This is our yearly medical update lecture, focusing on a medical problem that we see clinically and asking an expert in her field to come teach us about it. So, today we're so fortunate to have Dr. Tisha Mae Monteith, who's a professor of clinical neurology and chief of the headache division at the University of Miami. Tisha completed her medical education at the University of Miami, and then she came up to New York to do her neurology residency at NYU. And, funny story, she actually applied for residencies both in psychiatry and then the psych-neuro combined and neurology, and she chose neurology, but she was this close to becoming a psychiatrist. So, while she was a resident at NYU Bellevue, she also was a moonlighter in the CPEP emergency room, and so she knows our patients quite well. And now, she then did a fellowship focusing on headache management. She's an active researcher and lecturer. She has served on advisory boards, conducted clinical trials, and received NIH funding. Dr. Monteith is the president of the Florida Society of Neurology and has been recognized with multiple awards for her contributions to education, advocacy, and science. We are so fortunate that she's here today because after our talk, she's catching a plane tonight to Scottsdale for the American Headache Society Scottsdale Symposium, where she is receiving an award in women's health sciences. Congratulations. Thank you. So, today, I've asked Dr. Monteith to keep it fairly simple, that we are psychiatrists, we're not neurologists, and she's going to stick to the main topic of migraine. There's not a lot of time for the biology or to discuss traumatic brain injury, but she can take questions on those during the question and answer. So, today, thank you for coming, and she's going to speak on migraine and medication overuse headache. Thank you. Thank you for the warm welcome and introduction. It's a real honor to be here, and I'm delighted that there's this organization that focuses on caring for people with addiction because we know that it's a massive problem. And, of course, migraine is a massive problem, so therefore the overlap is a massive problem, and we don't always get together to really think about this. And so, hopefully, my talk will help. So, these are my disclosures, a number of industry relationships with drugs that will be discussed in our talk. The main disclosure is I'm not a psychiatrist, but I do have a lot of friends that are psychiatrists. So, for the objectives, the main thing is to understand that migraine is massively disabling, and it's extremely common. You're certainly treating people that have migraine, and you certainly know people, and many of you probably also have migraine. And so, if you recognize and come out of this talk recognizing how to diagnose migraine, the impact migraine has on the individual and society, that alone will be a win. But we'll also talk about how to manage it with basic treatments, both non-pharmacological treatments as well as pharmacological interventions. And we'll spend some time talking about medication overuse headache and this idea of an overlap with addiction when there is an overlap. So, the first thing to know is migraine, again, is hugely common. It's a leading cause of disability worldwide, a top cause of disability in all diseases, but certainly in the list of neurologic diseases. It is the third most prevalent medical disorder. So, the third most prevalent medical disorder, that is a lot. Before then, it's tension type headache and dental cavities. Okay? So, we're busy people. So, the international classification of headache disorders is now in its third edition, and if you're very interested in learning about migraine, recognize that migraine has many subtypes. We'll talk a little bit about chronic migraine, but there are many subtypes. There are other primary headache disorders out there that we're not going to be talking about. And there are secondary causes of headache that we are always thinking about in the back of our head because we want to make sure that there's not a reversible problem or even potentially a lethal problem. We're not going to be talking about cranial neuropathies and things like trigeminal neuralgia, but this is all available for you in the international classification of headache disorders, and it's freely available online. So, migraine affects people of all age groups. I have some patients now in their 60s that felt like they were born with migraine and they were symptomatic since they first recalled being in existence. So, it's a lifelong disorder. It generally affects people in their most productive ages. So, this is in the 30s and the 40s. When you're maybe in the midst of your profession, having children, there are other stressors and financial responsibilities going on. There's a female predominance for migraine, so two to three times more common in women than in men, but also not uncommon in men. And the good news is that usually as people get older, there's less prevalence of migraine. But of course, there's a female predominance. But of course, there's the transition period, perimenstrual period, that people can sometimes have more migraine before things get better. And certainly, we have adults that are older, in their 60s, that's in their 70s, that are still experiencing a lot of disabling migraine, and that's the group that has a huge unmet need. Post-traumatic headache can sometimes look like migraine, and as mentioned, we won't really be able to talk about that, but these are some of the risk factors for why people may go on to have more frequent headache when there are things like injury and concussions that are happening. So, social determinants of health is important. It's important, I think, probably for addiction and certainly for neurologic disorders like migraine. And we know that there are risk factors for people that have more frequent migraine or chronic migraine, those in lower socioeconomic groups, those that are underinsured, those that might be exposed to domestic violence, those with food insecurity. So we don't always do a good job of screening for social determinants of health, but it's a good idea to think about it, especially if you have a patient that's missing a lot of appointments and has a lot of migraine. The frequency of migraine can vary. It's considered a cyclical brain disorder, so people can have periods of time with lower frequency of migraine attacks and then other periods of time with higher frequency of migraine attacks. Sometimes we're able to pin that down, but many times we're not because it's a cyclical disorder. This slide is really just to let you know that there are massive barriers to care for migraine. If you have episodic migraine, that is defined as having migraine up to 14 days per month, or if you have chronic migraine defined as having 15 headache days or a month for at least three months, both categories face a lot of barriers. So I think this is where you kind of may come in and you may be the first one to diagnose someone with migraine. The first barrier is getting a consultation. We know that in my clinic, I have people that sometimes wait a year to see me, and there's not enough headache specialists. In some states, there are no headache specialists. We have many neurologists that may or may not treat migraine. They may be specialized in other types of neurology. So this is something that we all need to get a handle on. If you take episodic migraine, we mentioned getting a consultation and then getting the diagnosis, getting the very minimal appropriate migraine treatments, which includes acute treatments and preventive treatments, and then not having medication overuse headache, which we'll talk about. So if you're able to traverse those barriers, it's a small number, less than 10% if you have episodic migraine. The number is also very low, less than 2% if you have chronic migraine, which is the more disabling type of migraine. Overall, there are massive barriers of care. There's only about 10% of individuals in our population, at least according to this well-done CAMEO study. And so we need to do better at our diagnosis. And if you, as a medical establishment, are able to help at least get that diagnosis and even start with some initial treatments, I think that will be very helpful for our patients. So migraine diagnosis, just, you know, something that I think many people know intuitively, but this is according to the classification. The classification, it's important to know, is a symptom based classification. So it's not based on biomarkers. We don't have biomarkers. It's not based on MRI of the brain. We have many patients that want MRI to diagnose their migraine. We use MRI sometimes if they're a concern of a secondary disorder, but you certainly don't need an MRI to diagnose migraine. So patients have moderate to severe headache. Four hours to three days is typical without treatment or even with treatment. And then there's some other care classification that you should know about. Unilateral headache, pulsating headache, movement sensitivity. These are things that patients may have. If a patient does not have unilateral headache, they can still have a migraine. There's a lot of people, and I've heard medical professionals say, okay, it's bilateral. It must be tension type headache. So we know that migraine is underdiagnosed and that if we really better understand the classification, we're better able to help our patients. So you can have bilateral headache. It doesn't have to be severe with a lot of nausea and vomiting. They can have light sensitivity or sound sensitivity. What's important is that it can sometimes be mild, and they should still make that diagnosis even if it's mild and even if it's not present with all attacks because we know that migraine can be a varying disorder. And then for chronic migraine, we mentioned 15 headache days or more for at least three months. Eight of those days are generally meeting criteria for migraine. So these are patients with a lot of disability. And then 50% of people with chronic migraine have medication overuse headache. And so medication overuse headache we'll talk about, but about half of our patients you should ask. Now, the reason why chronic migraine gets underdiagnosed is sometimes patients are telling you about those eight days that are really severe, but they don't tell you about the days that are moderate or they'll deal with it. It's not keeping them out of school or out of work. So they just ignore those. And sometimes if you ask patients, well, how many days are you crystal clear, have zero headache, none at all? Never. I don't remember the last time I had anything like that, but those don't bother me. So, you know, it's important because then, you know, you miss the diagnosis, you miss the level of disability, and then the treatment strategies may be a little bit different. So these are some of the subtypes of migraine, which really not going to go into the main one being migraine with and without aura. There are the episodic syndromes that patients may experience. These are often recurrent disorders that are common in childhood, but may happen in adulthood as well. Status migranosis, that's when someone has migraine more than three days, and that can be persistent for two, three weeks at a time. So if you're busy and you don't have a lot of time, there's a lot of different discussion points that you have with your patient, but you think that they may have migraine, but again, you're super busy. There is a three-question screener that you can use called ID Migraine, and basically you're asking the patient, during the last three months, did you have a headache with any of the following? Light sensitivity, impairment, so that means just, you know, slowing down in your routine activities, and nausea. If they say, this is a pin, if they say yes to two out of the three, the sensitivity of having migraine is 93%. And so that's pretty huge. Now, in my clinic, I get a lot of people that may have other symptoms and they're more subtle, and with this pin, you actually could miss a diagnosis, but I think this is a good place to start, two out of three, photophobia, impairment, and nausea. And, you know, there's this acronym called SNOOP by David Dodick, and now it's like in version SNOOP 10. This is SNOOP 4, it just keeps going on, but it's a way to screen for these secondary problems that I know psychiatrists sometimes get a little bit nervous about. They may want to shy away from treating a medical disorder because, you know, it could be related to something else, and that certainly could be the case. But if you think about SNOOP, this acronym, do they have systemic symptoms or disease like HIV, weight loss, sweats? Are they older and getting the headache for the first time after age 50 or age 65? Is there a severe pattern change to their headache? Do they have focal neurologic symptoms? They're telling you they have weakness, they lost speech, they've lost consciousness with these headaches. The headaches are strictly on one side. These are things that say maybe there's something secondary that I should really get a neurologist involved or a medical practitioner involved in the care of this patient. So migraine, as I mentioned, is very disabling, but if you add the comorbidities of migraine, then, you know, that's going to be a greater impact. There are a number of comorbidities associated with migraine that put patients at risk for having this chronic migraine phenotype or make it more difficult to treat. There are a number of psychiatric disorders like generalized anxiety disorder is a common one, panic disorder, mood disorder, post-traumatic stress disorder, that when patients have these conditions plus migraine, they may be at risk for more frequent migraine. Pain disorders is another one that I think affects your population because we know that there are many people that get prescriptions for pain and then they become addicted to the pain medications. And so when patients have pain disorders, some of these medications may be used to treat the pain disorder, but it may also be used to treat the migraine. And then it becomes very complicated. It becomes almost a cyclical problem. So getting a good medical history is important and thinking about the things that may predispose people to more frequent migraine. And then as we're thinking about these comorbidities, they may be opportunities to potentially treat patients because we know if they have a severe sleep disorder or they have severe anxiety, it may be useful to treat that comorbidity and there may be common medications to that treatment that may actually reduce migraine frequency. So the International Classification of Headache Disorders does a good job of laying out the different medications that put people at risk for medication overuse headache. And this is based on expert kind of opinion. This is not really based on a lot of hardcore science. But, you know, generally speaking, we know that the treatments can be simple analgesics and so anything that's used 15 days or more, that's simple analgesics, puts a patient at risk for medication overuse headache. And then there's some that it's actually 10 days, which is about two or three times per week. So any more of that use puts patients at risk for medication overuse headache. And there are a lot of patients that say, well, if I combine these things and I'm going to take ibuprofen one day and I take a Triptan another day and I'll take Butabolol and I only take Percocet four times per month, is that really medication overuse headache? Yes, it is because there's a combination analgesic overuse that puts that patient at risk. So this is based on some epidemiologic studies and this was a review paper. Richard Lipton has done a lot of this work. And basically they show you that not every drug puts patients at risk for medication overuse equally. If you take the opiates, it's about eight days per month. Use of opiates even about eight days per month puts people at risk for medication overuse headache. So about a 15 headache day or more over time. And it seems to be more pronounced in men for opiates. If you take Butabolol, then even five days, five days of exposure of Butabolol, if you follow that patient out and you compare them to use of acetaminophen, follow them out for one year, you'll find that the people that are using Butabolol are at a much greater risk of having medication overuse headache. For Triptans, that seems to be true for those that have a lot of migraine. So if you have migraine 10 to 14 days per month and then you're overusing Triptans, you're more at risk. If you don't have that much migraine, you're not so. And interestingly, anti-inflammatory drugs have kind of two ways of response. One is a protective response. So if you are in that lower category, actually using anti-inflammatories may protect you from having medication overuse headache. And it can even be used as a preventive. But if your frequency is high, then you get in that category of potential for medication overuse headache. So the analgesic use can be driven by migraine. It can be driven by pain disorders or recreational use. But at the end, the increase often continues. And in some patients, they get put in this category of chronic daily headache. So I was told to keep it simple, so thank you. I can just skip this complicated slide. We don't really know how opiates work and how they target medication or how they exacerbate primary headache. It's important to say that those that have medication overuse headache have primary headache as a preexisting problem. So we have people in rheumatologic clinics that they're using these medications for joint pain and they don't have preexisting migraine. They're unlikely to get medication overuse headache. But those that have the genetics for migraine or migraine themselves are the ones that are most likely to get medication overuse headache. So there are peripheral and central mechanisms that are involved in this process. And again, also going to skip this slide, but I think what's important is that this is a full brain disorder. There are many factors, many parts of the brain. Some of those brain structures that are important for addiction are also a part of the pathway for medication overuse headache. And this was a paper in Nature Reviews if you want to check it out. And then this slide also from the same paper shows there are a number of cellular adaptive processes that are important. And some of this has to do with targeting the condition pain modulation as well what we used to call DNIC. There's also sensitization that occurs. So these processes can explain some of the changes that happen when people are overusing analgesics. So this is a patient that we see in clinic and she basically comes in. She has headache a long time, a continuous headache. Every day there's some headache. She's tried a number of things. She's a type of patient that has the pain comorbidity, fibromyalgia, psychiatric comorbidity, anxiety, depression. She's tried a number of oral therapies, amitriptyline, intrapyramide, and has not helped. She takes escitalopram for her anxiety and depression, but her symptoms persist. And she's also overusing a lot of acute treatments, butalpatol twice per day, sumatriptan two to three times per week, and ibuprofen daily. So this is a person with chronic migraine and medication overuse and a number of comorbidities. So I think backing up, we think about goals of care. How do you approach patients, even patients less complicated, how do you approach patients that have migraine? The first thing to recognize is that most patients benefit from some type of acute treatment and most of the time that's going to be a pharmacologic agent. Patients want pain freedom quickly, so we look at two hour pain freedom, consistency of use, and sustained response. Those are the biggest ones. Having the migraine go away within two hours and then stay away for two days is ideal for acute goal of care. So about almost all patients would benefit from optimizing acute migraine care. And so that's something we should recommend to all our patients and we'll talk about different options. Preventive therapies, generally speaking, the American Headache Society guidelines suggest that if you have four migraine days per month, you would benefit from a preventive approach. Now that can be pharmacological or non-pharmacologic, but if it's four days once a week, or if you have less migraine, less than four days, but you have disability with at least one of your attacks, you would also benefit from preventive therapy. So this is a slide that shows you the different interventions, pharmacologic interventions and non-pharmacologic interventions, and it's important to think about personalized approaches. Not every patient wants a pharmacologic event intervention. Some really love the devices. We'll talk about the devices. Of course, lifestyle factors are important. We don't have a lot of data for lifestyle factors, but there's data out there. But not everyone's going to be compliant with lifestyle. So thinking about these different strategies is important. And we'll go into some of these a little bit closer. So always talk to your patients about lifestyle factors. I think it is really important. We know things like aerobic activity can be helpful and can reduce migraine preventively. People that have insomnia, if you target the insomnia in people with chronic migraine, their migraine frequency can get better, and that's data driven. So these are six devices that are FDA cleared for prevention, mainly all for acute treatment of migraine and almost all for prevention. The one that's not yet data driven for prevention is the combined occipital trigeminal nerve stimulator, the Rolivion, that's the wrap around the head. All the other five have indication for acute and prevention for migraine. So these are things that if you want to avoid drugs in your patients, and the patients can afford these devices because it can be cost prohibitive, but if they can afford these devices, it may be useful for our patients. So the calcitonin gene related peptide, this is one of the molecules that has a wonderful story. From the 1980s early on, this is a molecule that we stole from dermatology. CGRP is also one of the, or is the most potent vasodilator in the human body, and there's been a number of experiments showing that calcitonin gene related peptide is important in the migraine pathophysiology. There are now a number of molecules, a number of drugs that can target CGRP, and we'll talk about those therapies because they really have a nice role in clinical practice. And I think as psychiatrists, this is something you should feel very comfortable prescribing, mainly because the side effect profile is so benign. So I'm not going to go through this slide, just recognize that calcitonin gene related peptide is involved in the brains of people with migraine. It's a factor molecule that gets released during acute migraine attacks, and there have been a number of therapies, and it took a long time to get to the ones that we have now, but that show that clearly blocking CGRP, either the ligand, the peptide, or the receptor can be therapeutic for people with migraine. So there's two different general classes of therapies. The small molecule, also known as G-PANS, it's very small, could get in the brain. And we also have the monoclonal antibodies. The monoclonal antibodies, are any of you, all of you familiar with these types of drugs for, I mean, there's now lots of commercials. So the small molecules, these are the G-PANS, so we'll talk about the G-PANS. And then the monoclonal antibodies, it's thought that the monoclonal antibodies don't pass the blood brain barrier, they're too big, how could they do that? Even though there's some smart people that say small amounts possibly could, they do find their way in the CSF, and so that's interesting, but generally speaking, they probably work in the periphery. So we have CGRP receptor antibodies that target the receptor, the different subunits of the receptor, as well as the ligand. There's four of these CGRP monoclonal antibodies, three of them are home injections, so patients can inject once a month and get relief to prevent their migraines. And there's one infusion, ebtenazumab, that they would have to go to an infusion center and get that every three months. And then the G-PANS also block the receptor, but again, it does so as a small molecule. So these are the four monoclonal antibodies that are available. They have long half-lives, they're around for one month, and they generally speaking have very little side effects. Across the MABs, at least the injectable ones, they can cause injection site reaction, which is very common. Maybe half of people can have some kind of reaction where they inject. It's pretty rare to stop the therapy because of the injection site reaction, so it's generally thought to be mild. Anyone can get an allergic reaction. Arenamab has a little bit more constipation, and there's a risk of hypertension with arenamab as well, and possibly alopecia. So why are people excited about these therapies? They're once a month, so they're convenient, but more than being convenient, they're highly efficacious. They have quick onset. They show a benefit as early as one month. So unlike some of the oral therapies that patients, the tapiramides and the valproates and amitriptylines, where you have to go slow and build up over a period of time, this is a once a month injection, and generally speaking, patients are going to generally have a positive response within three months when they see you back. The responder rates is excellent when compared to the prior oral therapies. We talked about safety and tolerability. These can be effective in people that have medication overuse headache when they have comorbid depression or anxiety, so the clinical trials really support its use for prevention. And if a patient has a 50% response, it's a good reason to continue patients on the therapies. The European Headache Federation guidelines suggest that keeping patients on therapies for 12 to 18 months is a good trial period or period of time, and if they do very well, you can consider stopping the therapy. So the American Headache Society has a consensus statement, and we'll talk about the more updated consensus statement, but it includes acute treatments and also includes the preventive therapies, triptans. We have seven triptans that are available to use, and these are things that are first line treatments, sumatriptan being the first one available in the 1990s, and followed by six other triptans. Triptans are mainstay treatments for, so even though we're talking about some of the newer therapies, triptans can be very effective, but they do have side effects and more side effects than some of the newer therapies, so they can be very effective, but associated with side effects, and we know that there are about 30% of people that don't respond to triptans, and so that can be problematic. Combining therapies can be very helpful. In terms of opiates, opiates should be avoided, and certainly never used as first line in people that have migraine. Now there may be people that have many comorbidities, they've had heart attacks, they've had other problems, and in very limited cases, do we recommend things like opiates. So let's talk about the approach to our patients, first with the acute treatment approach. So there's nonsteroidal anti-inflammatories that can be used, combination therapies, neuroleptics can be used, even things like Haldol can be used for our patients. We don't use them very often, but these dopaminergic blocking therapies can be helpful. So metoclopamide in combination with a nonsteroidal anti-inflammatory, in combination with a triptan for a patient that has moderate or severe headache, dihydrocodimine can be used, but oftentimes not used as first line. And then we have these newer Gpans, which we'll talk about. And then there's one drug called lasmitidine. Lasmitidine is a serotonergic blocking drug, similar to triptans, but instead of blocking 1B, 1D receptors, it blocks 1F receptor. So because it blocks 1F receptor, it is not vasoconstrictive. So lasmitidine can be used for abortive therapy for people with migraine, but it can cause a lot of sedation, so it's something that is limited. And then there's the FDA put a label on it saying that it has increased liking score, whatever that is. You guys should know more than me. So I guess patients took lasmitidine and felt like they liked being on lasmitidine, so they slapped a label on it. I don't think anyone takes that seriously, but it does have that label or warning. So Gpans, again, targets CGRP, and it's contraindicated in people that are on drugs that block CYP3A4. It can be used in people with cardiovascular disease safely, because it's non-vasoconstrictive. The nice thing about the Gpans is it doesn't cause medication overuse headache, doesn't cause that latent sensitization that we get worried about. So how do these newer drugs compare to the older drugs? Well, at least according to this large systematic review of 17 therapeutics, the tryptams actually fare quite well. And the tryptams have higher rates of pain freedom, two-hour pain freedom. In particular, alatryptam, risotryptam, sumatryptam, zomatryptam, more so than the Gpans. But we know that the Gpans are better tolerated, and again, there are a lot of people that don't respond to the tryptam. So how does the older drugs like topiramate compare to the newer drugs like orenimab, which blocks CGRP? And so this was a study that compared a head-to-head study. We don't have very many head-to-heads. This is the only one that I'm aware of, head-to-head study comparing topiramate to orenimab. Orenimab is the monoclonal antibody that blocks the CGRP receptor. And this study showed that topiramate or orenimab outperformed topiramate in terms of efficacy. Patients stayed on orenimab longer, and topiramate had more side effects. So, Topiramate still is the number one drug used for migraine prevention. It's something that you can start patients very small, 25 milligrams, and build them up slowly. But keeping in mind patients that may have, or that might be worried about a lot of side effects, these newer treatments might be better for them. So, again, it's a shared decision-making process that we have with our patients. Patients may be concerned about costs, and cost is certainly an issue with some of the newer therapies. Side effects can be an issue with some of the older therapies. Moodiness, I don't wanna be a guinea pig. Some patients don't want what's new, they want what's old and tried. And so, we always have to have a conversation with our patients. But things like weight gain, and many of these adverse events, are things that we're not seeing with some of these newer therapies. So, the American Headache Society came out with a position statement stating that the calcitonin gene-related peptide targeting therapies should be considered as first-line therapies for prevention. So, this is a list of different classes of medicines that can be used for episodic migraines. So, Tepiramate, again, very common. Divalprox may be a good option for patients, especially if they have comorbid bipolar disorder, beta blockers, for those that have hypertension. Candesartan is actually something, it's ARB, that may be very helpful for our patients for prevention, even if they don't have high blood pressure, right? The tricyclic antidepressants we often use for people that have sleep disorders or other issues. But, you know, patients are often concerned about weight gain with that class of medication. SNRIs, phenolfaxine, duloxetine can be helpful. I like phenolfaxine for my patients that have comorbid anxiety, for example. And then we have other therapies. We mentioned the monoclonal antibodies, now added to this list for first-line, as well as the G-PANS, because the G-PANS can also be used as preventives. So, what about chronic migraines? That group of people, like our patient, that has 15 headache days or more. Botox injections can be used for people with chronic migraine and not for people with episodic migraine. I think I skipped a slide. I'm sorry, I don't know what I did. Okay, there we go. Okay, so the preventive G-PANS, Atojipant, is cleared for, and there's data for episodic migraine as well as chronic migraine. And then you have Remegipant, which is a G-PANT that can be used for acute treatment of migraine, but can also be used as prevention if used every other day. And so that has a dual indication, and it's the first drug with a dual indication for both acute and prevention, and doesn't cause medication overuse when used every other day. So this is the Botox, and this is the injection sites for Botox. Any of you excited about learning? It's something psychiatrists certainly can do. It can also be combined with the CGRP inhibitors, and there's a synergistic effect with combining Botox with some of these CGRP inhibitors. So switching, if one MAB monoclonal antibody doesn't work after three months, consider switching. This was a study that showed that when you switch, 30% of the patients can respond to the second MAB. Then what happens when you stop patients? Well, there's gonna be a percent of patients that they revert to going back to having chronic migraine, overusing medications, and having more disability. The long-term studies are quite favorable. We know that these drugs are safe and highly effective, even in people that have used oral therapies, to Pyramid, and some of these other treatments, and have not responded. Long-term safety is excellent. Patients continue to have good benefit. There does not seem to be a disease-modifying benefit. So unlike some other drugs, like in the MS space, where over time you see patients get better, you do see patients over time get better with these CGRP inhibitors. There seems to be a cumulative effect, but if you stop it, they revert. Some of them revert back. Not all of them, but some of them revert back. So the European Headache Federation guidelines basically says that these drugs have strong quality of evidence, moderate to high, and this is across the four CGRP monoclonal antibodies. And it also says that when comparing Oranumab to Pyramid, as the data showed, that Oranumab outperforms the Pyramid. So we should consider using CGRP inhibitors as first line. Now, insurances don't always agree with us, but there's a number of insurers that are now picking up this on their kind of recommendations. Consider antibody switching. These are generally very safe. And even in people that have medication overuse headache, consider using this as a therapy. So we have that. So what about strategies for those that have medication overuse headache, and there may be, yeah, that's fine, I think this is the last slide. And so what about people that have medication overuse headache, and they are needing to withdraw? What do we do for those patients? So I think it depends on what country you're in, and what, you know, everyone has a different approach. But the more recent data suggests that trying patients on better performing therapies like CGRP monoclonal antibodies, you may not have to hospitalize them and abruptly withdraw them off their analgesics. So you may consider starting them on these newer therapies. You may consider withdrawing. There's certainly evidence for withdrawing, and then putting people on the preventives. But the strategies are very similar in outcomes. And I think the main thing to take away is that some of the newer therapies work well because the disease is driven by untreated migraine more so than it is the overuse of the analgesics. So, you know, stay engaged with us. There's a number of opportunities. If you're interested in learning about migraine, if you wanna be part of our team, you know, I'm happy to talk to you individually. And, you know, my conclusion is that, you know, migraine is common, it's very disabling. There are a number of strategies to try and help people. We talked about goals of care. We talked about different treatments that are available. It's very personalized for patients. And there's a lot of unmet needs. So even though you start someone on something, it is a chronic condition that requires frequent tailoring to get patients better. Thank you. So I think we'll have 15 minutes for any questions. I'm happy to take questions. I was just wondering, how much of a concern is there about use of SSRIs contributing to chronic headaches in people? Is that something that? Yeah. And so, I mean, I think it's a chicken or egg thing. Do they get headaches immediately after they started the SSRI? Or is it someone that had longstanding migraine and maybe they're fluctuating a little bit? And so I think that is something that we don't have good data on. If you look at almost all medications, it says headache as a side effect. It's not generally something I'm concerned about. If someone, two weeks after starting an SSRI developed headaches for the first time, yes. I'm more concerned about the discontinuation syndrome that people can have and they can, so that sometimes requires very slow tapering of medications. But we always have to think about that when people have new onset headaches. But oftentimes that's not the full story. Good question. What's the, over here, what's the current state of evidence or lack of evidence with cannabis and cannabinoids? And in particular, what do you say to your patients and say, hey, this really does seem to work for my headache? Yeah. So I think the current state is still an open question. We don't have good studies. We have a lot of retrospective studies. So now you're already tailoring out the people that think it's helpful. We have survey studies. There was a recent abstract that was presented at the American Academy of Neurology this year suggesting maybe there was a benefit, but they enrolled people that had used it. This was in California that had used it in the past. And so I don't, and if you ask me, most patients will not say that it helps their headaches. Most patients will say it chills me out, makes me feel better, makes me sleep, may help nausea. But it's rare that I have a patient. Now, of course, maybe there are patients out there that will never see me because they're using this. We do need to learn more about these receptors and the potential for medication overuse or cannabis-induced headache. I think it's just the data is not available. Good quality data is not available. Two brief questions. You didn't comment much on auras before migraines. What's the frequency? What percentage of people have those? And number two, do you ever see behavioral prodromes as part of an aura with lethargy, irritability, et cetera? I'm sorry, what was the second question? Lethargy and irritability as a behavioral prodrome. Yeah, yeah, great question. So the first question is about aura. How frequent is aura? About 25 to 30% of people with migraine have aura. Oftentimes it's visual, that's the most common. But people can have motor aura, also known as hemiplegic migraine. We have had patients that have hallucinations. I don't know if that's technically an aura, but that's a symptom of migraine. And so about 20 to 30% of people with migraine have aura. And your second question was about, I didn't talk about the multiphasic nature of migraine, and there are also non-pain symptoms outside of the classification. But it's very important to recognize that migraine is a multiphasic disorder. Before headache, about, and depends on the study, but a good 60% of people may have non-pain symptoms leading up to their migraine. This could be mania, this could be fatigue, this could be irritability. It could also be elation, and maybe they're more productive. And so recognizing these prodromal symptoms is important because it's an early sign of migraine, and if you treat earlier, your outcome is better. I have a question. I really appreciate your talk today. Thank you. It's interesting to me that medication overuse is used so often for people who get headaches often. So it's kind of counterintuitive, and maybe this is a rhetorical question, but like a diabetic who needs the medication on a daily basis, it's easy to come up with no answers if you're in a medication overuse. And I guess I would throw that back to you and ask, if the medication is actually helping, how is the medication overuse a problem? Yeah. So I think you probably asked 40 questions into one. But so the first statement was about those that are predisposed to higher frequency or more disabling migraine, they're more predisposed to medication overuse headache. Yeah, so I think the disease drives the analgesic overuse unlike recreational things, which is a separate category. And so people that have more frequent migraine are more sensitized, and we know that the overuse of medication adds to the sensitization. So it makes sense that it lowers that threshold to have migraine, and so it's not a problem to have migraine, and so that's why it can be problematic. And your other question was these medicines being like insulin. No one has a butabolol deficiency born with, right? So I think these are very, very different points. But people sometimes get to a place where they're, because of all these barriers, their migraine is not being treated appropriately, and they get on these therapies, and then it does become, we don't really use the term rebound anymore, but it becomes this kind of adaption problem where it's adapting probably on the receptor level, and then that medication is what gets you better for a short period of time. But over time, that increase changes, and the sensitization changes, and the opportunity to get better with better treatment is sometimes harder in the setting, because we know that people that are overusing medications, they don't respond as well to some of these therapies as those that are not overusing medications. Is there any role for TMS, or any research about TMS and migraine headache? Yeah, so one of the devices, we do have a device that is FDA cleared for, that is a TMS device. There's one specific device, so I don't know that all TMS devices are the same, but there is a role for that. It's thought to target cortical spreading depression, but also some of the cortical thalamic inputs and the thalamus itself. And there may be some endogenous opioid system that it's also targeting, which is very interesting based on some of the animal studies. What's the name of the device? It's eNura. The name constantly changes, but it's eNura. Hi, I had a question. So the student run free clinic at my school got a bunch of free topiramate, and it's just been sitting there on the shelf because nobody wants to use it because of the side effects. And so I was just wondering, what kinds of patients tend to do better on it and kind of tolerate the side effects better, if any? So your question is, what types of patients tolerate side effects better, specific to topiramate, or just across? Topiramate, like what kinds of patients might particularly handle it well? I'm assuming people who maybe don't have certain types of jobs. Yeah, so the most common side effect, so a contraindication is renal stones, and so we don't put anyone on renal stones. And then the most common side effect is, I think, paresthesias. And so that is something that you can write a prescription for potassium if a patient has paresthesias. Fatigue, word finding difficulty, brain fog, that's the biggest problem. And so, and we know that people with migraine, at least there's been some studies that suggest that, or maybe even report more side effects than the average person. But, you know, sometimes we put the dose at bedtime, and we don't do it twice a day, that's a way to work around it. It's hard to predict who's gonna have a side effect and who's not gonna have a side effect. Some people like the side effect of weight loss, and they're like, darn, I didn't get it. And so, you know, if people are very symptomatic to begin with, they have a lot of fatigue, they have a lot of word finding, all that baseline, then you'd think that they're probably more likely to report side effects. But you can always start small and go slow, and sometimes patients do get a good response. Yeah, I guess I was more curious, yeah, that makes sense, like what types of side effects make people want to stop? Because I've heard the cognitive is a big one, but in your experience, like which side effect would you say is the one that typically makes people? Yeah, I think the most common reason why people stop to Pyramid is it doesn't work. For some people, the ones that stop it. So I think that we have so many patients that have word finding difficulties, and they're willing to accept it, because it helps their migraine. But obviously, that is a major one for many patients, students, and people that are highly, high professional people that really need their cognitive function. And so I think the word finding difficulties tends to be the one that is the most, most people don't want to experience that. So I would like you to comment a little bit about nutrition and its relationship with headaches, because a lot of patients are very interested about that, and they don't want to take any medications, and they really have to deal with it. So great question. You're asking about the relationship between, and we're talking about migraine, not all of headaches, but the relationship between food and migraine. So migraine is a triggerable disorder, and we know that there are certain food triggers that can give people migraine attacks. Now, the problem with food triggers is that they're not always consistent. Now, one, that it tends to be very alcohol, right? And even, you know, there are a lot of people that will drink alcohol, and they know they're gonna get a migraine. And so things, I mean, there's a whole list of potential food triggers, and it's not equal to every person. Some people have no food triggers that they've identified, and so it's a very complicated thing. There's very drastic diets, like elimination diet. Most headache specialists don't recommend elimination diet. That means that you're eliminating all of these foods, and then slowly integrate them back, but they tend to be very drastic. So I think part of the problem is, now, if a patient can identify, and they track, and they say, 80% of the time I take something, I'm gonna get a migraine, then sure, go ahead, avoid it. So there's food avoidance that can be helpful for patients, but you do have to be careful. Now, we know that there's some popular ones, like nitrates, things that contain MSG, for example, a number of food additives that can be very triggering for migraine. There have been studies that have looked at food allergy testing, IGE, and there's really not a great evidence for that, and there's a lot of studies that have, or a lot of, if you look at these commercial kits that sell people food sensitivity testing, again, that's something that doesn't have good evidence, or even the science of IgG response is very limited, and the allergy societies don't recommend them. What is the current pathophysiology of migraine headaches? It used to be a vascular condition. It used to be, when we called it classic migraines, classically happening at the end of a stressful time, or when someone's in excess, not enough sleep, too much sleep, not eating enough, not drinking enough, drinking too much. So what's the current pathophysiology? Yeah, so great question, and you're giving me, I don't know how much time to answer that, but so migraine is a brain disorder. It's a neurologic disorder. It's a cyclical disorder, so people have thresholds to having migraine. It's thought to be a disorder of hyper-responsiveness to environment, but it's important to know that these are brain structures that are involved, and so it's no longer thought to be a vascular disorder, but it's probably best to think of it as a neurovascular disorder, where parts of the brain, like the hypothalamus, the thalamus, and the network, more of, you know, we talk a lot about network disorders. Migraine's a very classic network disorder, that there are disturbances that are neuronally driven, and there are vascular consequences, but these are not the primary cause of migraine, and so it's more appropriate to think of it in terms of a network disorder, I think. We know that there, and I removed that slide, but there's over 123 genes that are associated with migraine, so it's highly genetic, and there are many genes, both vascular and neuronal, and other types of genes that are involved in migraine. Thank you. Okay, thank you so much, hopefully that was helpful.

migraines

headache management

medication overuse

CGRP inhibitors

neurology

treatment strategies

diagnostic practices

genetic influences

lifestyle modifications

addiction disorders

medication overuse headaches

personalized treatment

comorbidities

neurological disorder

social determinants

pathophysiology