Guest: Dr. Risa Ravitz

View the recording from our Migraine Clinician Masterclass, developed in partnership with IVPN Neuropsychiatry. In this webinar, we hear from Dr. Risa Ravitz, who discusses the Patient and Clinician Perspectives on Using Modern Therapies for Migraine. Please note that this video is intended for healthcare providers.

TRANSCRIPT

Dr. Risa Ravitz: So again, I appreciate the introduction. And it is true, I do see a lot of patients specifically for migraine, and it’s been an exciting time with new medications, an exciting time in diagnosis. So, let’s jump right in. So this talk is titled Patient and Clinician Perspectives and the Use of Modern Therapies for Migraine.

So, I think one of the first questions – and always an important question – is to treat or not to treat. We see these patients in various settings, and always that is the question, do we treat or do we not treat? So I wanted to present one or two fictional patients and go over an overview of the medications and the modalities that are available to treat migraine. And it’s a very broad topic, it’s what I do every day, but I just wanted to show you how I go through my thinking about how to treat patients. 

So let’s start with the first fictional patient. So S is a 35-year-old female. She’s been suffering from migraine with aura. She works as a software engineer and gets headaches one to two times a month. She has been using triptans and NSAIDs intermittently with good relief, but she sometimes doesn’t treat the headache and likes to wait it out. So the question always is, first of all, does the patient need treatment? Will she use the treatment – because, as you all know in practice, that’s a challenge as well – and if she’s going to, which treatment is appropriate? 

So here’s a quick summary, and it’s not a completely exhaustive list but a pretty good list of the modern therapies that we have around the world and sort of the most common therapies that we use in the US here. So they’re separated into two different categories, the abortive medications and the preventative medications. And the abortive therapies include the nonsteroidal anti-inflammatories, the triptans, the gepants, ergotamine, butalbital, acetaminophen – forgot to add aspirin on here, that’s also on this list – and then tramadol and opiates and some of the antinausea medicines.

And the common preventative therapies that we tend to use are beta-blockers, calcium channel blockers, anticonvulsants, including valproate, topiramate, carbamazepine’s, anisamide, lamotrigine, and gabapentin. We use the tricyclic antidepressants and other antidepressants, including SSRIs and SNRIs. We have the CGRPs and the mAbs now. We use NMDA receptor antagonists, and we used botulinum toxin therapy. 

Male: One of our audience is asking, what’s the difference between episodic and chronic migraine? 

Ravitz: So the difference between episodic and chronic migraine is that it’s basically the number of times that it occurs, typically in a month, is how we measure it. So, episodic migraine is typically defined as… they change it a little bit, but up to four to eight headaches a month. And now chronic migraine is starting at six to eight headaches a month, and those are headache days, so actual days that the patient is experiencing headache.

And the way that we – I’ll just talk a little off the cuff here – look at it is that we want to treat patients with episodic migraine with abortive medicines. We want them to be able to take the medicine and then get rid of the headache. And we start to think about preventative medications when patients have more than four headaches a month, typically. But if they have two headaches a month that are super debilitating – where they have nausea and vomiting or they miss work three days a month – we start to think about that as a more debilitating condition. 

So back to the patient. So again, a 35-year-old female suffering from migraine with aura.

She gets one or two headaches a month. I would define her…I would classify her as a patient that has episodic migraine. She’s using triptans and NSAIDs intermittently with good relief, but she doesn’t like to treat. So, she does need treatment, and I think it’s really important for us to understand why she needs treatment and also to educate the patient about why she needs treatment. 

So this is something I see all the time in my practice, and I find it very interesting because it’s very relevant to how patients decide how they want to take medicine, and it’s very relevant to how we communicate with patients. So, this is how a lot of times the thinking plays out. So the patient often likes to say, I don’t like to put any medicine in my body. I try to wait it out. Sometimes I can just power through the symptoms, and I’m often afraid of the side effects. 

So as a healthcare professional, medication is a major tool that I have to offer for treatment. And what patients don’t understand, especially in migraine, is when you wait to treat the symptoms, they often get a lot worse. So there is a big cascade of events that happens chemically, electrically, and there’s a lot of inflammation that’s created. And as that happens, it gets harder to treat the headache later on in the course of when it happens, and patients don’t understand that. So for many other things, they really try to wait it out, but for migraine, it’s really important that patients understand that they should take it. 

They shouldn’t wait. They should be very aggressive, and they should take it. And as far as the side effect question, most medications do have side effects, unfortunately. But I always remind patients that is it worse to have side effects or is it worse to have a terrible debilitating headache with downstream effects like nausea, vomiting, fogginess, and dizziness, and that often gets people a little bit more willing to try medication. 

So again, I cannot understate how important it is that we educate patients and tell them that these headaches need to be treated, so they need to hear this often more than once. Often, it’s not until the second or third visit that I actually convince a patient to take a medicine. I do try to explain to them that migraine is a genetic neurovascular disease, and our understanding of it has evolved. I do try to explain central sensitization.

It plays a very big role in migraine pathogenesis. And basically, if you want to dumb it down for patients, migraine can potentially make migraine worse. It can make them more severe and more frequent. So an untreated migraine lasts longer, and frequent migraines are believed to cause more frequent headaches. So the sooner the migraine is treated, the better the outcome typically. So again, I remind the patients are the side effects worse than the migraine? 

So this patient for sure qualifies, in my opinion, for abortive therapy. Again, she sometimes treats the headache, and it sounds like sometimes they’re maybe undertreated. So for me, what I would do is I would offer this patient NSAIDs, triptans, gepants, and Benadryl as tolerated. So what also happens – and this is a longer story – sometimes when patients are taking triptans, the same one for many years at a time, and likely this patient has been taking it for many years, or even a triptan, they start to build a tolerance to it. 

So for example, the sumatriptan 50 mg that they used to take may not work as well as it used to. Or the over-the-counter Motrin 200 mg they were taking doesn’t work as well as it used to. So I would optimize that, and I would rotate, if necessary. There are seven triptans available, at least in the US, so I would rotate it to a different one. Just trick the brain a little bit so it’s not used to it, and it actually will respond. And I often will change the anti-inflammatories as well, and I also offer the new gepants, so it’s a different mechanism of action – we’re going to talk about that as well – this is rimegepant and ubrogepant. I do use diphenhydramine, as needed, sometimes a short course. The antihistamine component of this helps with migraine, actually. So I don’t use it for sleep. I actually use it for the migraine at night. 

Again, I’m reiterating to treat early and aggressively. I’m asking again if the side effects are worse than the headache. I reiterate the cascade of chemical and electrical events that occur when untreated. And I want these patients to have a loose headache diary, so they’re more aware of themselves of how often they’re getting headaches. 

So let’s go through the different abortive therapies briefly. Again, not an exhaustive list of everything about them but just things that I notice that are very helpful in practice. So anti-inflammatories and aspirin the considerations and side effects, the exact mechanism of action is not completely understood. It inhibits cyclooxygenase and reduces prostaglandin and thromboxane synthesis. This is an inflammatory pathway. There is a lot of inflammation that’s created in migraine, a lot of inflammation around patients that have migraine in their menses, and this is a very helpful medicine for migraine. 

I often choose the NSAID based on the half-life of how it works. For example, the Motrin and diclofenac tend to be a little shorter-acting, and I use some of the longer-acting ones to rotate patients, so they get longer relief depending on how long their headaches last. So an effective dose is also very important. These patients often need anti-inflammatory dosing, especially if they’ve been taking this for many years. Again, many, many patients start with like one or two Advil that they’ve been taking, and that just simply doesn’t work anymore. 

Relative contraindications, concurrent peptic ulcer disease, a lot of people don’t tolerate this anymore, and there is a very strong possibility for medication overuse headache. I’m not going to get into detail about this. But medication overuse headache is defined as taking medication more than 3 times a week for over 90 days. And what ends up happening is the patient creates a true tolerance to the medicine.

So the body has receptors, the receptors get filled by the NSAID, there’s upregulation of the receptors, there’s more anti-receptors, and this is true physical tolerance. There is a belief and theory that this actually creates more headaches, so you get withdrawal and you actually get more headaches. So I do not want my patients using this a lot.

I do not want them using it more than once a week, even that is a little bit much. But it’s something to really think about, and you will see patients that come in, and they’re going through a bottle of Advil every month or every two weeks. And again, I try to rotate medicines to trick the brain, so they don’t get as tolerant as they could. 

So triptans consideration and side effects. It works by activating vascular serotonin 5-HT1 receptors. It’s a selective serotonin agonist. The dosing is important for this as well. Many doctors are afraid to start the full dosing on this. And I think using the higher dose to knock the headache out is actually more effective than starting the low dose. 

There are known vasoconstrictive tendencies, and this medicine is contraindicated in patients with ischemic heart disease, cardiovascular disease, uncontrolled hypertension, and pregnancy. So over the age of 60, it’s reasonable, and this is how I practice. I try to get cardiology clearance. I do not use these medicines in the strict contraindicated criteria, though. Side effects for triptans – nausea, pain in chin or chest, fogginess. Those are the most common ones that I see.

So ergotamine side effects and consideration. This is an older medicine, but I know it’s available more widely around the world than in the US. We don’t use this as much. It activates vascular serotonin 5-HT1D receptors and constricts peripheral blood vessels. It’s an older medicine. It’s less well-tolerated. The peripheral vasoconstriction is a problem, and it’s definitely contraindicated in patients with CAD, cerebrovascular disease, uncontrolled hypertension in pregnancy, and peripheral vascular disease as well. Side effects are nausea and vomiting. There’s a new delivery system in the US called Trudhesa. I am using it a little bit. It’s often better for younger patients who failed other treatment. They tend to be the patients that can tolerate this, and it’s okay to use.

So the gepants, these are the new medications. The mechanism of action is by blocking calcitonin gene-related peptide. It includes rimegepant, ubrogepant, atogepant, and zavegepant. The nice thing about these medicines is that there’s no real comorbid medical contraindications. It has shown in studies to not have any, which is very, very helpful. Side effects overall have been nausea, somnolence, constipation, and fatigue. You cannot use this in pregnancy. The availability of the drug around the world is variable. The other thing that’s nice about this class of medications is that no medication overuse potential has been appreciated. 

So barbiturates, tramadol, and opiates. So I know there was a question about this in the chat, and I hope I answered your question. The mechanism of action targets opiate and caffeine receptors. There are other mechanisms of actions that are not as well understood. This is the last choice in my practice. So to answer the question in the chat as well, I do not routinely prescribe this in my practice. Interestingly, these medicines weren’t even shown to be that helpful in actually stopping the migraine.

A lot of people just end up falling asleep, and then the headache naturally goes away. So it’s not really a treatment, but it’s a treatment that’s often given in the ER or by physicians that are not aware of the other treatments that we use for migraines. So I do try to avoid this. These medicines are highly addictive. They definitely contribute to medication overuse headache. So the barbiturates and the Fioricet it’s an old medicine that people use a lot of and very, very addictive and hard to wean. And those headaches are not going to get better until the patients are off of the medicine. So I really don’t use this very much in my practice. 

So the antinausea medicines, these are just a few that are commonly used. Metoclopramide is most commonly used. The mechanism of action is not exactly understood, but it does stimulate upper GI tract motility, which is impaired in migraine. So the motility goes down when there’s a migraine, whatever’s in the stomach, the patient throws up. This helps with restoring that downstream side effect, and it also helps with absorption of the other medicines. So it’s very helpful.

We use ondansetron a fair bit. This acts centrally in the brain, antagonizing serotonin 5-HT3 receptors. It’s strong and effective. We use chlorpromazine a little bit. Selectively antagonizes D2 receptors but has some potential anticholinergic effects. So I don’t use it as much, but it is a good medicine. So I’m always considering the delivery and aid to the absorption of the abortives. The ondansetron comes in a melt, so for some patients, that’s better because they’re vomiting and they actually do get some absorption. 

So back to patient S, again, 35-year-old, episodic migraine, getting some relief but maybe undertreating her headaches. Again, I would consider a rotation of triptans and NSAIDs, so she gets a highly effective dose and a dose that just gets rid of the headache. I would start a gepants as an option, reiterating nonuse of the medication in pregnancy.

I would treat and reiterate doing so early and aggressively and just keep considering the mechanisms of action and try to rotate, so you’re not using the same mechanism of action every time. I would discuss medication overuse headache and warn her about it, so she knows if she’s starting to get four, five, six headaches a month, I want to know about that. And give her a headache diary to assess the need for prevention.

So let’s go to the second patient, and we’ll talk about prevention. So to treat or not to treat, patient B is a 62-year-old male with controlled hypertension whose migraines have been more frequent over the last year. He’s getting five to six headaches a month that he treats ineffectively with over-the-counter medications. He’s taking amlodipine. So for sure, the answer is yes to treat. This patient is using over-the-counter medications, which he’s probably overusing at this point, and he has some comorbid medical conditions that we need to consider. 

So again, what each side thinks. I want everyone to start thinking about that. So this patient says I don’t want to have to take any more medicine. I already take medicine for my blood pressure and everything else. And I will have to take medicines for a long time,  and I don’t want to. So I’m almost thinking and saying to these patients, the headaches are going to be hard to control on just abortives alone, and medication overuse headache is probably happening here. So I have that discussion with them.

I also always tell most all of my patients that forever is a long time, and I only try to people on prevention for a few months or a limited time to get things under control, to try to quiet down all the abnormal signaling and excitation that’s happening in the brain. 

So it’s a very similar concept to abortive therapy. Migraines make migraines given the central feedback signaling problem. There’s increased excitatory signaling in chronic migraine. With central sensitization, there’s increased allodynia as well. The purpose and goal of preventative therapy is to make headaches less severe and less frequent. 

That should be the priority, and this is especially true in likely medication overuse headaches. Given the disability and quality of migraines, even less frequent headaches should be considered for treatment. So I even start to consider prevention in patients that have two to four headaches a month that they’re out of work or they’re vomiting and they can’t function. So I want people to know that. 

Okay, so back to patient B, 62, controlled hypertension, on amlodipine, taking over-the-counters with five to six headaches a month. He adds that he has trouble sleeping. So, he needs a preventative medicine. The considerations are age, comorbid conditions such as hypertension, and now I think about his sleep issues. So if we can find a medication that will kill two birds with one stone, we’re going to try to do that. 

So I’m going to go quickly through the preventative medications, and we’ll get back to the patient. So beta-blockers non-selectively antagonized beta-1 and beta-2 adrenergic receptors. The side effects include fatigue, decreased heart rate, impotence, and heart block. I do consider these patients for use that have elevated blood pressure, anxiety, and then I have to consider their age and sex as well. These are effective medications that can really help migraine. And the overall thought about how it works is sort of anti-excitation.

Similar story for the calcium channel blockers. They inhibit calcium ion influx into vascular smooth muscle and myocardium. Again, thought to be anti-excitatory on blood vessel channels. Tends not to lower the blood pressure and heart rate like the beta-blockers. This is used off-label a lot for vestibular migraine. It seems to work very well. Side effects most commonly are constipation and just consider other risk factors such as heart block and comorbid conditions. 

So anticonvulsants consideration. This is not an exhaustive list, but includes topiramate, lamotrigine, anisamide, gabapentin, carbamazepine, and valproic acid. Unclear mechanisms of action but tend to be anti-excitatory as well. Works on sodium and calcium channels in the brain. Side effects that we worry about – metabolic acidosis, dizziness, fatigue, kidney stones. Glaucoma is on that list as well, which I didn’t put on here, and often requires more monitoring than the other medications.

So just a few tidbits about these as well. Topiramate causes weight loss. Patients are always considering a side effect as weight loss or weight gain. Valproic acid can cause LFT elevations and strongly contraindicated in pregnancy. We don’t tend to use that as much here anymore; I don’t in my practice. Gabapentin can help with sleep, and lamotrigine is actually a good mood stabilizer. 

Tricyclic antidepressant considerations inhibit norepinephrine and serotonin reuptake. Side effects include fatigue and dry mouth and weight gain at higher doses. This medicine may help with sleep and anxiety, and you have to consider pure prolongation at higher doses.

The antidepressants, SSRIs and SNRIs, they selectively inhibit serotonin and norepinephrine reuptake. There’s likely a more complex story in the mechanism of action in migraine. Actually, the SNRIs are indicated. The SSRIs are sort of second- and third-line therapy, but they do tend to work as well. This can help with comorbid anxiety and depression. The common side effects are typically GI. This medicine usually needs to be tapered off in their side effects as patients come off, and some patients can have a paradoxical worsening of mood. 

All right, so the new medicines, the CGRP antagonists, considerations and side effects – we have atogepant, rimegepant, and the mAbs, including erenumab, eptinezumab, and fremanezumab. The mechanism of action it inhibits the CGRP release in the CNS and trigeminal nerve ganglion. There are different formulations. The mAbs are injections. They’re once a month. The pills are Nurtec and the Qulipta.

Again, availability is an issue for this around the world. Side effects include fatigue, somnolence, constipation, and local skin reaction. Atogepant has been shown to have statistically significant weight loss. And one of the positive things about this is that there’s no real medical contraindications, which is very helpful.

So memantine considerations used kind of less often but can be helpful. The mechanism of action is to block NMDA receptors. This is excitatory. There may be some glutamate contribution in this as well in the brain. It’s anti-excitatory. Generally well tolerated, and I often use this as a second-line therapy and layering of medication when I use it. Side effects most commonly vivid dreams and also needs to be tapered to discharge, to DC. 

So botulinum toxin consideration and side effects. The mechanism of action is complicated and not completely understood but likely works in muscle relaxation but also probably really works by blocking pain signaling centrally in the brain. So this medication requires injection by a qualified professional every three months. The side effects that are common are headache and actual potential for weakness. The availability is always an issue.

It is expensive. Some of the other medications are expensive as well, but it’s a known availability issue. So there’s also limited contraindications to other medical comorbidities, typically just myasthenia gravis, but generally very well-tolerated, well-studied on many, many, many patients, millions of patients.

So let’s get back to patient B again, 62-year-old male, hypertension, five to six headaches a month, likely medication overuse headache. The headaches, he also says, are increasingly causing disruption in his activities of daily living and he has trouble staying asleep.

So considerations – this patient definitely needs a medication for prevention. I like to reiterate that the medication will not be forever, and I also like to tell him, this is a medicine you’re going to take every day. It will hopefully reduce the frequency and severity of the headaches.

And he’s already taking over-the-counter medications, which typically include NSAIDs, which can lead to peptic ulcer disease and are not great for someone with uncontrolled hypertension as well. I like to reiterate that it will help to reset some of the excitation in the brain, cool things off. He’ll have less headaches. When he has to treat his existing headaches, it will be easier and less debilitating. It will be more effective, and they will not interfere with his life as much. 

So again, discussing and reiterating that we need to do prevention. Forever is a long time. We can stop things at any time. I don’t like these patients to believe that things are set in stone. I do like to discuss that trial and error is probably needed. A lot of times we have to start one thing, and it doesn’t work, and we have to stop it and try something else. Patients can get frustrated with that. 

And again, discuss the various options with him. So given his male sex and the side effects of impotence, I’m going to avoid beta-blockers with him. He’s already on blood pressure medicine, so I’m not going to particularly add another medicine. In contrast, there are some patients that have uncontrolled hypertension that I speak with their primary care or their cardiologist, and we decide to do a beta-blocker or calcium channel blocker. 

So sleep is an issue for this patient. We landed on gabapentin after a discussion because gabapentin has a low side effect profile. It’s good for migraine. We can use low dose and titrate up, and it will probably help him stay asleep. Another consideration would have been the tricyclic antidepressants, but there’s no right answer here. So we try one thing and then go to the next. 

Next, we wanted to address the abortive use with this patient, reiterated getting off over-the-counters, and gave him a trial of gepants given that he has comorbid cardiovascular disease, and gepants would be a good thing.

One, because his body’s not used to this mechanism of action. It will not cause medication overuse headache, and he’s not a very good candidate for triptans, and even NSAIDs. If you’re overusing NSAIDs, again, he can get peptic ulcer disease, worsening hypertension, and medication overuse headaches. So the gepants are a better choice for him and safe in his conditions. 

So nonpharmacological strategies for migraine, just want to do this very quickly because patients are always asking about this. They don’t want to take medicine, even though we have all these treatments that are available, even after this talk about how it’s necessary. There are other things we can do to help them. So just wanted to do some of the evidence-based supplements and some of the other things available.

I tend to use magnesium glycinate or taurate. These were evidence-based and studied at 400 mg a day. Mechanism of action, it likely helps to reduce excitation in the CNS. There was a theory that migraineurs had low levels of magnesium in the CNS. It’s sort of been debunked, that theory, and hard to sort of measure, but it may help to reduce cortical spreading depression, and we think that that’s how it sometimes helps with migraine. 

The glycinate and taurate formulations tend to be easier on the stomach, in general. A lot of the ones that are available, the oxides and the sulfates, either cause constipation or diarrhea, so I like to get them these other formulations that are easier. This supplement is safe in pregnancy. It’s widely available and it’s relatively inexpensive. Side effects are constipation or diarrhea, depending on the formulation. 

So vitamin B2 is another one. It’s also 400 mg a day. It’s overall well tolerated. Mechanism of action not so well understood. Sometimes it can cause flushing, and it is evidence-based that there is evidence to support this for migraine in particular. 

Butterbur also evidence-based for prevention and inhibits L-type voltage-gated calcium channels, 50 to 150 mg a day. This tends to be more expensive. And important to tell patients to buy brands free of alkaloids and other plant carcinogens that actually have been shown to lead to hepatotoxicity. The alkaloids are the problem there. Contraindicated in patients using anticholinergic medicines and not approved for use in pregnancy, so a few limitations with this one as well.

So I get patients often asking me about neuromodulation devices. This is not an exhaustive list but probably the most common questions that I get or that I use in my practice. We have remote electrical neuromodulation, Nerivio; noninvasive vagus nerve stimulation, gammaCore; the external trigeminal nerve stimulator, Cefaly; and the transcranial magnetic stimulation, the SAVI Dual. There’s another one, combined occipital and trigeminal nerve stimulation, Relivion. 

So the mechanism of action for each of these is neuromodulation by electrical impulses set to alter the pain processing in different nerve structures, including the vagus nerve, the sphenopalatine ganglion, and the trigeminal nerve.

There is evidence in pain management for this and also evidence now in migraine. It’s well-tolerated and safe. The cost and availability is variable. And in the States, you actually need to have a prescription to get this medication. They have preventative and episodic indications, safe and well-tolerated. Again, I sort of tell patients that they can try this if they’d like to. Some people have good results from this. Some people it feels like it’s kicking the can down the road, but they still like to use it. 

So, lifestyle changes – I think this is one of the last slides – I always like to go over this with my patients. It’s important. And these are some of the evidence-based lifestyle changes that can help with patients. So I always tell patients to have regular sleep, same time to bed every night, same time up every morning. It doesn’t have to be exact but as much as possible. I have patients that get migraines on the weekends because they sleep late.

That’s the problem. Sleep is a big, migraine trigger. Water doesn’t have to be super crazy but 50 to 60 ounces a day. Meals – I tell patients to have regular meals without fasting. That’s a big reason to have headache. And in a migraine patient, it can often trigger a migraine. Caffeine, for my migraine patients, I usually tell patients one cup to less than one a day. More than that, and you can start to get withdrawal from caffeine. And just like a migraine overuse headache, you can actually get headaches from caffeine withdrawal, and then you get bad migraines. 

As far as food everyone is always asking about food. In the evidence, MSG, tannins, and sulfates were the biggest sort of problematic chemicals for migraine. I encourage all my patients to do a moderate cardio three to four times a week. Biofeedback has been shown to help. And then I do encourage meditation/acupuncture, but there’s less evidence for those. 

So again, just to summarize, overall, listen to patients and try to be heard as well. This is a communication, and we are providing education to these patients, which we have to always remember. Patients don’t necessarily just want to be thrown medicine. They want to understand what’s going on.

And once they do understand these concepts, they are more willing to take medicine, which is better for their overall health. Again, education, education, education. They don’t understand the need to treat.

They don’t understand or have expectation about the trial and error of medication use, and they forget what it feels like to be normal. I can’t tell you how many of my patients have just been living with migraines for a long time, and then we start to get them under control, and they’re like, oh my gosh, I feel better. I feel normal, and I haven’t felt like this in a long time.

So just have your radars out about that. 

So there’s a lot more treatment options now for migraine. It’s a very highly recognized disease now, and the burden in the world is very high. Always consider comorbidities and try to take care of multiple problems with one medication.

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