#406 ‒ Migraine, cluster headache, and tension headache: symptoms, causes, prevention, and treatment | Brian Grosberg, M.D.

“The reason why that's important is when people experience this aladenia, if they use certain migraine-specific treatments like Triptans, but they wait too long, those treatments may be less effective.”

“Those studies ended up leading to the development of Triptans. So estrogen has a number of different roles to play in the pain pathways. Has the experiment been done where you take susceptible women and you selectively give estrogen during the period of time in anticipation of that?”

“That could be NSAIDs and acetaminophen, nosteroidal anti-inflammatory, simple analgesics. It could even be Triptans, migraine-specific medications. It could be barbitri-containing combination analgesics medications like fioracetophioranol, opioids. And then if somebody has other pain disorders, obesity is a risk factor for more frequent migraine.”

“In terms of migraine-specific medications, Triptans were the first class that was specifically designed for the acute treatment of migraine. What predated that were the agotamines, which are still used.”

“And so Triptans, the advent of them really ended up was a game changer for migraine. And even now... 20, what, 30 years ago? We're probably going back to the 1990s.”

“It's also available in nasal spray. And then since that time, there are six more that came along. So there are seven Triptans in total. Are these drugs like statins or GLP-1 agonists, where each new version gets more effective and has fewer side effects?”

“Not necessarily. So there are plenty of people. Sumitriptan was the first one. Some people may be sensitive to sumitriptan versus some of the later Triptans. One of the potential side effects of Triptans is a sense of warmth or heat or tightness anywhere in the body.”

“And then other people use sumitriptan, no issues whatsoever, right? Like, God made this for me. Some of the half-lives of the Triptans may be different. So there may be some that are quicker onset, some that may last longer. And so that's where the decision-making may come in.”

“Okay. Success rate for these across all comers? So looking at Triptans, or for any acute treatment, I'm looking at speed of onset, improvement in associated symptoms, functionality, which is very, very important. Generally, the mark of time that's used is by two hours.”

“And certain Triptans may have a higher recurrence than others. And so that's where the decision-making is used based on all the factors that patients tell me about.”

“in migraine therapy, including CGRP-targeted medications, neuromodulation devices, and even Botox, and when headaches may signal a secondary, more serious underlying condition.”

“I mean, it's just short-sighted, I think. Rounding out this list, calcium channel blockers and Botox, correct? Yeah. Yeah, let's talk a little bit about those two. So calcium channel blockers doesn't have as much data for prevention of migraine.”

“Right. Nothing comes without a side effect, but the side effect can often be well worth it. And then you mentioned Botox. Botox. See, when I think about Botox, I think about tension headaches, but does it also play a role in migraines and clusters? Surprisingly, Botox doesn't work well for tension type headache.”

“So that's where we're by people experiencing 15 to more days of headache per month. That's where Botox has mostly been studied and where it has the current FDA approval for that. And so it's not by cosmetic effects that it works, but actually it interferes with the release of certain SNER and SNAP proteins, certain proteins, and also involvement in CGRP, calcitonin gene-related peptide.”

“Because this would be even more expensive than monoclonal antibodies. I mean, Botox must be insanely expensive. So not necessarily relative to the monoclonal antibodies because the monoclonal antibodies.”

“preventive therapies and either try and fail or been poorly intolerant to them before they let me end up looking at Botox for prevention and chronic migraine. Got it. Okay, so let's talk about the rescue drugs.”

“And so there was like that aha moment. And that's what led to the class of what are known as CGRP antagonists. And the CGRP antagonists are kind of broken down into two buckets. One are what are called large monoclonal antibodies, which is the medication that our patient was placed on.”

“These are drugs that are administered intravenously at what frequency? The CGRP antagonists, the large monoclonal antibodies, three of them are self-injection medications, almost like EpiPens. And those medications have a long half-life.”

“Super interesting. You mentioned the oral equivalent of these as well. Yes. So there are oral medications that are known as GPANs that are small molecule CGRP antagonists. These medications have shorter half-lives and there are fewer of them.”

“Once again, that's in the class that we were talking about, that CGRP antagonist. Those bioavailabilities are higher. And so that's where somebody may end up getting faster relief.”

“Do opioids play any role here? Notwithstanding the loaded nature of addiction and things like that or dependency? We go back to the risk factors for migraine chronification, and one of the risk factors is medication overuse.”

“is even banned in some countries in the world. Opioids or this class of medications, the barbitric-containing combination analgesics, even used a handful of times per month, even if it's not for migraine. The nervous system, once again, may not like that, and they have a particularly high risk for medication overuse.”

“You have enough other tools that you're not going to do that. Once again, opioids, for me, are a last line. After people have explored everything, if you will, even in the emergency room, we really try to stay away from opioids just because of this potential.”

“over an extended period of time, that can actually create more frequent headaches. It doesn't happen for everybody. That could be NSAIDs and acetaminophen, nosteroidal anti-inflammatory, simple analgesics. It could even be Triptans, migraine-specific medications. It could be barbitri-containing combination analgesics medications like fioracetophioranol, opioids.”

“Non-migraine-specific, so analgesics like acetaminophen, non-steroidal anti-inflammatory drugs like NSAIDs. Do opioids play any role here? Notwithstanding the loaded nature of addiction and things like that or dependency?”

“USMLE studying. Is that still used? Yeah. Okay. Beta blockers are a class of blood pressure medications. The exact mechanism how they work isn't known. It's postulated that it may have effects on the sympathetic aspect of the nervous system. And so two of the beta blockers that are FDA approved are propranolol and timolol, but there are other beta blockers that are used as well.”

“but there are other beta blockers that are used as well. They can be very effective for people. Once again, there's... Quotient if somebody has asthma. So there are different types of beta blockers. So it can potentially exacerbate asthma. Potential side effects include lowering of blood pressure or heart rate or exercise intolerance.”

“I mean, it's just short-sighted, I think. Rounding out this list, calcium channel blockers and Botox, correct? Yeah. Yeah, let's talk a little bit about those two. So calcium channel blockers doesn't have as much data for prevention of migraine.”

“More classically, it's used for prevention of a headache like cluster headache. But still, people may end up using calcium channel blockers, which is a blood pressure medication for prevention of migraine. And they're doing this at a lower dose, I'm assuming, as well? A lower dose, but sometimes the doses are increased, particularly in patients with cluster headache.”

“I'm surprised that we don't also see that post ovulation because you also have a very sharp decline in estradiol post ovulation. They kind of have two. They're sharp. They're not as sharp at the end of ovulation and then not as sharp at the end of the luteal phase. Did they see anything mid-cycle?”

“In other words, we ended up having to use estradiol and progesterone, as you do in perimenopausal women, but less than you would normally have treated someone. In other words, we couldn't take her to full therapeutic dose. Is that common in menopausal women?”

“Yeah. Yeah. Is that GABA-related? What do we think is the pathway there? I think it depends. The anti-seizure medications, too, that are FDA approved are tapiramate, which is known as Topamax, and valproic acid, known as Depakote. These medications have different mechanisms of action.”

“That can be very effective for people, but it does have, like every other medication, potential side effects. And then valproic acid or Depakote, once again, can have effects on GABA as well. That medication also may be helpful, but also has potential side effects. And it's really important that we go back to the patient population where I have migraine, so I'm not only sympathetic, but”

“A lower dose, but sometimes the doses are increased, particularly in patients with cluster headache. So what do you do if you have a normotensive person with cluster headaches? How do you treat them with verapamil? There are some patients that I have where usually in collaboration with a cardiologist.”

“milligrams of verapamil. And for your audience to know, that is an exceedingly high dose. Once again, EKGs need to be checked, blood pressure, pulse needs to be checked, tolerability needs to be checked. But that was the dose that was needed, and that person tolerated it amazingly.”

“our belief? Yes. Okay. And then what about on the anti-epileptic side? Talk about getting a patient anxious, right? It's like, we're going to give you a drug for epilepsy. Yeah. Yeah. Is that GABA related? What do we think is the pathway there?”

“the drug. That's okay. That's okay. That is for preventive treatment. That's not one that you can use acutely. No, that would not be used acutely. Remedgepant, or what's known as Nurtec, has an indication for preventive and acute treatment. Gubrogepant or Ubrelvi, which is another medication in that class, has an FDA approval for acute treatment of migraine.”

“So meaning they were increased during migraine, and then the use of sumatriptan would end up normalizing levels. And so there was like that aha moment. And that's what led to the class of what are known as CGRP antagonists.”

“It's postulated that it may have effects on the sympathetic aspect of the nervous system. And so two of the beta blockers that are FDA approved are propranolol and timolol, but there are other beta blockers that are used as well. They can be very effective for people.”

“Yeah. Yeah. Is that GABA-related? What do we think is the pathway there? I think it depends. The anti-seizure medications, too, that are FDA approved are topiramate, which is known as Topamax, and valproic acid, known as Depacote. These medications have different mechanisms of action.”

“If a person has a tension headache and they take a thousand milligrams of Tylenol and they get better, do they have a tension headache? Or in other words, could it respond to something as simple and over-the-counter as that?”

“Rimegepant or what's known as Nurtec has an indication for preventive and acute treatment. Goobrojapant or Ubrelvi, which is another medication in that class, has an FDA approval for acute treatment of migraine. Got it. Do you have a sense, by the way, what the out-of-pocket cost on these drugs is?”