Narrator:
0:01
Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts, powered by ENCORE Research Group and hosted by cardiologist and top medical researcher, Dr. Michael Koren.
Dr. Michael Koren:
0:17
Hello, I'm Dr. Michael Koren and I'm moderating another session of MedEvidence with Dr. Steven Toenjes, who is a fabulous neurologist. This is our second discussion about headaches in general and migraines specifically, and we had a fabulous conversation just now about the epidemiology of migraines, about the things that causes migraines, the different types of migraines and some really interesting cases about triggers for migraine. I was especially fascinated about the teacher who had a migraine reaction to smell to the extent that they couldn't do their profession anymore because they became aphasic, meaning they couldn't speak if the migraine was triggered by that smell.
Narrator:
1:01
Isn't that crazy?
Dr. Michael Koren:
1:02
And it was perfume, if I remember correctly, it was yeah. So migraines can have many type of manifestations and they're the second most disabling thing for our general patient population. So pretty interesting stuff. So let's get now into the treatment of migraines, and obviously you're our expert on it, so kind of run us through the gamut you mentioned some things in the first session but kind of break it down for people from non-pharmacological things, first line, second line, prevention versus acute treatment.
Dr. Steven Toenjes:
1:38
First understand that the goals of treatment and I do believe it should be viewed in this manner both from the provider and the patient is that what we're trying to do with treatments is mitigate that disability. We're trying to mitigate the person's you know, trouble they're having functioning at work in their personal lives, and that's a good thing to try to do.
Dr. Michael Koren:
2:08
So just before we get into that, out of curiosity as a neurologist, do people come to you directly? Are you getting more referrals for people that have failed other things and have preconceived notions about what works and what doesn't work?
Dr. Steven Toenjes:
2:19
It's a mix. It's absolutely a mix. We see it all for sure. So just in general, we mentioned in the last session some behavioral approaches. Those are always important to make sure that a migraineur is pursuing.
Dr. Steven Toenjes:
2:40
But in terms of medication options you know we do I think it's helpful to split medications really more into three categories. We'll say acute or abortive therapy. Those are medications that you're going to take when you have a headache and you're trying to abort that headache. One of our very important categories of treatments is preventive therapy. These are therapies that we have either sustained exposures to or daily therapies, and they have as their goal reducing the frequency and overall severity of the headache syndrome.
Dr. Steven Toenjes:
3:20
I include a third category where we really use the term rescue therapy. Oftentimes rescue will be used to describe abortive therapies, but in our clinic our rescue therapies are really you know, keep me out of the emergency room therapies. I've got an extremely severe headache and you know the person may just be profusely vomiting up everything that we're trying to give to them at that point, and so something to sort of end that when things have gotten a little too far. You know I keep that sort of as a special category on its own. And so our patients. We do differentiate abortive therapy and rescue therapies. It's very helpful with, just in a general sense. When we're talking about success with various therapies. What do we mean by success?
Dr. Steven Toenjes:
4:22
If we're talking about abortive therapies, we mean that the person gets relief from the abortive therapy meaning in the goals and an acceptable goal is within a relatively short period of time.
Dr. Steven Toenjes:
4:36
Within a yeah hour or two to get to either no pain that's the best obviously and then remain pain-free, sustain pain freedom or minimal pain, so mild or no pain, and then without significant side effects. Through the years, you know, patients will often report that a medication works very well for them, but the medication also produces some disability, ie sedation, and then the person is out of commission because they're basically put to sleep by the medicine that they're taking. And so what we really mean by success is, the vast majority of the time with an abortive therapy, pain-free or minimal to no pain, and the person is returning to function, not having to sleep for the rest of the day. Gotcha Preventive therapies we usually will set as a goal at least a 50% reduction in frequency. That often comes with a reduction in overall severity, and so that's kind of how we define what we mean by success tolerating a therapy either no or minimal side effects and then also achieving the 50% reduction.
Dr. Michael Koren:
5:58
So just Is that something achievable for most patients, or can you get to zero or give us a little bit of sense for where we are in terms of current therapies?
Dr. Steven Toenjes:
6:07
Sure, speaking specifically about preventive therapies, we break them up into our conventional oral therapies that we've had for a number of years. Really, when we say that, we're referring to several specific medicines beta blocker, blood pressure medicines and some other blood pressure medicines like verapamil and other calcium channel blockers. Seizure medicines mainly topiramate, although there are others and then medicines in the antidepressant class, mainly the tricyclic antidepressants like amitriptyline or Elavil, although SNRIs like venlafaxine also do have some efficacy. There are other oral conventional therapies as well, but those are sort of the main three categories.
Dr. Michael Koren:
7:02
For prevention?
Dr. Steven Toenjes:
7:03
For prevention. Well, if you look at and you're seeing, say, a chronic migraine patient in clinic and you grab from either one of those three categories, the likelihood that you'll get success with what you grab is in the range of around 30%, and so most people are not going to either tolerate the therapy or be successful.
Dr. Michael Koren:
7:31
So even just for my knowledge, so even the simpler things that are non-prescription treatments like aspirin or caffeine, do they have preventative effects or they just use for abortive reasons?
Dr. Steven Toenjes:
7:44
So caffeine should be viewed as an abortive therapy. It's not going to be a preventive therapy and it's an important one to understand. It is often very successful at aborting a migraine.
Dr. Steven Toenjes:
7:58
If you look at any over-the-counter formulation and it says migraine formulation on it the thing that's in there that's been added is caffeine, for a reason, but most abortive approaches we have to understand can backfire on a migraine patient. Most abortive therapies, if they are taken too frequently, will actually do the opposite of a preventive therapy and will increase the frequency and severity of the headache syndrome, and caffeine will definitely do that.
Dr. Steven Toenjes:
8:29
So will aspirin. Most abortive therapies will do that. We do have abortive approaches that do not produce medication overuse, headache or rebound phenomenon. Some of our newer medicines in the GPANT class, medicines like Eptinezumap or Vyepti, Rimegepant, which is Nurtec that people see commercials for there's also a nasal spray named Zavzpret that's in the GPANT class. These medicines blur the distinction between preventive and abortive therapy. They are effective as abortive agents and they don't cause medication overuse, and so if taken frequently they don't backfire and produce a rebound phenomenon. They actually do the opposite. They're effective in prevention, and so that's why the Nurtec commercials mention this therapy can relieve and prevent migraines, and the FDA lets them say that in the commercial because it does have efficacy.
Dr. Michael Koren:
9:29
Dual role, dual role. W hereas a beta blocker is not going to work for an acute migraine.
Dr. Steven Toenjes:
9:34
That would be unusual there are. The only scenario that I can think of is there are some beta blocker eye drops that lower intraocular pressure, that actually have a couple of studies demonstrating some efficacy in abortive relief.
Narrator:
9:56
Really.
Dr. Steven Toenjes:
9:57
And so, but for the most part no.
Dr. Steven Toenjes:
10:01
And so now in the migraine world, there's really been two major, really advanced or really explosions in therapies of just a tremendous expansion in what's available.
Dr. Steven Toenjes:
10:17
In the 1990s, with the first FDA approval of sumatriptan or Imitrex there are seven triptans they're all seven generic now. That happened through the 90s and 2000s, and then in 2018, was the first FDA approval of our CGRP-based therapies, or therapies that are directed at impacting calcitonin gene-related peptide signaling within our brain, with the approval of Aimovig in 2018, and then several other CGRP-based therapies that followed shortly thereafter and are in widespread use now. If you look at the success rate that success rate as we defined it and you look at our CGRP-based therapies, you look at our CGRP-based therapies, you'll find numbers more like 50, 60 in some studies getting as good as 70% success. And so it's nice to be able to take patients who feel defeated, feel as though they have lost hope, feel as though that they have attempted so many things throughout their life, and point out to them that since the advent of our CGRP-based therapies in 2018, now we have therapies that most people get to success as we have defined it.
Dr. Michael Koren:
11:46
And we have been part of that clinical trial experience. I know that you've been involved in these studies. We'll talk more specifically about clinical trials in our next segment. That you've been involved in these studies We'll talk more specifically about clinical trials in our next segment. But it's satisfying when you see a concept that started in its infancy, that was developed in clinical trials and now is something that you can tell your patients works up to 70% of the time. That's pretty cool.
Dr. Steven Toenjes:
12:03
You mentioned, can I have no headaches? It is the CGRP-based class that we do. It's kind of a marketing thing. I think that does get pulled out of research trials. But a number of the therapies do have patients that can get a whole month where they actually don't have a migraine. Most people are not going to achieve migraine freedom, but the name of the game is to try to reduce frequency as much as possible and really to try to get the frequency down to where abortive medications are not being used, with a frequency that may be capable of building rebound and really trying to mitigate the migraines that they do get. And so if somebody still has one or two migraines in a week but they can be successful with an abortive agent that we find for them, then you've really started to impact the headache related disability at that point.
Dr. Michael Koren:
13:15
And you mentioned the triptans, which are now generic and less expensive. How do they fit in terms of efficacy between those and the first class of beta blockers and amitriptyline-type class?
Dr. Steven Toenjes:
13:23
So triptans are abortive and the beta blockers are preventive. You know we are in, I think, an evolution of behavior over the last, you know, six or seven years. What we used to have mainly was largely triptans and its parent compound, dihydroergotamine, and NSAIDs and nausea medicines. We always need to remember nausea is very important to treat in a migraine patient and the neuroleptic antiemetics are often capable of aborting the migraine, not just the nausea. And so through the Neuroleptic, meaning a seizure medication, no, no, no. The neuroleptic antiemetics like Promethazine, Phenergan.
Dr. Steven Toenjes:
14:11
Compazine, Reglan, metoclopramide as opposed to Ondansetron, which is not in a neuroleptic category.
Dr. Steven Toenjes:
14:20
So while mainly what we have been trying to treat migraines with abortively is triptans, we've essentially kind of been shoving these things down patients' throats for the last 20, 30 years, including patients who have significant sedation with or other side effects from triptans, and with the invention of the GPANT class, which tend to be very, very well tolerated, you know, we're sort of, I think, and I myself have even noticed that you know you really got to talk to patients about what happens when they use a medicine that they are saying works for them, because some of our newer medicines just seem to be so much better tolerated that they may be capable of getting the same response that they're getting, but not the sedation or other side effects that they've just been accepting as being better than having the headache.
Dr. Steven Toenjes:
15:22
And so you know, I think, that triptans are amazing medicines and for many, many patients probably in the range of a third or so are going to do very well with a triptan, and while they're generic, we often will start with those, unless there are reasons to not use them for sure.
Dr. Michael Koren:
15:42
Interesting, Interesting so, and there's a lot of new things that we're starting to contemplate that are either a progression from previous knowledge or something that's brand new, and we'd like to discuss that in some of the clinical trials that are ongoing and where the gaps are in our next segment. But thank you for that fabulous run through the pharmacology. It gets a little bit complicated, it does, but you're allowed to go back to the beginning of the talk and listen to it again.
Dr. Steven Toenjes:
16:09
Yes.
Dr. Michael Koren:
16:09
And realize that polypharmacy in this area is probably something that you use frequently. Often it's not just one product. It may require several.
Dr. Steven Toenjes:
16:19
And I would point out that I'm kind of skimming the surface here, like we're not really diving into this. There are therapies that I haven't even mentioned, you know, like Botox. We haven't. We'll get there Now, I mentioned it, yes and so, but there are a number of things that haven't even been mentioned and it is sort of a surface view of headache medicine, I think.
Dr. Michael Koren:
16:42
And just the last thing in terms of the polypharmacy elements, do you always build from the first class or is it OK to just jump to the more advanced recent therapies?
Dr. Steven Toenjes:
16:53
So it is welcome that the American Headache Society has changed their stance on the CGRP-based therapies, particularly preventive therapies, and have pointed out that they are medically appropriate first line, for mainly the reasons that we've mentioned. The difference in likelihood of success. Most of the time how we behave or what we can do in clinic is certainly influenced by the overlay of insurance payers, and insurance payers generally require starting with the oldies, but goodies that are also cheapies, right, right. And so variable requirements dependent on certain medicines, whether there's one treatment that needed to be pursued with a conventional therapy, oral or two or three, and different plans have different rules.
Dr. Michael Koren:
17:49
Is that a big problem with insurance? I know in cardiology I deal with it all the time, but I don't know if that was as big of an issue in the headache world.
Dr. Steven Toenjes:
17:57
It's an extremely severe problem. It's a headache. It's a headache, yes.
Dr. Michael Koren:
18:01
Well, with that we're going to end this session of MedEvidence and we're going to jump into some of the things people should look forward to, and also opportunities for people to get involved in clinical research. If they're still struggling with headaches.
Narrator:
18:16
Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidence. com or subscribe to our podcast on your favorite podcast platform.
