Triptans, CGRPs, and Botox: Your Migraine Medication Options Explained

Two Types of Migraine Medications

Interviewer: When looking at migraine medication advice on some parts of the internet, it's things like drink water or ask your doctor about this particular drug. And there's not a whole lot of in between. But when it comes to the broader medical field, migraine treatment is seen more as a toolbox. Some meds stop an attack, some prevent the next one, and some are just to manage some of our symptoms.

Today, to help us make sense of the medications in our toolbox, we're talking with Dr. Karly Pippitt, who sees patients in the Headache Clinic at University of Utah Health.

Now, Dr. Pippitt, let's start with some of the broad categories of medications. If someone is suffering from migraines, what kind of medications can we use to help them out?

Dr. Pippitt: There are two big categories that we think about when treating migraines. The first is acute or rescue medications, so things we use to help you resolve that migraine that's happening right now.

Interviewer: Okay.

Dr. Pippitt: And then the other big category is prevention. So what do we do? Literally what the word says: "to prevent" that, or at least lessen the number of migraine attacks, potentially lessen the intensity of the attacks, or the duration of the migraines. Prevention meds can work on all of those things.

Acute (Rescue) Medications

Interviewer: Where do we usually start when you see a patient who is suffering from migraines?

Dr. Pippitt: So much of this depends on how many migraines you're having. So, what is the burden of migraine that someone is experiencing? So if this is the first time you come in and you're talking to me about your headaches for the first time, we'll probably mostly focus on rescue or acute treatment, see if we can make this diagnosis based on your history, treat those acute moments, see how you respond to the treatment.

Preventive Medications

Now, if you came in and said, "I don't know. I feel like I'm having a headache every single day. It's been this way for a couple of months," we might actually start talking about preventive treatment first.

To start preventive treatment, you don't have to have a headache every day. Ideally, please, be seen before something like that happens.

Interviewer: Sure.

Dr. Pippitt: Typically, we talk about starting preventive treatment when you're having two to four headache days per month. And then we'll think about would something like that would be useful to you to decrease the frequency of migraines that you're having?

Choosing the Right Rescue Medication for Migraines

Interviewer: And for maybe people who have been trying some of the over-the-counter medications, things like ibuprofen, acetaminophen, when it stops working, what is the next kind of step in treatment that they might need to speak with a doctor about?

Dr. Pippitt: I like that you brought up over-the-counter medicines, because often they are effective for people. I think just because they work doesn't mean that this isn't something to talk to your doctor about. But especially when they stop working, that's the time to reach out, because there are some specific migraine medications, especially for rescue, that work better because they are targeted more towards migraine and not just general aches and pains, like things like ibuprofen would be.

Triptans

The first big class of these that came out is called the triptans, and that's because that is the ending of most of their names in the generic form. These medicines have been around since the 1980s. So there are multiple different ones of them that vary in their half-life, that then if someone's having a migraine that lasts more like a couple days, we might choose one that has a longer half-life versus someone who . . . Most migraines are about 24 to 36 hours, so sometimes the first of those triptans that came out will be a little bit more effective.

CGRP Medications

Interviewer: When it comes to triptans, I know they are kind of like the classical rescue medication. But are there any types of people who may not be a good fit for triptans, and maybe we need to start looking at something else?

Dr. Pippitt: Yes, absolutely. Triptans are contraindicated in patients who have a history of cardiovascular disease. So people who have a history of a heart attack or a stroke are not eligible for triptans. And so, luckily, there are some newer medications out on the market that are, again, more migraine-specific, so we don't have to resort to just general pain medications to treat the pain, which is things we had to do in the past. These new medications are called the CGRP antagonists. CGRP stands for calcitonin gene-related peptide.

And we've known that that's a molecule that's implicated in the pain pathway associated with migraine, and has just recently been used as a drug target both for rescue medications and prevention in about the last 20 years or so. So if you have a contraindication to a triptan, then we will automatically jump into something like a CGRP. But I would say, just because the CGRPs are maybe a little more specific, I would still argue that triptans are actually migraine-specific medicine and are the right place to start.

I hate to say cost and insurance coverage come into decision-making, but they do. Newer medications are always a little bit more expensive, and as much as we sometimes all want the newest, brightest, shiniest thing, that doesn't mean that actually . . . I sometimes joke that drugs are like oldies but goodies, right? It's been around for a long time. It works really well. There's no reason not to try it. Insurance typically wants people to have tried and failed at least three triptans before we move on to a CGRP.

Interviewer: Is there anything else we should know about acute treatment?

Dr. Pippitt: So with any migraine, the key to effective treatment is treating early. So as soon as you know this is a migraine or even suspect, as soon as you have that aura symptom, the sooner that you take your rescue medications, the more effective they are.

Managing Migraine Nausea and Alternative Medication Forms

Interviewer: And when you're talking about acute and rescue medications, what about people who maybe can't necessarily take an oral medication?

Dr. Pippitt: Yes. Nausea is a really big deal in migraine, as it is part of the diagnostic criteria for migraine is to have nausea. We know this nausea actually comes from gut stasis, or your gut just not moving things through like it did before. So there's a nausea medicine that we really like to use. It's called metoclopramide because the way that it works is actually a pro-motility agent. So it helps sort of restore that gut stasis that gets slowed during a migraine attack.

When we use this, I will typically have people take that nausea medicine first, and then in about 10 to 15 minutes take their rescue medication. Now no harm in taking them at the same time. You just might get a little bit better efficacy. But if someone says, "Oh, I feel like my rescue medication only works 50% of the time," or like you said, "My nausea is really bad, and I feel like I'm late in taking my medicine until that gets better," these are really great things to think about.

For those people who have kind of passed the point of no return with the nausea, some of the triptans are available as a nasal spray or as an injectable option. So those are there and have a little bit faster onset of action. Sometimes can have a little bit more side effects just because of the way that they're delivered, can irritate the nose, can cause a little bit more flushing, things like that.

When Is It Time to Start Preventive Migraine Medication?

Interviewer: When do we start thinking about prevention versus acute? I know you had mentioned something about frequency, but is it also like severity?

Dr. Pippitt: I would say both really matter. So maybe you only have one migraine a month, but you're down for three days, and you're like down-down, like back to that dark room, huddled in a ball in the fetal position. So this really impacts your day. Some people don't really want to take medicine every day. Some people feel so terrible, they're like, "Oh, please, do anything if it minimizes my chance of that happening more."

Lifestyle Changes That Support Migraine Treatment

I would also say, too, some of this is we can throw all the medications in the world at someone, and if you are not doing the things to take care of yourself, meds can only do so much. So sleep is a really big trigger for people. So being consistent with sleep-wake hours.

Medicine is one of many fields where we're open 24 hours a day. So there are a lot of people who work night shifts, who do shift-changing sort of things like that. That wreaks havoc on many things in your health, including migraines. So just trying to keep as consistent of hours as you can with sleep, staying hydrated, not skipping meals, and getting some regular activity every day are very important just for general treatment of migraines.

So when someone is doing all of those, and you're still having a lot of migraines, and you want to do something, yeah, there are quite a few options for everyday medications. Now, many of these medicines that we use initially, I'll talk about them in broad categories, they are blood pressure drugs, they are anti-seizure drugs, and they are antidepressants. By the very description of each of those, I have not said headache or migraine once.

Interviewer: Sure.

Preventive Medication Options Explained

Dr. Pippitt: These medicines, again, have been around for a long time, back to the oldies but goodies, and have good data to support reducing migraine frequency and intensity. So, typically, we're going to start with some of these oldies but goodies in the category, not only because it's a requirement before we get to some of the newer, more migraine-specific medicines, and there's been some arguments from headache bodies about why we are withholding these more migraine-specific medications from patients? It's because they work. We're not trying to torture people to make them jump through hoops. But if there is a cheaper option that works better or that works, that's still a reasonable choice to make.

So these classes of drugs, like we talked about, the anti-seizure drugs are a big class. And within each of these classes, there are some quintessential drug choices within them. There are actually quite a few blood pressure drug categories that can be effective. The one that has the most data behind them are the beta-blocker drugs. But there is some emerging data for drugs that we might think about more for someone who came in with high blood pressure. So these would be things like the ACE inhibitors or the angiotensin receptor blockers. So many people may come in on these drugs for another indication, and it's nice to let them know, "This might actually be reducing your migraine frequency even though you don't think about it."

Interviewer: Oh, sure.

Dr. Pippitt: Another class of blood pressure drugs is called the calcium channel blockers. The data on these is maybe not as robust for some of the other prevention drugs. But one of my colleagues always likes to say, "These drugs just never really got a good trial to prove that they're helpful."

How Doctors Match Preventive Medications to Your Symptoms

How do you know which class of drugs you want to give someone or what to try? This is where that history matters. So I'm getting back to the calcium channel blockers, I promise. If you came to me and you had migraine with aura, I would often choose a calcium channel blocker because those seem to work very well in people who have migraine with aura. So it is the other conditions, the other things that someone complains about, that help make my decision about what class of drugs to use.

So we've talked about sleep. That's a big issue. If someone says to me, "Oh, I don't sleep very well. I just feel like I wake up all the time," the class of drugs that I like to use a lot is the tricyclic antidepressants. I tell people, "I'm going to use a tricyclic antidepressant." If you came to me and said that you were depressed, this is not the class of drugs I would use. These drugs are beneficial for pain and sleep, and that's what we're using them for.

But I do like to be transparent and let people know, "This is an antidepressant." So I don't want them to think that I'm labeling them with another condition or something else that's going on, so they know the why of what we're doing.

Typically, insurance wants three or four of these categories of drugs before they think about potentially moving on to some of the newer drugs that are out there. So similar to the acute drugs, the first of those calcitonin gene receptor peptide antagonists actually came out in the prevention category. The first three that came out are all monoclonal antibodies. They're injectable medications. So it's a once-a-month injection that people do to help prevent migraine.

We've noticed in clinical practice, although the trial data suggested about a 50% reduction in migraine frequency, often there's also a reduction in intensity. So maybe before you had to take two of your triptans, one, one again in a couple of hours to actually resolve the migraine. Now you might be able to get away with one. Maybe you don't even actually need anything, or maybe just some ibuprofen, because the intensity actually isn't so much that you can actually get through the day.

What to Expect from Migraine Treatment

Interviewer: Got you. I've seen a lot of talk in all sorts of different places about these CGRP meds. There are some celebrities who are talking about them. I mean, it's kind of positioned as "It cured my migraines. I will never have a migraine again." With some of these preventive medications, how do you help set expectations for a patient?

Dr. Pippitt: That is, I think, one of the most important things that we can do is set expectations. I often see people in the Headache Clinic who come in with a decades-long history of headache, and I will often say to them, "You've been through this long enough to know that there is no cure for this. There is no magic wand I can wave or magic medication I can give to you that means you're never going to have a migraine again. Our goal is how do we help that you can still live the life that you can function in the way that you want to, and you have less missed days of life, less missed days of fun, less missed days of work due to your migraines."

And that's really our goal with treatment. As someone who has migraines, yes, I would love for there to be a "cure" and this never happen again, but that's just not the reality.

Botox for Chronic Migraine: Who Is It For?

Interviewer: Got you. And I guess before we kind of wrap things up, I do want to talk about the one other kind of medication that keeps popping up about a potential cure. How about Botox for migraines?

Dr. Pippitt: So Botox is another thing that gets advertised on TV, or, most technically, Botox is the brand name. But a lot easier to say than onabotulinum toxin A, which is a bit of a mouthful.

So Botox is indicated for something we call chronic migraine. And only in the headache land does chronic mean frequency, not duration. So chronic migraine is greater than 15 headache days per month, with over half of them being migraine. Those headaches need to last more than four hours, and that needs to be happening for more than three months. That's the technical definition of chronic migraine.

And then Botox injections themselves, this is a series of about 31 injections, in a very proscribed pattern, over the forehead, top of the head, back of the head, and upper shoulders that's done every 3 months. One thing for me is that Botox treatment is a series of injections three months apart. And when this was first developed about 15 years ago, you had to do 3 rounds of it before you really gave it a thumbs up or a thumbs down.

So for some people, that takes about nine months before you really know, is it working or is it not? One question I get a lot is, "Well, we know that this is a toxin, and we're paralyzing the muscles. You've told me that migraine is a brain disease. So what gives? This doesn't make sense to me, like, are you sure I have migraines if this is what's happening?"

I think this just goes to show you that this is a lot more complex than to just say this is a brain disease. With things like Botox, with things like the new CGRPs, I would not say that either of them is miraculous. They just work very differently than any of the other medications that we have. And so for some people who've suffered for a long time, they may feel like a miracle cure, because they're very different than anything else we've tried before.

Why Migraine Treatment Often Combines Multiple Therapies

And I think another really important part of treatment, especially with prevention, is I often liken it to cooking. So if you're cooking something, it's not just about adding salt. You add a little bit of salt, you add a little bit of pepper, you add a little bit of oregano, you add a little bit of thyme. That's really what makes that beautiful combination. And I would say that's true of preventive medications as well.

You might need a little bit of one medicine to help with sleep. You might need a little bit of other medication that helps with your nausea. And then another medication that's maybe a little bit more specifically targeted towards migraine. But those other two medicines also show benefit in people with migraines. And that's really what's going to make the perfect combination for you.

And I would say this is a big change I made in treating these primarily in primary care, and maybe not change as much as a learning curve that I wouldn't be like, "Oh, we tried this medicine. Maybe it gave you a little bit of relief, but not enough. Stop. Change to something else." Now I would think about like, "Okay, this gave you . . . You have 15% less migraines. Okay, that's a benefit. How can we tweak that more? Do we change the dose of that? Do we add another medicine that works differently but in a more complementary way?" And I think that's an important thing for people to understand: that it may be a combination of things.

And I think also these may not be something you're on for the rest of your life. Patients kind of fall into a couple of categories. If you look at migraine data in people who are taking preventive meds, often at a year or two later, many people aren't taking them anymore. Could that be medication side effects? Sure. Some of it is this is just the natural history of migraines. They get better; they get worse. They ebb and flow throughout life. So there may be times when you want more medications or need more medications, and other times when actually you do pretty good and maybe lifestyle is enough.

If You’ve “Tried Everything,” There Are Still More Options

Interviewer: If you had to give one piece of reassurance to someone who's listening, who has been struggling with headaches and migraines and feels that they've tried "everything," what would you tell them about the kind of medication landscape and what their next steps should be?

Dr. Pippitt: I would say there's always another trick up our sleeve. There's always another option. When I see new patients, I always tell them, "So this is our plan A. I've got a plan B. I've got a plan C. I've got a plan D." So there are always more options. And be willing to try things again. You and I are not the same people that we were 10 years ago. Your body is not the same. So you may not have responded to something in the past. That doesn't mean you won't respond to it now. So be open-minded to that.