Episode 35: What Patients Need to Know About Neuromodulation






Voice-over: Welcome to Spotlight on Migraine, hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease. This episode is brought to you in part by our generous sponsors, Amgen and Novartis.


What neuromodulation devices are available to migraine patients? Who is a candidate for this treatment? How exactly do they work? Find out as host and migraine patient Molly O’Brien interviews headache specialist Dr. Ravinder Singh.


Since 2015, Amgen and Novartis have been working together to develop pioneering therapies in Alzheimer’s disease and migraine. Together, Amgen and Novartis share in a mission to fight migraine and the stereotypes and misconceptions surrounding this debilitating disease.


Molly O’Brien: Hello, and welcome to Spotlight on Migraine. I’m your host for today, Molly O’Brien. I’d like to say hello and welcome to our guest today, Dr. Ravinder Singh. Dr. Singh joins us as a certified neurologist with a specialty of treatment on neurological diseases. So before we begin our discussion today on neuromodulation devices, I’d like to say hello, Dr. Singh.


Dr. Ravinder Singh: Well, thank you for inviting me to be on today’s show. I’m glad to be here.


Molly: So glad to have you join us today. Dr. Singh, can you tell us a little bit about your background before we jump into our discussion?


Dr. Singh: Yes, as you mentioned, I’m a board-certified neurologist, and I practice in the Los Angeles area. I am a headache specialist, but my initial training was in stroke. I trained in stroke and epilepsy, but then when I went into private practice, I was treating a lot of headache patients and so over the years. And I started my own institute called Beverly Hills Headache Institute. 


In my practice, I combine both Western and Eastern medicine to help my patients achieve better health. So it’s not just about giving them medications, but looking at all aspects of their life and sometimes even using Eastern methods such as acupuncture or yoga therapy or chiropractic treatment in my practice. So it’s truly an integrative center that I have in Beverly Hills.


Molly: That sounds pretty incredible. So anyone interested, you can look him up if you’re out on the west coast.


Dr. Singh: Thank you.


Molly:  Okay, so for today, we are going to jump into our discussion about neuromodulation and neuromodulation devices. So for those people out there who aren’t quite familiar about this topic, can you talk to us just briefly what neuromodulation is?


Dr. Singh: Well, neuromodulation is conducted with a device that uses either electrical currents or magnets to modulate or change the brain activity. Researchers found that this treatment can be effective in reducing migraine attacks as well as cluster headaches. So some of these devices can actually abort the actual attack, so they’re being used for acute treatment. And some of them are used for prevention, to prevent further attacks from happening.


So they all work differently, but the rationale is that they are modulating the activity of the trigeminal nerve pathways. As you know, the trigeminal nerve is the main nerve responsible for our headaches, and so these devices modulate the activity of this nerve.


Molly: So there are a couple current FDA-approved neuromodulation devices out there. How do those current ones help with migraine?


Dr. Singh: Well, there are actually three different devices which have been approved for migraine and/or cluster headaches, and they all work a little differently. Two of them are electrical devices. One of them is a magnetic device. So we can go through the three different devices.


The first one that came on the market is called a single-pulse transcranial magnetic stimulator. It’s a handheld device and works by generating a magnetic impulse. So you put the machine on the back of your head and neck, and the magnetic impulse — it’s just a single-pulse magnetic impulse. You push the button, and it actually modulates the nerve in the back of the head. And this was the first device that was approved for acute treatment of migraine with aura and has recently been approved for the preventive treatment of migraine. So that was the first device.


The second is the vagus nerve stimulator. Now, the vagus nerve is the major nerve of the head, and it goes to the whole body. It has been shown that usually, it works with your heart, with your lungs, and with your gut, but it has been shown to modulate brain activity. We found that out years ago when we were treating patients with epilepsy. But as we were treating patients with epilepsy with the vagal nerve stimulator, we found that some of them had improvement in their headaches. So then the company decided to make a non-invasive vagal nerve stimulator that the patients put on their neck and stimulate the vagus nerve and that somehow also modulates the brain activity. And that has been approved for patients with episodic cluster as well as the acute treatment of migraine headache.


And then there’s a third device. It’s called the transcranial supraorbital — which is in the front of the head — so it’s a supraorbital neurostimulator, and it also uses electrical impulse stimulation to stimulate the supraorbital nerves, which are part of the trigeminal nerves. And this is also shown to be helpful in reducing migraine frequency and is currently approved for both preventative and acute treatment of migraine.


Molly: That’s very interesting. Every migraine patient is different. When do you suggest patients use neuromodulation devices?


Dr. Singh: You’re right. Every patient is different, and we look at the circumstances of the patient and what other treatments have they used. So, for example, if it’s an established patient who has used many other drugs or different treatments, and if there’s a concern for medication overuse headache, for example, if they’ve been using a lot of drugs, the benefit of these devices is that they are non-invasive and they are external devices. You’re not ingesting them. And so they are easy to use, and as a result, they can be very helpful in patients in whom we don’t want a lot of medications. That’s one of the areas in which we use neuromodulation, or if the patients are not tolerant for different drugs or they are having a lot of side effects when they take medications, so we can use these devices in those instances as well. 


But we discuss them with all patients. And sometimes even if they’re new patients, they don’t want to take any medications. We can start out with these devices to see if they will be helpful and maybe add medications later on if these devices are not doing the job properly.


Molly: So who makes a good candidate to use a neuromodulation device?


Dr. Singh: Yeah, so that’s very important question. So as I mentioned, the patients who are overusing their medications — can be very helpful instead of adding another medication, and they’re not getting much benefit. So that would be one area in which we can use neuromodulation. If somebody wants to limit the amount of oral medication that they want — even though they’re not overusing them, but they just don’t like taking a lot of medications, this could be for them. Patients who have had partial response to their medications, and they want to add something, but they don’t want to add another drug — this could be used for those patients. And so those are the majority of the patients in whom we will use neuromodulation.


Now, there is another category of patients who are pregnant. Now, none of these are FDA-approved for pregnancy because whenever we are doing trials on new devices or treatments, we usually exclude the pregnant patients. But many doctors are using these because they are so safe. In pregnant patients [inaudible], we want to avoid the use of many medications. But that’s an off-label use for these devices.


Molly: Okay. That’s an interesting point you make there. I want to ask you if anyone is at risk for using these, and then we can also talk a little bit about side effects.


Dr. Singh: Right. Basically, we try not to use them on patients in whom these devices have not been studied. Now, these are electrical — at least two of the devices are electrical devices, so any patients who have any kind of electrical devices in their body such as pacemakers or a hearing aids implant or any other implanted electronic device, we don’t want to use these electronic stimulators. Patients who have carotid atherosclerosis, if they have narrowing of the arteries in their neck, because we are pushing — at least the vagal nerve stimulator, we are pushing in your neck, which is around the carotid artery, so we just don’t want to take any chances, although there hasn’t been any side effects noted.


Patients who have already had — who had their vagus nerve cut for some reason, we don’t want to use a vagal nerve stimulator. If somebody has significant high blood pressure, hypertension, or significant low blood pressure, or the heart rate is slow, which is called bradycardia — but the vagal nerve, as I mentioned earlier, it innervates the heart, the lungs, and your GI system, so it usually slows down your heart. So if you already have a condition where your heart rate is slow or blood pressure is low, you don’t want to further make it worse. So those are some of the patients in whom we would not use the vagal nerve stimulator, for example.


And again, if the patient that — we mentioned electronic devices, but if they have some sort of bone screws or any kind of other metal in their bodies, especially around their neck — if they have in the cervical spine, if they have a bone screw, which is a metal, you don’t want to be — you don’t want to have an electronic device near there as well just for safety reasons.


Those are the main patients in whom we would not want to use all these devices, but for the majority of our patients, especially the younger patients who don’t have any pacemaker or any such devices, it’s a very effective treatment.


Molly: So let’s talk about that. How effective are these devices? What do you know about their efficacy, and what’s the success rate?


Dr. Singh: Well, all of these have different success rates. Now, for the gammaCore, which is the vagal nerve stimulator, almost half of the patients had little or no migraine pain within 2 hours after first using their device. Obviously, it is not effective for everybody, but no drug or any treatment is effective in 100% of patients. But a lot of patients do experience significant effects, and the majority of the patients who achieve pain freedom at 2 hours remain pain-free for 48 hours. So if it works for you, it can work really well. It provides relief for almost 50% of attacks in any migraine patient.


The success rates for the other devices are somewhat similar, with the TMS and the supraorbital device as well.


Molly: So I read that there are some challenges for evaluating the evidence of neuromodulation. What challenges do you see facing neuromodulation devices, and how can we overcome those?


Dr. Singh: When headache specialists were designing these studies, it is kind of hard — first of all, it’s a limited number of patients in whom we can study. So in order to generalize treatments to a larger population, I think that’s obviously a limitation of a smaller study. We don’t know how effective it’s going to be in a larger group of patients.


Secondly, when we’re doing the studies, we like to do what’s called a double-blind study, which means that the patient doesn’t know what he or she is getting and even the doctor doesn’t really know which patients are getting the actual treatment versus a fake treatment. When you’re taking medications, it’s easy to double-blind because we can create the medications and sugar pills that look similar so you don’t know if you’re actually taking the medication or taking the sugar pill, which is called a placebo. 


In the trials of devices, well, how can you double-blind a person when you know you’re holding a device? So they create similar-looking devices that may not — they’re called sham devices, where you’re not getting the actual treatment. But sometimes, patients will know when they feel a little current going through versus another device that doesn’t have a current going through. So that’s a limitation of really knowing that this is really, truly a double-blind study or not. 


Now that the devices have been approved, the major challenge for patients is the cost, because these are new devices. They have been approved by the FDA, but insurances are still not covering. Or they may have started to cover, but they cost a lot, and so there’s a lot of out-of-pocket cost for the patients. 


So you kind of have to balance the benefit of these devices versus the cost, especially for our patients. And I know that the makers of these devices, they all have some sort of patients’ assistance programs. So obviously, I can’t go through all the patient assistance programs. I don’t even know all of them [laughter], but if somebody’s interested, there are ways in which the cost can be avoided or at least minimized so that you are not paying a huge out-of-pocket cost.


Molly: Yeah, so we talked a little bit about some of the challenges, and we talked about some of the success rate. But I’d like to kind of keep that conversation going, because to me, as a chronic migraine patient, this almost seems to good to be true. You’re telling me no medications, you’re telling me no needles, and you’re telling me a pretty decent success rate, comparatively. So why don’t more patients have these conversations with doctors about these devices, and why aren’t more patients choosing this?


Dr. Singh: Well, I think the main reason is that they just don’t know about and that the doctors may not be discussing them either. We’re so used to taking medications, and as patients also, there’s a certain suspicion. But as you mentioned, they’re not medications that we’re ingesting, so how are they doing their — how are they causing the effect? 


But as we discussed earlier, the studies have shown that these are effective, and the move is towards going — as little medication as possible going forward. The whole purpose is to try to stimulate the nerves which cause the pain without having a lot of side effects. So that’s where we’re going. And I think it’s a great idea for patients who are suffering from migraine — it is important that they go to their doctors and ask them about these devices and — so the doctors can find out more about them if they don’t know and prescribe these, because I think that’s the way of the future now.


Molly: Let’s talk a little bit about two things you brought up: a couple more things in the pipeline — which I’m always curious to talk about — and then continuing that conversation on cost because I think that is a big barrier in a lot of patients’ mind. One, I want to know what’s in the pipeline that you might know about that you can share with us. And then two, with more devices in the pipeline, does that open up the marketplace and then potentially bring down cost?


Dr. Singh: Right. So some of the newer devices: I mentioned that there is the vagal nerve stimulator that we put in the neck. Now there is a new device that is trying to stimulate the vagus nerve but through the ear. It’s called the auricular VNS. So that’s another device that is being studied right now. 


There’s a device which stimulates the occipital nerves. So a lot of patients with migraine headaches have pain in the back of the head, and the main nerve that is responsible for pain in the back of the head is called the occipital nerve. And so there are certain devices that are being designed to stimulate the occipital nerve without giving any injections. Now, some of the headache doctors, we actually do nerve blocks. We inject medication to block the occipital nerve, but that’s an invasive treatment. So this new treatment is looking at a transcutaneous stimulation of the occipital nerve to see if that will help with migraine patients.


The other one is called caloric vestibular stimulation, which is a device which looks like headphones, and there’s a little probe that goes into the ears, and that heats and cools the vestibular nerve. And the vestibular nerve then goes into the brain to modulate the trigeminal complex. 


There is another treatment called Nerivio Migra, which is a patch that you put on your forearm on the skin and that actually is activated by your phone. So it’s a remote device that when you have a headache, you — and so it’s for the acute treatment of headache. So patients who have these headaches frequently, they can put this device on their arm or forearm, and when the headache strikes, they just click a button on their smartphone, and it’ll activate this device to hopefully get rid of the acute pain.


Molly: That’s all very exciting, and while you’re talking about this, I just have a huge smile on my face [laughter]. I just think, what an exciting time in healthcare. So hopefully, some of those come to fruition, and hopefully, they work [laughter].


Dr. Singh: Yes, definitely. I mean, that’s the whole idea. The whole purpose of these devices is to find one that will work for you. What’s exciting for me as a headache physician is that what it does, it opens up our toolbox, our headache toolbox. Not everybody’s going to respond to all of these devices or even the medication that we have or different treatments, so it’s about finding the right treatment for the patient that is sitting in front of you.


Molly: Yes, definitely. So it must be exciting, yes, as a provider as well to be able to have different tools to be able to help you, patients, as well. All right, well, thank you so much for joining us, Dr. Ravinder Singh, for Spotlight on Migraine. I’d like to thank all of you for joining us today. I’m Molly O’Brien, and we’ll see you next time.


Dr. Singh: Thank you very much.




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