up like, oh, yeah, well, the biggest, stigma in migraine. If I had a nickel, every time someone said, have you tried drinking more water? Like, it's not, you know, it is a neurological condition that, you know, it's not just a lifestyle issue, but it goes, there's definitely a component of it. Because what I was saying before, migraine is an inflammatory condition. Treatments involve reducing inflammation. So proper hydration, proper meals, you know, maybe foods having an effect. So everyone's body reacts differently to different foods. So, you know, when I meet with a patient, the most important. So headache diaries are paramount because that allows me to track data. I tell patients,

don't worry what's in a headache diary. That's my job to be worried about it. And that's when I can start finding things that may be interfering on a lifestyle level. I have found patient inserted foods affecting it. I have a patient. Her eggs could trigger migraines and other those spicy foods. It's not common. Why does it happen to them? I don't know, but that's how their body is responding to that information. There's no one true migraine diet, but I've had patients who have, you know, improved headache frequency, gluten-free, ketogenic, et cetera. And again, it's not because, oh, yeah, that's it.

And I don't want to ever say that's one word for you, but from themselves, they found that that's effective. Sleep is probably the most important thing. I can't stress that enough. When we sleep, when we hit REM, stage four, what happens is our brain activates what's called the glymphatic system. So, don't ask me why it's called that. We have lymphatic.

Okay, when we sleep, add the G. I don't know. So we have the glymphatic system. And remember what's on before with like that migraine hangover and because all those neuropeptides, well, the glyphatic system cleans up the waste of the neuropeptides. That's why when you don't sleep well, you, what's groggy? That's what groggy is. Your brain didn't get to clean itself. So it's inflamed.

It's in this tired state. So if you don't achieve proper stage four sleep, your brain is not cleansing itself and it's in a pro-inflammatory state of mind. And that's why it's every single new patient visit I do. I do a sleep assessment. For those who I think there's obstructive sleep apnea, I'm getting them a sleep test. I diagnose delayed sleep rhythm, insomnia. But sleep is so important. Caffeine gets asked all the time.

Caffeine is a double-edged sword for most people that helps. For some, it makes it worse. I drink coffee myself. Caffeine is fine in moderation. Don't exceed three or four cups a day. You know, sort of a no-brainer with tobacco. Tobacco is known to cause migraine attacks. You know that some of the big, one of the biggest risk factors for cluster headache is tobacco.

Alcohol is a really common treatment for migraine and cluster headaches. Some people make it better. For me, like I abstain from alcohol. It will give me no matter what, you know, that's actually my trigger. But speaking of triggers, you don't necessarily have to have triggers because people get sort of and rightfully so sensitive about it because then when you start talking about triggers, it means you did this, you triggered it. Some things in life are unavoidable.

Like weather. Weather is a very common trigger. And people, I have patients who feel like their doctors call them crazy for thinking that you talked about lightning before. Yes, we like, that's actually a working group I'm part of where we looked at clinical trial data

that at the same time, weather metrics were taken, where we have spoken at headache conferences that we found that if there's a 10 degree Fahrenheit change within 24 hours, you have an increased risk of headache. Same thing, if there's a point two for a barometric change

in 24 hours, You have increases of headache. Headache change is real. No, you're not crazy. So some triggers are just unavoidable. What do you do then? That's where acute medication comes in. Right.

There's going to be a storm happening. You have your trip to any of your jeament or whatever on you. So if it happens, you take that. And that's sort of why I don't like getting too lost in weeds or triggers because some is just, that's the world. Some is just the environment that, you know, the horse can move a lot now. But some things you're unable to adjust. but that's where other treatments come in.

Yeah. So lifestyle matters, for some people, matters more than for others. There are things that are probably fairly universal like sleep where it really makes sense to focus on that. And for others could be a wide range of things that do or do not trigger a migraine, completely dependent on the individual. You brought up ketamine before also, which I think is really interesting because, you know, psychedelics in all sorts of forms. The volume of research that's going into them

for a variety of different conditions is kind of incredible over the last 10 years or so. Talk to me about ketamine or just the general class of psychedelics. And I know some people debate whether ketamine actually should even be in the class of psychedelics.

I don't think ketamine is classified in psychedelics. Ketamine is an MDA. And again, I want to stress this is not a first line treatment. Yeah. You know, this is where others, this is for those who are very refractory headaches. But we believe that ketamine functions to help reverse this concept of central sensitization.

So central sensitization is, you know, sort of the, you know, you can think of it in a very simple way of how, like, the brain is adapting to migraine and more susceptible to migraine attacks. We know it works a variety of different receptors in the brain, one being GABA. GABA is brain injury. Gabba glutamate, like we view these as brain energy. So the brain doing a lot of signals. So, you know, and therefore bringing those down reduces how many transmissions are going and reducing the headache. We're not fully sure, of course, what it is. This is, you know, there's no test to prove it, but that's the general understanding.

Psychedelics, you know, I want there to be more research in psychedelics for migraine. There's been evidence in other countries of psychedelics for the treatment, like LSD for the treatment, of cluster. You know, I know some groups are beginning to underway with looking at it at migraine and cluster in this country. I believe the federal administration recently did an executive order to sort of, you know, speed that up. I, because of its effect with cluster, it makes it hopefully a promising treatment. But I guess all the topic of illicit, you know, treatments, marijuana does have a lot of evidence. There's been many, there's been two or three major trials. done. So it does have a medical medicinal purpose, but it has been shown that marijuana can be an

effective migraine abortive medication. These are things that we're on the edge of knowing. They're kind of like, and some you could call them fringe, but maybe for the research is really going to prove them out. When you look five, ten years out, what are you seeing in the research pipeline now that really may too excited? That's not yet a. available. The impact and success of the seizure-bid drugs have flung the doors wide open, which is great because, again, those were the first treatments that were specifically involved treating migraine and the fact that they were so successful that now there's a lot of attention. For instance, right now we have, there's ongoing trials for a neuropeptide called Paycap, P-C-A-P-A-P-P-A-P-P-Rae. So it's

another neuropeptide related to migraine. There are ongoing trials right now. So I hope within the next two years we have a whole new treatment class. There is, I also saw a presentation of the American Advoc Society about one that targets histamine because you know histamines involved. There's a lot of different potential neuropeptide and other enzyme targets that I think if we did this video 10 years from now, there will be a lot more treatments to talk about and a lot more success. Because the kind of thing gets brought up for it.

there are people who have migraine that the CGRP drugs didn't help at all. What does that mean? I thought CGRP was involved in migraine. But I believe, again, migraine is complex and that if we know there's a bunch of neuropeptines involved, I think there are individuals who have migraine attacks that aren't super CGRP driven. Maybe they're driven by a different neuropeptide. So what I really hope to see is when in a couple of years we hopefully have a pay cap drug that's out for those people whose seizure peas didn't help, this can hopefully be

an effective measure. And then that breaks the question, what do you combine some? What do we target both pay cap and seizure P? What does that do? Now, this is why we need clinical trials, like, you know, to make sure we're not scrambling brains, but I will say the seizure P drugs, the model clodos have been out since 2018 and there's not really been a vast increased signal seen in concerns. There's the FDA released post-marketing warnings that they may, may lead to increased blood pressure. Anecdotally, I've really not seen it that much. But there's been no contraindications.

Nothing's been polled. So they're relatively pretty safe drugs, and we're at the eight year mark. And again, it's only one peptide class we targeted. What do we reach a world? We have three or four. So it's very exciting stuff happening. Yeah, I mean, it sounds like you just described.

If we have this conversation again in 10 years, we could have a whole new suite of opportunities of offerings to draw upon and maybe even bring together. I can't tell you how many patients who said they last saw a provider about the headache, let's say, in the 90s, and they were like, I was reluctant to come back because what am I going to do? I'm like, let me tell you, it is a diff. We're in the golden age.

Like, you know, there's a lot of things we could do. I can't say it enough. If you're suffering from really any kind of headaches, speak with your provider, there's a lot that can be done. Last question about maybe less conventional approaches. I have read, and I'm sure a lot of people have read, like years ago, guys like Dr. John Sarno came out with his theory around TMS. And then more recently, Howard Schubiner, with MBS, Mind, Body Syndrome. And it's this notion of, I recently spoke with a researcher from Stanford who used the phrase biopsychosocial.

in reference to just generalized pain or chronic pain. Is there something potentially bigger going on that can lead to migraine, whether it's relational or social or psychological, that manifests in pain in migraine? Pain is a concept, if you will, a creation of the brain. Your body doesn't feel pain. Pain is a warning that's something. something is wrong in this area. If I cut your foot, it's pain to make you look at your foot. Oh,

if there's injury, I need to do something about it. Pain in my stomach, I eat something bad. I'll give an example, IBS. If you do a colonoscopy, endoscopy of someone IBS, it usually comes out clean, but then why is their stomach acting like this? The brain controls all. With that said, it's not just going on this, oh, it's in your head. The symptom is real. It's very real. going to treat the symptom. Just saying it's in your head. Every pain is in your head. If I cut your foot off, the pain is in your head. It's a manifestation of the brain, if you will. So yes, that's what goes back to this concept of chronic sensitization. When the migraine goes and treated for a while, your brain enters this sort of, you know, new environment. This is where things, like, let's say

you have a thermostat at home, but it's broken. Well, room temperature 72, it thinks it's room temperature, but it's really 82. Okay, the house is hot. But the thermos that says, we're good. Think of it like that. When you've had untreated migraine so long, your brain thinks this is normal. This is a normal way to feel. I'm supposed to feel this way.

And that's where things like biofeedback therapy and other psychological therapies come in. And it's, again, not saying that, oh, it's in your mind. Your brain is thinking of pain wrong. And it doesn't mean that everyone needs that kind of thing. But yes, those get involved. You brought up TMS. And TMS can also have its purpose as well. There's ones that are given in an office setting and some that are going to be giving, you know, home setting.

And, you know, they can work on numerous different pathways. But the point being is that it's not like, it's not as simple as, you know, brain has pain. It's more complex than that. And again, it comes to your brain, how your brain handles certain stimuli. Another example or thing to bring up is so depression is the most common comorbidity for migraine. Why? Why is your mood, if you will, I'm not down. I'm saying this simplistically.

I'm not trying to downplaying any with depression. Why would that cause pain? Well, depression, anxiety, that's stimulus. It's also noxious stimulus. Then it's not good stimulus. The brain starts seeing that as bad stimulus. Again, what do we say pain is? So there's bad and therefore the brain thinks in the state of danger.

and now we're having a painful syndrome. And this is a big oversimplification, you know, very oversimplication. And we don't fully understand. We don't. If we knew exactly causes whatnot, we would cure migraine. But this is what we, throughout a theory of how it's sort of interacted. Yeah. So for someone's been joining us, this conversation,

and you just went through just incredible depth in what migraine is, is in how we start to distinguish these from different types of headaches. and the different ways that you think about acute versus preventative and also lifestyle and beyond and what's coming down the pipeline. So somebody's joining us, kind of nodding along, fascinated by this, and maybe there's somebody who's been dealing with migraine. Maybe they've just realized for the first time in this conversation, oh, wait, this actually, I think maybe migraine.

And maybe there's actually something that I can do about this. But they don't know where to start. What would you tell them? Like where do they step into this? Your private care doctor is always your first place. And, you know, I always say patients are their own best advocate. If you're a primary doctor, you know, make sure you make in the case that how it's affecting you, if they're shugging you're off, sounds like you need a new primary care doctor.

You know, headache medicine specialists exist. You've always go to general neurologists. There's people like me who report certifying a headache medicine. You could use resources online like at the National Heading Foundation and the American Migraine Foundation. A resource is to connect you with the board certified headache specialists. I run a headache, like education blog on my website, Headache 1,23.com. So I would summarize it again as, you know, be your best advocate,

bring them to your paramed care doctor, and then just seeing if there's a headache specialist in your area. It could take a while to see when they typically have long wait lists, then that's why starting with your primary care doctor. But you feel this is affecting you. You're not alone. You know, up to 60 million Americans have thought to have migraine. And many more are untrue.

or unknown that they have it. It's super common and there's things we could do. I love that. It makes the person who maybe has felt a little bit hopeless realize, even if maybe they'd seen somebody a long time ago, times have changed and there's probably a lot more that can be done to help you out. I can't say it enough. I feel I'm very fortunate. I love my job. You know, there's so much we could do in headache medicine. Love that. It feels like a good place for us to come full circle as well. So I always wrap these conversations with the same question in this container of a good life project if I offer up the phrase to live a good life. What comes up?

To live a good life is, you know, finding ways to not let chronic conditions, you know, be down. And that's harder, that's easier said than done. But, you know, your patient medical journey never ends and always finding the best care you can get. Thank you. So the thing I'm sitting with from this conversation, is how long that the blood vessel story stuck around and how many treatments, including some that I've tried myself over decades, were built on it. A few things I don't want you to lose also. The broken thermostat idea, this notion that untreated pain can quietly convince your brain that this is

just normal now, or the migraine hangover, that whole body exhaustion after an attack that's actually your brain running out of fuel and the golden age. Dr. Cohn's phrase, not mine for where headache medicine actually is and is going right now. So here's the concrete thing for you this week to think about. If you or somebody you love has been living with head pain, with migraine or headache, and assuming there's nothing left to try or hasn't seen anyone about it since it felt hopeless years ago, that assumption is probably out of date. Start with your primary care physician or your closest qualified health care provider. That's it. The whole first step. And hey, before you leave, next week, we're sitting down with Marissa Renee Lee to talk about

why the tidy stories we tell ourselves about grief and resilience, they tend to fall apart and what it actually looks like to build a life around pain instead of just waiting to get past it. So be sure to follow a Good Life Project wherever you get your podcast, so you don't miss that or any upcoming episodes. And do me a quick favor while we're here. Share this episode, especially anyone who is either personally suffering with or knows people, has people around them that deal with these things called headaches or migraines. This can be incredibly helpful and eye-opening for them. And while you're at it, if you have three extra seconds, go ahead and leave us a quick review wherever you get your podcast. This episode of Good Life Project was produced by

Grigative producers, Lindsay Fox and me, Jonathan Fields, editing help by Troy Young, Chris Carter, crafted our theme music. And of course, if you haven't already done so, go ahead and follow us wherever you get your podcast, so you never miss a conversation. Until next time, I'm Jonathan Fields, signing off for Good Life Project.