Trudhesa®... A New Hope for an Old Drug

Sara Sacco, M.D., is a neurologist at the Carolinas Headache Clinic in Charlotte, North Carolina, and the lead author of the prediction of response analysis abstract presented at the American Headache Society (AHS) Annual Scientific Meeting. Impel Pharmaceuticals showed information about Trudhesa® (dihydroergotamine mesylate [DHE]) nasal spray (0.75 mg per spray). They looked at how well they could predict how patients would respond to their migraine medicine, how patients used Trudhesa®, and its benefits over an extended period in a 52-week open trial.

The Importance of Education and Asking Questions

I had the opportunity to talk with Dr. Sacco about migraine disease, brain health, patient education, and the use of DHE in the acute treatment of migraine. I am excited to share our robust conversation with you. One thing Dr. Sacco and I have in common is a passion for educating patients about migraine. For Dr. Sacco, part of her philosophy is educating her patients on what treatments are available and how they can manage their disease. "I can't do it. You're the one suffering. But I can offer you tools and teach you how they can work."

I want to ensure that people know they are in charge of their healthcare journey. Their relationship with their healthcare provider should be a partnership, not a dictatorship. They control what they want in their bodies and what they want to explore. And they wield considerable power in this regard. It took me a long time to get to that place. Once I realized I had a say in the process, it was essential to making sure others knew they did and that it was okay to ask questions.

Dr. Sacco agrees with the importance of asking questions during appointments but also understands that sometimes patients may be afraid to ask if they feel that what they have to say is unimportant. But she encourages everyone to find somebody who is going to connect with them, who's going to listen to them, and who's going to help them find the right things to help manage their headaches.

What is Migraine?

I'm always wanting to try to reach people who may not know that their symptoms could be migraine and aren't as literate as someone like myself who is well-informed about my disease. When I talk about migraine, its symptoms, and comorbid conditions, I do it in a way so that people who haven't considered it before will think about talking to their doctor about it. 

Migraine affects more than 10% of the global population and is the second leading cause of years lived with disability worldwide. These numbers are not unknown to those who treat migraine patients, do clinical research, or are actively involved in patient advocacy. However, so many people simply do not understand what migraine is. I asked Dr. Sacco how she would explain migraine to someone who may be just starting on their migraine journey or have a family history of severe headaches and exhibit the same symptoms.

Her first-time patients say, 'Well, I have sinus headaches.' But the bottom line is migraine, and specific criteria are used to make that diagnosis. The International Headache Society indicates the following criteria: moderate to severe headache that inhibits or prohibits activities, one-sided throbbing made worse with minimal exertion, light and noise, and vomiting, which Dr. Sacco believes is the most common. She emphasizes the importance of asking them these questions. 

Dr. Sacco wants everyone to consider this because, even if a patient describes their pain as a very tight band, which people automatically attribute to a tension headache, they must lie in a dark, quiet room. We know that that's migraines, and she wants them to understand. So, the patients must understand the diagnosis criteria used because then they'll understand migraines are a spectrum and all these headaches are part of migraine.

Dr. Sacco's patients need to understand that it's not just a headache but a whole brain problem. And it doesn't just start with the headache. All this other stuff goes on before you even get the headache. And that can be just as disabling. She describes having patients who don't even get the headache pain. Still, they get all these other disabilities like confusion, anxiety, fatigue, and nausea and can't function. And that's part of the migraine too. So it's important to know that migraine is a whole-brain problem. It's a brain that is too excitable; it's too sensitive. And because of all of that, it can cause a lot of issues.

I am so glad that Dr. Sacco touched on all of those because not everybody thinks about the cognitive symptoms associated with migraine. Much of the focus is on the diagnostic criteria. However, the other symptoms she described can affect your ability to function. And that's the most significant part we need to talk about more. Instead, there is this intense focus on what's in the International Classification of Headache Disorders. I like to make people aware of those other symptoms that are just as disabling, which you might experience more than anything else on some days, and I also understand that that is part of migraine.

Migraine Stigma vs. Disability

One of the most significant conversations I am involved in is the misconception about migraine disease. Despite its level of disability, migraine stigma is still prevalent among the general population, and I wanted to explore why this gap exists. Sacco understands that it's a brain thing. There isn't a blood test or EKG that shows you have a migraine, and you can't visibly see it like you would a broken arm. You can look at some people's faces and see they've got a migraine and can't function or exhibit confusion. Most people need to understand that cognitive dysfunction.

Because we don't have blood tests, EKG, or an EEG that says, "see this as a real disease," people become very skeptical about it. For example, Dr. Sacco had a pediatric patient whose teacher didn't believe she had migraines. Her teacher never let her go whenever she needed to go to the nurse. One day the patient threw up on her desk. Now, if she raises her hand, she is allowed to see the nurse. It's almost like you have to do something theatrical to prove that you've got this disability and are suffering. 

Another thing Sacco notes are patients who push through the pain and disability with the belief that they can get through it or that it is just a headache, and that's not true. She notices her patients don't always understand how bad this is, and I completely empathized with that because I've inflicted this internal gaslighting on myself for decades. I learned to deal with it early, and I found myself pushing through my pain to show up and try to be the person I thought I needed to be for everybody else. I recognize that now as gaslighting myself. It is a behavior that I am actively trying to unlearn.

DHE… What is it, and is it an option for me?

DHE, or dihydroergotamine, has been a part of my toolkit for many years. It's not well-known enough to be considered an option. Many people I interact with have never heard of DHE, specifically, if they are chronic and other abortive or rescue options have failed. Dr. Sacco details what DHE is and how it works as an acute treatment for patients with limited pain relief.

DHE has been around since 1946, and early in Dr. Sacco's career, it was the only drug available to treat migraine. Patients dealing with an attack for several days would have to go to the hospital to receive DHE through an IV or injection. You can't take DHE by a pill because it isn't absorbed in the gut. So the only way is either by IV or injection. 

After the triptans came, when people's headaches persisted, they were brought into the hospital and given DHE to treat migraines when many other things failed. And it ended up that way because it wasn't very accessible. Notably, patients would prefer to take a pill instead of injecting themselves at home or going to an infusion center. In the late 1990s, a DHE nasal spray called Migranal came out. But the problem with the nasal spray was that it didn't get absorbed very well and didn't get into the bloodstream. A lot of it went into the stomach, and because the stomach doesn't absorb this, you didn't always get good blood levels. 

Because it only sometimes worked well, people got discouraged about using the nasal spray, which made it fall out of favor. And physicians just don't want to bring people into the hospital. So, DHE was forgotten about. Some who have always used DHE know what an excellent medicine it is. Dr. Sacco has always used it, and it has always been a viable option for her patients. But it is now being used efficiently as part of the migraine toolkit. 

What is Trudhesa®?

Dihydroergotamine is an ergot alkaloid that tightens brain blood vessels (vasoconstriction) and prevents the release of natural substances, affecting various brain receptors. We've got the new CGRP (calcitonin gene-related peptide) medications to treat and prevent migraine, but sometimes the headaches get too far gone for them to work at stopping the migraine. Since DHE is not a triptan, it does not have the side effects of sleepiness, achiness, or tightness in the chest or throat. Our current need for more convenient and non-invasive access to DHE has been the problem, and Trudhesa® provides that access which can improve clinical outcomes.

Trudhesa® is a nasal spray that can be administered at home with absorption rates similar to IV/injections thanks to the Precision Olfactory Delivery (POD®) system. Data from the STOP-31 study aims to help clinicians make better therapeutic decisions, especially for patients who do not respond to triptans or drugs that target the calcitonin gene-related peptide, or CGRP. Dr. Sacco emphasizes that DHE is a migraine treatment option that is no longer inaccessible. With Trudhesa® and its POD® delivery system, we now have a practical application of DHE. 

Is Trudhesa® Effective?

During one of the presentations given by Dr. Sacco at the American Headache Society (AHS) Annual Scientific Meeting in June, is that if you try Trudhesa® three times and it brings your headache down, the chances that Trudhesa® will for at least 75% of all your headaches is around 80% or 90%. So, if it works for you, there is a good chance it will continue working for you. 86% of people who achieved migraine freedom were still headache-free in 48 hours, and 93% were headache-free in 24 hours. So when it works, it works well and keeps the headache away. And you can trust it. Sacco says, "I think those are all critical things we need in our toolkit to treat migraines."

Side Effects

Common side effects of Trudhesa® include nasal congestion or irritation, altered sense of taste, sore throat, nausea, vomiting, dizziness, and fatigue after using Trudhesa®.

For anyone with underlying cardiovascular disease or heart disease, coronary artery disease, Prinzmetal angina (where the coronary arteries spasm), uncontrolled hypertension, or peripheral vascular disease, DHE can affect the blood vessels and cause vasoconstriction. So people that have those kinds of vasospasms should not use it. If you're allergic to ergot alkaloids and your kidneys and liver don't work well, you shouldn't use them. Using DHE with other ergot-containing drugs or within 24 hours of taking a triptan can cause excessive narrowing of blood vessels in the body.

Every patient is different, so you should talk to your doctor about what works best for you.

You can find important safety information here.

If you're unsure whether or not Trudhesa® is a good fit for you, talk to your doctor about it. Dr. Sacco says, "You don't have to spend your time in bed. Please ask questions and please see somebody for [migraine]. And know that there are other excellent options, things that have been around a long time, like Trudhesa®, that we can use to treat these headaches."

To learn more about Trudhesa®, visit www.trudhesa.com.