Migraine Relief: Providing Preventive and Abortive Therapies

Podcast Transcript

Neuro Pathways Podcast Series

Release Date: June15, 2024

Expiration Date: June 15, 2025

Estimated Time of Completion: 30 minutes

Migraine Relief: Providing Preventive and Abortive Therapies

Emad Estemalik, MD

Description

Each podcast in the Neurological Institute series provides a brief, review of management strategies related to the topic.

Learning Objectives

• Review up to date and clinically pertinent topics related to neurological disease
• Discuss advances in the field of neurological diseases
• Describe options for the treatment and care of various neurological disease

Target Audience

Physicians and Advanced Practice providers in Family Practice, Internal Medicine & Subspecialties, Neurology, Nursing, Pediatrics, Psychology/Psychiatry, Radiology as well as Professors, Researchers, and Students.

ACCREDITATION

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

CREDIT DESIGNATION

• American Medical Association (AMA)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
  
  Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)
  Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

• Certificate of Participation
  A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

• American Board of Surgery (ABS)
  Successful completion of this CME activity enables the learner to earn credit toward the CME requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider's responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit.

Credit will be reported within 30 days of claiming credit.

Podcast Series Director

Imad Najm, MD
Epilepsy Center

Additional Planner/Reviewer

Cindy Willis, DNP

Faculty

Emad Estemalik, MD
Center for Neurological Restoration

Host

Glen Stevens, DO, PhD
Cleveland Clinic Brain Tumor and Neuro-Oncology Center

Agenda

Migraine Relief: Providing Preventive and Abortive Therapies

Emad Estemalik, MD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Cindy Willis, DNP and Emad Estemalik, MD

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: Neuro Pathways Podcast June 15, 2024 to log into myCME and begin the activity evaluation and print your certificate If you need assistance, contact the CME office at myCME@ccf.org

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

Introduction: Neuro Pathways, a Cleveland Clinic podcast exploring the latest research discoveries and clinical advances in the fields of neurology, neurosurgery, neuro rehab, and psychiatry.

Glen Stevens, DO, PhD: The last decade has seen the rise of the first drug class to prevent migraines, calcitonin gene-related peptide inhibitors or CGRP. While simultaneously more abortive therapies have come to market. In this episode of Neuropathways will explore the current landscape of preventive and abortive therapies for the management of migraines with the goal of finding relief for all migraine sufferers. I'm your host Glenn Stevens, neurologist/neuro oncologist in Cleveland Clinic's Neurological Institute, and I'm very pleased to have Dr. Emad Estemalik. Join me for today's conversation. Dr. Estemalik is a headache specialist and head of the section of headache and facial Pain in Cleveland Clinic's Neurological Institute. Emad, welcome to Neuro Pathways.

Emad Estemalik, MD: Glen, good to be with you.

Glen Stevens, DO, PhD: So Emad, when I was training back in the day, there was really nothing specific to treat headaches. We gave people Tylenol, we gave them Advil, and that was it. And the very first medication came out, sumatriptan.

Emad Estemalik, MD: In the early nineties. That is right.

Glen Stevens, DO, PhD: Correct. In the early nineties. And sumatriptan, as you know, is a serotonin agonist and the theory was that headaches were secondary to vasodilation. So you'd give this vasoconstrictor and it would decrease the blood vessels and their headaches would get better and the migraine would abort and they would do well. And I think we understand better now that migraine probably associated with a trigeminal nerve and it activates this calcitonin gene-related peptide cascade. And maybe now in retrospect the sumatriptan probably had an effect on the calcitonin itself and maybe that's why it was making it better, even though we were thinking the wrong way, we got to the right place with these drugs. But is that what our thinking of migraine is or define migraine for us?

Emad Estemalik, MD: So you are correct. So first, our understanding about the pathophysiology of migraine has really evolved in the past 50, 60 years. Initially we had no idea what causes migraine and when you look at some of the really old literature, unfortunately some of you would interpret migraine as a hysterical disease because people would just get so much pain and nobody understood what it was about. Then our understanding evolved and you are right, it became more of a vascular phenomena. So we would think it is mainly about vasodilation in the brain and that is still true. I mean there is the vasodilation that does occur in the brain as well. To your point, sumatriptan, when it was developed, it is a serotonin 1B and 1D agonist. So it does affect the blood vessels and it does cause the vasoconstriction. So it does reverse migraines as well. But then we didn't move away from the vascular phenomena, but we understood that there is more than just vasodilation that occurs. And then the element of neurogenic inflammation, cortical spreading depression, that occurs as well in the migraine pathogenesis. So it is a trigeminovascular phenomena. Like you say, the CGRP came to light in the early 90s and 2000s. We just didn't have any drugs acting on it right away until 2018 when the first preventive monoclonal antibody was introduced. We only had mainly around the preventive therapies, meds being used to prevent and reduce migraine frequency that were not designed for migraines, anti-seizure meds, blood pressure meds, antidepressants, the abortives we had developed already several triptans, so we knew that they act on serotonin 1B and 1D and that would relieve migraine. But then really our understanding evolved from just looking at migraine purely as a vascular illness now to a disorder that has the neurogenic inflammation but also the vascular phenomenon on top of that as well.

Glen Stevens, DO, PhD: So when I came here in the early nineties, headache medicine was in Internal Medicine, yes, it was not in Neurology and subspecialists would have to see migraine at the time. And I remember one staff always used to say to patients, headache for you, headache for me. So we're very glad now that we have a very large and booming headache center that you help run. So thank you for that.

Emad Estemalik, MD: And we take a lot of pride in that. We run one of the largest headache centers in the United States. We have around 22 headache providers between physicians and advanced practitioners. It's an interdisciplinary approach. We see somewhere between 22-25,000 headache patients a year and we operate out of nine facilities including main campus to serve our patient population all over in northeast Ohio. And now we are in close connection and collaboration with all our domestic Cleveland Clinic hubs as well as the international hubs as well. We have our own infusion suite procedures units as well, and we work very closely with our neurosurgeons on various elements of secondary headaches that require neurosurgical attention as well.

Glen Stevens, DO, PhD: So it sounds like you're very busy, but now sounds like a really good time to have preventative medications as opposed to just abortive medications so that we can make quality of life for patients better. So somebody comes in to see you and they tell you that they have migraines. What type of symptoms do they have that would say, yes, this is a migraine or I don't think you have a migraine? 

Emad Estemalik, MD: Very good point because not everything that hurts in the head is a migraine. So it's very important for a headache specialist or a neurologist to make the distinction. A, to determine the right treatment and B, to determine if additional workup is needed or not. So when it comes to migraine specifically, again, it's very common unlike what a lot of people think. So roughly 16-20% of women suffer from migraine, tells you the magnitude and the penetration among the general population, 6-10% of men have migraines. But if you go by criteria, it is that 4-72 hour moderate to severe pain could be one-sided or all over the head. And then you have the classic associated symptoms of nausea, vomiting, lighter sun sensitivity, but the key to migraine that really distinguishes it from more simpler things like tension type headache is really the severity and the debilitating element that comes behind it. And when you have it in a chronic manner as defined as more than 15 headache days a month, you can really see the quality of life affected. That being said, there are also other primary headache disorders that should be distinguished from migraines. So we pay very close attention to unilateral lopsided headaches, only one-sided headaches. So again, you have a family of the trigeminal autonomic cephalalgias that have actually a very different pathogenesis as compared to migraine treated often very different and require additional workup as compared to a lot of the migraine patients that we see.

Glen Stevens, DO, PhD: Yeah, it's still surprising to me how many patients will say to me that obviously I look after tumor patients so people will, of course they'd have headaches, we actually don't see a lot of headache in our tumor patients and we'll see people that are very stable, but they'll come in and they'll say they're having headaches, but it's just sinus.

Emad Estemalik, MD: Absolutely

Glen Stevens, DO, PhD: Is what they say all the time.

Emad Estemalik, MD: You're absolutely right. Again, you are an expert on this as well when it comes to presentations for primary brain tumors or metastatic brain tumors, headache alone is rarely the sign of a primary brain tumor or a brain tumor in general. There are key other secondary elements that we can discuss of course and look at, but this is very important for patients to understand because the first thing a lot of times patients do when they have an increase in frequency or headaches they’ll, go on Google, you put in your symptoms and it drives a lot of anxiety for a lot of the patients. I've been doing this now for a little bit over 10 years, I'm yet to had a diagnosed brain tumor just based on headache alone. Now that being said, if a patient is concerned, it's of course the right thing to do to address it with your provider, but it's always good to reassure patients that headaches alone, whether in the pediatric or adult population, unless we're talking other more what we call scary neurological signs, headache alone is rarely the sign of a brain tumor.

Glen Stevens, DO, PhD: So it really leads me to my next question and that is imaging correct, which you've partially answered, but when do we image?

Emad Estemalik, MD: So what we typically look for, first of all, there are mnemonics that we all follow. If you take migraines, a lot of patients think if they have migraines, they ought to get the appropriate brain imaging to exclude secondary. That is simply not true. What you often see in migraines, you can see actually some changes in the brain. And with all the new advanced 3T MRIs, we can pick up a lot of changes in the brain, things like white matter hyperintensities, but they're not concerning and you often see them in migraine patients or patients who have vascular illnesses as well. Now there are signs and symptoms that can accompany a headache where we would say, yes, let's get, or we should get brain imaging. Example, positional headaches, headaches that worsen if you lay down or sit up. So we worry about increased intracranial pressure, often benign with vision changes in patients who have worsening headaches when they lay down. Headaches that are associated with Valsalva or movement or straining or bowel movement, sneezing, coughing.

We worry about things like posterior fossa, masses. Nuanced headache in somebody who's never had a history of migraines. Migraines typically don't just evolve in somebody who's fifties or sixties. So again, headache at an older age should be investigated as well. Headache that wakes you up in the middle of the night headache that is associated with significant visual changes or neurological deficit, cognitive changes, seizures, these are the things that we look for to determine if brain imaging is appropriate or not. And then finally, as we all remember from our days in med school, if you ever have the worst headache of your life, it's very important to address that immediately. Things like ruptured aneurysms, hemorrhages and so on, can be a factor here as well.

Glen Stevens, DO, PhD: So I know it's hard to believe, but I'm well past my sixties, so if I get a bad headache, I'm going to call you.

Emad Estemalik, MD: I thought you're 40, but if you have a headache you just come and see me.

Glen Stevens, DO, PhD: 40 plus, that's good, 40 plus. So discuss with us preventive therapy.

Emad Estemalik, MD: So preventive therapy, the idea behind a preventive therapy and we'll define what we do, is to reduce the frequency of someone's headaches and migraines and also reduce the severity of the actual headaches. So we go typically by headache days that a patient encounters when they have headaches or migraines. So again, chronic migraine is defined as having more than 15 headache days a month with eight of those having migraine features. And there's a variety of preventive approaches. There's of course the natural remedies, lifestyle modification. I talked about the historical preventives that we use, blood pressure meds, anti-seizure meds, antidepressants that can also address other comorbidities. But then since 2018 we have the new class of what we call the preventive monoclonal antibodies. These are revolutionary medication. We have three injectables on the market and one intravenous. They all act in the CGRP ligand or CGRP receptor. And then now we also have the small molecule CGRP antagonist very similar to the preventive monoclonal antibodies and they overlap between some acting as an abortive, or a rescue medication, and others acting as a preventive as well. Then we should never forget, one of the first procedures actually precedes the introduction of monoclonal antibodies, which is onabotulinum toxin that's been used now since 2008 when it gained FDA approval. That is another treatment modality that we use to reduce and prevent chronic migraines. And then of course there's a spectrum that's a longer topic we could have probably at one point neuromodulation for those who don't respond to any of these pharmacological agents.

Glen Stevens, DO, PhD: Where do you sit with magnesium? Are you a magnesium guy?

Emad Estemalik, MD: I'm a big fan of over the counter supplements. So magnesium oxide typically somewhere between 400 and 500 milligram at night. Vitamin B two riboflavin around 200 milligram twice a day and things like coenzyme Q10 150 twice a day. These are the three over the counter supplements that really, really help reduce migraines as well. It is important to note why do I love over the counter supplements because I do think you need to address also other comorbidities, lifestyle modification which can play a huge role. Take the stress that we all face, screen time overthinking things, anxiety, psychological elements, sleep hygiene, obesity. So again, lifestyle modification is, as if not, more critical than the introduction of any pharmacological agent.

Glen Stevens, DO, PhD: So if we look at the CGRP, and I hate to use the word insurance and I'm sure there's probably some algorithm that you have to follow.

Emad Estemalik, MD: Correct?

Glen Stevens, DO, PhD: What's the algorithm?

Emad Estemalik, MD: So the algorithms that we follow are not based on clinical or scientific data. In fact, the American Headache Society has determined, I think it was six months ago, that the monoclonal antibodies and the small molecule CGRP antagonists should serve as the first line treatment for migraine patients. In real life that is not the case. Most payers and insurance companies do want to see a failure or lack of response or side effect profile with the traditional, I call them traditional, but with the older preventives that we use. So the blood pressure, the anti-seizure and the antidepressants, a lot of patients do well with those, but the side effect profile tends to be very high. So yes, the algorithm is mainly defined by the payers and the reimbursement model that we look at.

Glen Stevens, DO, PhD: Where does botulinum toxin fit in this?

Emad Estemalik, MD: So onabotulinum toxin is approved for the prevention of chronic migraine. It is not approved by the FDA for episodic migraine. So again, it falls in that same category like the newer medication. So still if you want to introduce onabotulinum toxin, you got to kind of demonstrate that there has been a lack of response or side effect profile with things like blood pressure meds or antidepressants or seizure meds.

Glen Stevens, DO, PhD: So the CGRPs, how are they delivered? Are they delivered IV?

Emad Estemalik, MD: So the preventive monoclonal antibodies, the CGRP antagonist, you have three injectables on the market and you'll have one intravenous that's given every three months. The injectables are given every month and you have actually an injectable in one of them that's given every three months as well. So the IV is the only one that's given every three months. Then you have the preventive small molecule, CGRP antagonist, there are two of them that are approved for episodic and chronic migraine. One's for episodic and chronic, one is for episodic, the one that's for episodic and chronic migraine is an oral medication that you take every day. And the other small molecule, CGRP antagonist, it's a regimen that's taken every other day as a prevention.

Glen Stevens, DO, PhD: And I hate to ask this, but do insurance companies have you take the oral before you would take an injectable or an IV?

Emad Estemalik, MD: So that's a good question. The thing about what insurance companies require, it almost evolves from month to month and you see always these changes happening. I would say what we have seen in the past few months now is that yes, they do probably require the injectables to be tried first before you go to one of the newer ones, the small molecule CGRP antagonist. But again, a lot of things happen behind the scene with industry and payer. So there's always evolving negotiations and I travel all over the country and talk to other healthcare organizations. Every plan, every part of America has very different rules. And again, we see that none of that is consistent and it really changes with time.

Glen Stevens, DO, PhD: And side effects of the medications.

Emad Estemalik, MD: So when you look at the efficacy and safety data of both the preventive monoclonal antibodies and the small molecule CGRP antagonist, they do not even compare when it comes to the side effect profile of the, again, I'll go back to my word, the historical oral preventive. So if you're talking seizure meds, we all know the side effects with things like topiramate, whether it's cognitive side effect, prestigious weight gain with Depakote, weight gain and sedation with antidepressants, drop in blood pressure and dizziness with some of the blood pressure meds. When you look at all the monoclonal antibodies, again, the side effect were very limited and almost none comparable. 30-40% of our patients will have some cognitive side effect with a drug like topiramate, even if the drug works well, the discontinuation rate with some of these drugs is significantly higher. And even if you look at the efficacy and safety data of all these newer meds and the discontinuation rate among those trials is nothing compared to the huge discontinuation rate in some of the older medication when they were studied head to head or against placebo.

Glen Stevens, DO, PhD:

When things get out on the market and mass use of these types things, often you'll find new side effects. Anything popping up?

Emad Estemalik, MD: So there is, and to your point, so again, we always look at open label trials and then 52 week safety trials. There's for instance one of the injectable monoclonal antibodies that now has a black box warning for things like constipation and increased blood pressure. So we kind of will factor that in before giving that drug. We've seen some upper respiratory illnesses with some of the small molecule CGRP antagonist or some of the infusion, but still the most common side effect that always remain with injectables for instance is injection site reactions or erythema or some sort of rash. So again, yes you are correct with time user we'll discover more things, but they've been now on the market for such a long time that their safety profile is impeccable at this point.

Glen Stevens, DO, PhD: So if I'm a migrainer and I come see you and you're going to start me on one of these medications, how long till I'll notice a benefit?

Emad Estemalik, MD: So that's a great question because when you compare the quick onset and there's efficacy data behind that as well, they work much faster than your typical oral preventive. So when you look at the old guidelines for things like seizure meds or blood pressure meds would always tell a patient you got to give it at least eight to 10 weeks, titrate it up and then you should hope for a 50% reduction after 10 to 12 weeks. We have a lot of data with the preventive monoclonal antibodies and the small molecule CGRP antagonist where you have almost a very quick reduction in the first one week and then you also some have the data where you show you already had a 50% chance in reduction, 50% lesser chance of having a migraine even within 24 hours as well. One of the novel endpoints that were looked at as well were called the responder rates. So they looked at what's called the 50, 75 and a 100% responder rates and a lot of those drugs achieved actually what's called a hundred percent responder rates. That means within a three months period, a significant amount of patient, the percentage differs from one drug to the other and different trials, but a significant amount of patients had a month free of migraines within a three months period. So really we exceeded that 50% reduction in migraine frequency that we used to have with the oral preventives. So again, incredible efficacy, quick onset and sustainability as well for a lot of these meds.

Glen Stevens, DO, PhD: So on the negative side of that, I assume that if I'm not feeling any better in a couple of weeks even on it, I start to get a little depressed and I'm not going to get better. But how long is it if you don't get a response by three months, how long will you keep me on it before you say it's not going to work?

Emad Estemalik, MD: So if you don't see a response at all, that's usually a sign we should change the drug. But what some of the data shows as well, and I call that from a business term, the net aggregate effect, you've seen that some of the responder rates improve actually as we go within six to nine months as well. So you could achieve a 50% responder rate within three months, but some patients actually went to a 75% responder rate after that as well. Typically what we like to do is give it a six month trial if there's already some response of some kind and see how the patient does as well.

Glen Stevens, DO, PhD: So if I'm taking your friend topiramate, thankfully I'm not, but if I'm taking that and you come talk to me and you say, “Hey, I got this drug, I think we could try it.” So you start me on this drug, do I stay on the Topiramate for a month, two months, three months, and then once you determine this drug is going to have a benefit, you take me off the other drug or what's your general policy?

Emad Estemalik, MD: So usually it's up to a clinician judgment on how they do it. Typically, we want patients to be on the least amount of pharmacological agents in general. So, what typically I would do, I will start the monoclonal antibody see if a response and start tapering down in the next visit within three months. Now remember some patients take thing like antidepressants for other comorbidities as well. So if you have an antidepressant that was given because there's a mood component and migraines as well and you still want the patient to be on that medication for the reduction of anxiety or improving mood symptoms as well. It is not unreasonable to consider to continue a medication like that as well. But very important is often to sort out what's causing what a lot of patients are depressed or are anxious because they have a lot of migraines and vice versa as well. So really that good approach towards understanding where the comorbidities fit in is very important. Personally, I'm a fan of the least medication, the better if we can reduce the amount of medication for the patients, that's always the right thing to do.

Glen Stevens, DO, PhD: So outside of migraine starts to get a little bit fuzzier in terms of what people really have. But chronic tension headache, benefit of these medications?

Emad Estemalik, MD: So they're not approved. So the FDA did not approve any of these monoclonal antibodies or small molecule CGRP antagonists for tension type headaches, tension type headaches. Where it differs from migraine is that it does not cause debilitating headaches or debilitating symptoms or severe enough for patients to really drop all the activity. What sometimes prompts us to consider some preventive approach for tension type headache when it gets into a chronic nature, that means a patient comes in and says, you know what, 20-25 days out of the months, I do have a pressure. I'm not nauseous, I don't have vomiting, I'm not light and sound sensitive, but I do have some degree of headache. Then you're talking chronic tension type headache and that's where probably you could introduce a preventive therapy based on clinical judgment as well. But then you look for other comorbidities, how is sleep affected? What's the diet? Is there an obesity component? Is there mood symptoms? Is there anxiety? So really you got to address a lot of these things as well.

Glen Stevens, DO, PhD: And rebound headache, I imagine the same very pod of problems?

Emad Estemalik, MD: Very common. We actually understand the component of rebound or medication overuse headache quite well and there's already established data in terms of the amount and what medications would contribute to rebound or medication overuse headache. So even in a migrainer, the overconsumption, and when I say overconsumption more than two to three times a week of simple over-the-counter pain medication would introduce rebound headaches, any amount of narcotics, any amount of butalbital containing substances in a migraine over an extended period of time can transform them to having more chronic migraine, hence rebound or medication overuse headache as well. So that is a very important concept to kind of understand. And back to your point, back in the days, and I still see it with some physicians, the answer to headaches is well just take a Tylenol or Motrin every day.

Glen Stevens, DO, PhD: So if we move to abortive therapies safe to give taking these small molecule.

Emad Estemalik, MD: So the nice thing about the small molecule CGRP antagonist as compared to the triptans for instance, or DHE drugs is really three elements. The first one is they don't have rebounds. So even overconsumption of triptans can give you rebound headaches. That is not the case for the small molecule CGRP antagonist, the aborted family. Second, no cerebrovascular risk factors. So even in patients who've had a TIA or a stroke, you typically would want to wait anyways. These patients are not eligible for triptans or DHE because of the vasoconstriction. And then third, even in patients with cardiovascular risk factors, those small molecule CGRP antagonists are the abortives of choice because triptans are also contraindicated for those patients.

Glen Stevens, DO, PhD: So if you can't give a triptan, what do you use as an abortive?

Emad Estemalik, MD: So if you can't give a triptan or DHE, your small molecule, CGRP antagonists should be your choice for patients who have migraines but they're ineligible for triptans or DHE medication.

Glen Stevens, DO, PhD: Where do we go from here? What's on the horizon?

Emad Estemalik, MD: We're always trying to understand migraine better. CGRP is now of course the receptor of interest. There's now a lot of talk and research about the PCAP or the pituitary activating peptide that also has a vasodilation component as well. We're very early, there are no FDA or no drugs yet approved, but that is a molecular receptor that's also now under investigation in addition to more medications around CGRP as well. So our understanding of migraine hasn't stopped. But what I would say, and maybe that's where a lot of other service lines in neurology probably are jealous of the migraine world or the headache neurologist, is that the amount of new therapies and medication that has come out for treatment of migraine is like no other branch in neuro. We have witnessed probably the vast majority of new interventions. But again, it is exciting because we are not close to curing any neurologic illnesses from migraine to dementias to demyelinating to neurodegenerative diseases. So really I think these are some of the most exciting times, not just in the migraine world, but also in understanding neurological illnesses.

Glen Stevens, DO, PhD: So I'm going to keep an eye out for this PACAP, the pituitary adenylate cyclase activating peptide peptide. Yeah. Which my understanding is it is thought to live in the neurons of the trigeminal nucleus. So again, it just seems like targeting the same thing.

Emad Estemalik, MD: Correct, with a different kind of therapy or different medication that acts on it. So again, we'll see there's some ongoing research trials now for medication acting on that drug. We'll see where that leads us.

Glen Stevens, DO, PhD: If I am your patient and I have migraines and I take some abortives and this type of stuff, but how much is too much? Or maybe it's too individual for a patient. When should I go on one of these newer drugs?

Emad Estemalik, MD: I think two components. The frequency of abortive medication use definitely plays a role. I would say if patients are requiring more than two days a week of some abortive, I think it's time to consider a preventive to reduce the use of abortive medication. Second, I think it's often important to also pinpoint exactly the number of headache days. A patient can tell you, I only have four migraines a month. And if they're not adequately treated and you ask, how long do those migraines last and one last 3-4 days, you're already between 14 to 16 days. So again, the frequency of the abortives, you're absolutely correct is critical. But also the number of headache days and the amount of debilitation because you also got to understand how's the quality of life affected? Are patients missing out on work or social activities or family activities, how is that affected as well? So again, putting that all in context, and that is where we do a phenomenal job at a place like the Cleveland Clinic with our patient related outcome measures and questionnaires because we get a much deeper understanding behind just quantitative assessments.

Glen Stevens, DO, PhD: So Emad, I love having the headache center here, as big as it is. It's great. And you guys do wonderful work and have great access. Seems to be an ever-growing population of people. But any closing remarks? Anything we haven't touched on that you want to bring up to all our audience?

Emad Estemalik, MD: Our physicians, we're always available. We're very ready to help any physician, even outside the Cleveland Clinic with referrals to our center. We pride ourselves with our interdisciplinary approach towards headache management. Glenn, you know how we operate here. There's a lot of interdepartmental interinstitutional collaboration when it comes to disease management as well. So we work closely with other centers in the Neurological institute and outside that as well. You've mentioned sinus headaches and where do our ENT folks come in and of course others as well. So again, I think our model of care is unparalleled when you look at it throughout many other centers. So we're always there to help anyone that needs help.

Glen Stevens, DO, PhD: Well, Emad, our listeners and I appreciate your coming in today telling us the evolving field of migraine management. It's always fascinating to me and I find it seems to be moving so rapidly that it's just hard to keep up on it. So these are great to do and appreciate your spending some time with this on Neuro Pathways. Thank you very much.

Emad Estemalik, MD: Thank you, Glen for having me. Always a pleasure.

Closing: This concludes this episode of Neuro Pathways. You can find additional podcast episodes on our website, clevelandclinic.org/neuropodcast, or subscribe to the podcast on iTunes, Google Play, Spotify, or wherever you get your podcasts. And don't forget, you can access real-time updates from experts in Cleveland Clinic's Neurological Institute on our Consult QD website. That's @CleClinicMD, all one word. And thank you for listening.