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 sponsor, Lilly.
Katie Golden’s doctor once told her, “I have nothing left for you to try”. That was until she was introduced to the Jefferson Headache Clinic’s ketamine infusion protocol which can be a last resort to help treat some of the most difficult chronic migraine cases. Stay tuned as Dr. Nehas and Katie explain the infusion process, efficacy, side effects, cost and more.
For more than 25 years, Lilly has been committed to helping people affected by headache, investigating more than a dozen different compounds for the treatment of migraine and cluster headache.
Molly O’Brien: Hello and welcome to Spotlight on Migraine. I’m your host, Molly O’Brien. Today we’re talking about ketamine treatment for migraine. Our guests are Dr. Stephanie Nahas — she’s a neurologist — and migraine patient and advocate Katie Golden.
Dr. Nahas, can you introduce yourself?
Dr. Stephanie Nahas: Hi, my name is Stephanie Nahas. I’m a neurologist and a headache specialist at Thomas Jefferson University in Philadelphia, Pennsylvania, where I run the headache medicine fellowship program at the Jefferson Headache Center.
Molly: So, many people might be familiar with the term ketamine or maybe some of its nicknames, but can you tell us a little bit more about the drug and how it works?
Dr. Nahas: Sure. Ketamine is an old tranquilizer. In fact, some people have said, “Ketamine? Isn’t that a horse tranquilizer?” And that’s true. In fact, it first came into clinical use in the veterinary world, mostly for large animals as a tranquilizer. But it was soon recognized to be safe in humans and became useful in anesthesia — part of the anesthesia preparation for surgery.
And an observation was made that when ketamine was used during surgery for anesthesia, there seemed to be less pain afterwards. So this led to inquiry into whether ketamine could be leveraged for pain-relieving properties separate from its anesthetic properties.
With a subanesthetic dose — a does that doesn’t knock somebody out for surgery — it puts them into a bit of a twilight state, different from an opioid, where opioids can make you not care about the pain, but it will depress your respirations. There’s a risk of lapsing into a coma. But ketamine doesn’t do that with measured doses. It makes you not care so much about the pain, and it relieves it as well.
Molly: We’re starting to see ketamine pick up, kind of gain traction used as a treatment for chronic pain and for mood disorders. Can you tell us how you treat patients using ketamine?
Dr. Nahas: We’re using it primarily for refractory migraine, but for a large number of people who have refractory migraine, they also deal with depression. And we found that for some of these patients, the ketamine may help both problems. Sometimes only one of the two problems will respond. Sometimes neither problem responds. And we’ve also seen some of our patients go in the opposite direction. When they receive ketamine, they actually become very depressed or very distressed or very anxious.
And we’re learning to identify some of the risk factors for this. One big one is preexisting post-traumatic stress disorder. So a trauma history and possible PTSD is something that we do screen for in our patients who are considering treatment with ketamine.
Molly: You talked a little bit about screening. Can you tell us who makes a good candidate for using ketamine to treat migraine?
Dr. Nahas: Well, besides screening for risk for PTSD, we’re also wanting to ensure that our patients are not at risk for other untoward effects of ketamine. We can see changes in blood pressure and heart rate, so anybody who’s got a history of arrythmia or uncontrolled hypertension, we might hesitate. Ketamine can cause liver enzyme abnormalities, so those with significant liver disease might not be a good candidate. But it actually is a pretty well-tolerated drug by most patients when used properly, with very few adverse events in our experience. And we’ve now treated hundreds of patients in the hospital with intravenous ketamine.
We do also have a few patients who only use an intranasal form. This is not as strong as the IV form, and most patients get it from a compounding pharmacy, where it’s just ketamine in an intranasal form for acute relief, not as a maintenance treatment or anything like that. Now, intranasal ketamine — or esketamine, the enantiomer of ketamine — is used in the psychiatric world. This was recently an approved product for an intranasal delivery system. That’s separate from what we do. That’s used purely in the psychiatric world and just to treat depression.
What we do is really geared towards treating the pain, and if we get some secondary positive mood benefits or other benefits, we just consider that icing on the cake.
Molly: That’s amazing. Can you tell us a little bit about numbers in terms of how effective is the drug and dosage, length of treatment? Can you talk to us about some of that?
Dr. Nahas: Sure. We have a pretty standard protocol. We start everybody off with a low rate that’s based on their weight, and we increase it very, very slowly and incrementally throughout the course of the stay, which is about five days for most patients. We have an upper limit of 1 mg per kilogram per hour, so for the average person who weighs 70 or 80 kg, 70 to 80 mg per hour is the highest dosage that they will get.
But they can’t start there because that will definitely knock them out. We need to introduce it gradually, and over time, a tolerance develops relatively quickly to this drug so that we can continue to increase the dose to get the pain relief that we need.
And what we’re looking for in our patients is that as we turn up the dose, they stay awake. They might start to develop some mild sense of inebriation. They might get what we call nystagmus in the eyes. This is one of the things that police look for on a drunk-driver test. When they have you follow the finger back and forth, they’re looking for your eyes to quiver and not go smoothly back and forth. We call that nystagmus. We’re also looking for other side effects like nausea or vomiting or out-of-body experiences or really just anything that makes the patient uncomfortable.
But there’s otherwise no exceptional monitoring required for ketamine treatment, and we’ve treated hundreds of patients now. Most of them, when they leave the hospital, their pain is better or in many cases gone completely. It doesn’t stay gone forever. A significant proportion will come back within a few weeks to a few months and tell us that their pain has remained lower.
Now, keep in mind, we’re reserving this treatment for our patients who have some of the toughest cases, where they’ve tried many, many other things, but they remain with continuous unrelenting pain and other migraine symptoms. So it’s a challenge to break through that to begin with, and to be able to completely eliminate all of those symptoms with just one five-day treatment usually isn’t achievable.
And this is the reason that some of our patients will come back repeatedly for what we might term booster treatments or interim treatments while we’re working on the other aspects of their anti-migraine plan. It’s never about just one thing, so ketamine is merely a tool that we have in our box to be able to help our patients.
Molly: I think that’s an important point that you hit on, using ketamine as a tool in that migraine toolbox, and I’m sure many migraine patients know exactly what that means.
I’d like to open this question up to the both of you. I’d like to bring in migraine patient and advocate Katie Golden, who uses ketamine as a type of treatment for migraine. I want to ask the both of you: are there any side effects or alternative effects that ketamine might have and any potential hazards using ketamine in migraine treatment?
Dr. Nahas: Well, one of the biggest hazards that we’re concerned about is liver enzyme abnormalities, so we will check that in our hospitalized patients and any of our patients who are using the nasal form for acute relief up to twice per week, just to make sure that they’re not getting into trouble.
And then untoward mood effects can occur. We’ve actually had a couple of patients become suicidal when they received ketamine in the hospital, and of course, we never give it to them again. Most patients, we do like to introduce it in the hospital setting, be it in the nasal form or the intravenous form. But I think Katie could speak to the personal experience that she’s had with the drug, and that, I think, would be more informative.
Katie Golden: Sure. So I guess just to give you an idea of what it feels like, the pain nurse who administers the ketamine and fine-tunes the doses — the very first time, she said, “I’m going to start this, and it’s going to feel like you’ve had a martini on an empty stomach.” And I was like, “Okay.” And then an hour later, she comes up to bump it up just a little more, and she’s like, “It’s gonna feel like you’ve maybe had three martinis on an empty stomach.” “Okay.” And so it’s not that bad.
As you go further and further into it, ketamine is also a dissociative. So a couple days into it, when you’re on the higher doses, if you can tolerate it, you may feel like you — the only way to put it is like floating or looking at yourself while you’re above yourself.
I definitely had to go and do this with an open mind and realize that whatever I experience is the medicine and it’s not me, and that I need to have open communications. As Dr. Nahas mentioned that some patients have become suicidal, that has not happened to me. However, usually by Day 4, I guess I’ve had so much in my system that my mood can change, and I’ve become paranoid once. I’ve — yeah –just had some crying fits out of nowhere, and I had to learn the hard way that that’s the medicine — that’s not me — and that I need to call the nurse right away, because there are meds that can help to reverse those effects, or they can turn down the amount of ketamine that you’re receiving in the IV.
So I’m not going to lie; I have seen visual hallucinations, and it’s not a pink elephant that’s flying over a rainbow or anything like that. It’s more shapes and colors, and they’re very peaceful and can be very intriguing if you just let it be. But you do have to go into it knowing that your state of mind and maybe the things that you see are going to be altered.
But definitely there’s, I guess, a signal. Put out the bat signal if something is really not feeling right or you’re like, “I don’t like this feeling at all.” There are ways for the medication to be toned down. So those are some of the experiences that I’ve had.
Molly: Yeah, and we’ll definitely dig in in a few minutes to hear a little bit more about your experience with treatment. But I want to ask — we’ll go back to you, Katie — do you use ketamine infusions along with other tools in your migraine toolbox?
Katie: Sure. I do use preventives on a daily basis, CGRP inhibitor on a monthly basis. I do use the ketamine nasal spray. Really it is just a bottle of Afrin kind of, and I will use that when my attacks are very bad. I am chronic 24/7 daily for the past nine years, so I am always at some level of head pain. But there are times when it’s up here and it won’t go away, and that’s when I reach for that.
But, I mean, I will also use other rescue meds, abortive meds, as well, and that is in conjunction with my doctor, Dr. Nahas, and us going back and forth and just trying to figure out what works best.
Molly: Great. Dr. Nahas, yeah, can you jump in on that, using the ketamine as a treatment alongside other migraine medications?
Dr. Nahas: Indeed, it is a tool in the box of our patients. And everybody’s got their own tools, their own customized toolbox, but ketamine is never the only thing that we use. Thankfully, it’s compatible with just about everything else that we utilize. There’s nothing else really quite like it that we would use commonly. We think that its activity is largely through what we call the NMDA receptor. These are specific receptors within the brain that are part of a number of different circuits and functions, including memory and mood, but also pain is where it’s really important.
And we don’t really have any other treatments that are designed for migraine that interact with this receptor. There are very few other drugs that interact with this receptor that are out on the market now. One of them is called memantine, or Namenda. It’s a drug for Alzheimer’s, and we use that as a preventive for some of our patients with migraine. It doesn’t have any of the psychoactive properties of ketamine, however, and it doesn’t seem to affect the cognition of our patients nor the effectiveness of the ketamine nasal spray when they use it. In fact, we have this notion that there might be additive effects.
Our numbers are really too small to study this scientifically, and there’s too much variability between and among our patients with respect to the other medications that they’re on. So largely, our experience is anecdotal, although we have published data on our experience, at least with respect to our hospital program.
Molly: That’s excellent information.
I want to jump back over to Katie. I’m sure a lot of people out there who don’t really know how this works but are learning are really interested to hear a little bit more about your experience and actually what it feels like during the treatment, after the treatment, and how it all works.
Katie: Sure. My introduction to ketamine — I became chronic nine years ago, and I was seeing Dr. Jess Ailani at Georgetown, who did her fellowship at Jefferson. And so after a few years of throwing the kitchen sink at me, she said, “You’ve done everything I’ve asked. I don’t have anything else at the moment that I can give you, but I want you to consider going to Jefferson.” And she explained the five-day ketamine-infusion process.
I did do a lot of research before I went to even have a consult, just to see if this was something that I was ready for. And so then I went up to Jefferson and did — they have a very, very exhaustive evaluation, and I think it’s very, very important so that they can tell which patients are really great candidates for this or not.
So while I’m in the hospital, somebody’s always with me, meaning my mom. It’s comforting, and it’s helpful because I can forget things very, very easily while I’m doing this treatment. So I need somebody to be my reminder and just also to kind of keep me grounded a little bit.
As time has gone on and I’ve had multiple treatments, I have built up a certain tolerance, and so the dosing is dependent on my weight. I’ve had blurry vision, where — some people go in thinking, “Oh, I’m going to write all my Christmas cards,” or “I’m going to do this on my computer.” That’s not going to happen, because blurry vision, double vision is very common– or it is for me — and watching TV could be hard. Stay off social media.
But over time, now I’m a vet, I feel like, and so I can now watch TV. I can now write. I do stay off social media for the most part, or if I post something, I have somebody else OK it, because people want to know what it’s like and when I’m in there, and so I try to show that. But over time, I have gotten more used to it.
And the better I feel going into the treatment, the better I’m going to feel going out. I hate the pain scale, but we’ll use it. So say my average is at a 7. That’s pretty high. And obviously the goal is to get to zero, but the reality, as Dr. Nahas mentioned, is that not everybody responds that way. And so if I can knock that 7 down to a 5, for me, that’s huge, when I go home, in my quality of life. If it goes down to a 4, that’s great. If I walk in and start treatments at a 5, and I get knocked down to a 2, that’s huge. And both have happened to me.
I’ve never walked out with no pain. As I mentioned, it’s been nine years. My expectations were set by Dr. Nahas and the team going into it, that I didn’t have this expectation that this was going to cure me, because there is no cure.
And when I get home, I will say that I am wiped out. I’m exhausted. The half-life of ketamine is very short, so within a few hours of leaving the hospital, you don’t feel any of the effects. But yeah, I’m wiped out, so it may take me a week to recover, where I’m just kind of lethargic and want to sleep a lot. And I do have the nasal spray to use when I come home.
And maybe within two weeks, sometimes probably about a month after the treatment, is when I really feel the full effects, that I really can tell a difference. It’s not immediate, but it’s like, “Oh.” I am able to do certain activities, or I find myself being more active or not taking naps in the middle of the day, that things are more on an even keel instead of the normal roller coaster of “I have no idea how today is going to go.” It may start here, or it may start here, but then throughout the day, it’ll go up here, and then . . .
So it does help me to have an even keel, and I would also say that having ketamine, when I use other abortive treatments, that it can help those to work more effectively for me.
Molly: I’d be interested in the both of you answering the question for when —
Katie: Dr. Nahas can start.
Molly: — do patients find relief? Is it immediate — and you said, Katie, it wasn’t immediate for you — and then how long that relief can last? So I think it’d be interesting to hear on that.
Dr. Nahas: Yeah, everybody responds differently to this treatment. We’ve had some patients come in, and within three days, their pain is gone, and they’re ready to go. They don’t need that whole five-day treatment. They had minimal side effects. That’s when we really feel like we hit a home run.
And those patients, when they come back to us, they may tell us that they still have headache every day or most days, but it’s no longer continuous. They get breaks. Their other acute medications work better. They’re able to dial back some of their other preventive medicines. They’re able to focus more on lifestyle modification, exercise, yoga, stuff like that.
But the other end of the spectrum is when we have patients who come in and we push it all the way. We try to push it. They just get a lot of side effects, and they get very minimal relief. But most people fall somewhere in the middle, just like with everything, where we see incremental responses over the course of the five days. And by Day 4 or Day 5, they’re usually about as good as they’re going to get. That might mean that they’re at zero.
We start dialing it back gradually, so we don’t just shut it off and let it rapidly exit the system. It does have a short half-life, so it gets out of the system pretty quickly, but we ease it down over a few hours and then send our patients home. Most of them, when they come back to see us — and that’s typically anywhere from two weeks to two months later — if they’re still doing well, they’ll tell us exactly what has changed before the hospital and after the hospital.
So when you respond, you probably have at least a 50 percent chance of maintaining that response over the course of the immediate follow-up period for weeks to months. And what we consider meaningful is going down 2 points on that dreaded 10-point scale, so going from a 7 to a 5, or a 5 to a 3. That we consider success. And these are the kinds of benchmarks that we used in the retrospective study that we published a few years ago.
Katie: So when I leave the hospital, I feel exhausted and lethargic and need maybe a week or so to recover. However, when I leave, my pain is usually knocked down by 2 to 3 points on the pain scale. If it’s more than that, that’s fantastic for me, because I am chronic, daily, 365, and 24/7.
So for me, after about a week afterwards when I’ve had this recovery period, I start to feel the effects. So I might walk out with a 4 or 5 pain level, but your body has been through a lot. So there’s other fatigue that happens, and when that starts to go away, my head pain — I walk out of the hospital maybe with a 4, and it’s pretty consistent for me about six to eight months where my average pain level is lower.
And of course, there are going to be periods of time — a week or two, or even a month — where just a conglomeration of things happen and my pain jumps up really high and stays there for a while. But my abortives work better. The nasal spray helps me to manage that as well and to kind of bring me back down.
And so I feel like ketamine is the basis for my treatment, and then I build off of that, but it has made me a lot more functional than I was a few years ago.
Molly: That’s fascinating. So, Dr. Nahas, I’d be interested to find out: what do we know about long-term effects of ketamine use for migraine?
Dr. Nahas: Well, it hasn’t been studied very rigorously or in a double-blind placebo-controlled fashion. We do have a number of patients who are using it long term, and they seem to be safe, and they seem to be responding to it. But we have to monitor for cognitive effects and liver enzyme abnormalities primarily.
Also, we have to make sure that it’s not being misused or abused. This is a club drug, after all — Special K. And it has been noted in some people who use it and abuse it recreationally that they can develop cognitive deficits that may become permanent. So that is the biggest concern — one of the biggest concerns that we have.
Molly: So, Katie, you also use the nasal spray to help with migraine. Can you tell us a little bit about the differences and your effects by using the nasal spray?
Katie: Sure. When I go home, I have a nasal spray that I can use, and I use it for when times get really bad. But I want you to understand that the nasal spray is — the effects that I’m going to feel are way different than the hospital. They’re not as intense at all. I have literally been in the middle of a speaking engagement or a round-table discussion, and I’m feeling my head pain just increase. And I take this out of my purse just nonchalantly and do just one little squirt, and it takes the edge off. I don’t feel any different. I don’t feel the dissociative effects. I am still able to speak.
Molly: And Dr. Nahas said that the spray was not — you have to get it at a compounding facility, so usually it’s not covered by insurance. Is that right?
Katie: That is right, even though I do have the Cadillac plan for insurance. I’d say in my experience, for a bottle of this size, it’s about $75 to $150, depending on where you go. And for me, this could last a month. This could last two months. It just depends on how my head’s doing. It could last three months, so.
Molly: I mean, it’s a lot, but it’s also not that bad in terms of if it lasts you that long. If it lasted two days, that’d be one thing, but if it lasts at least a month. . .
Katie: Right, right.
Molly: My only other question was what people should really look for in a provider or treatment center when using ketamine or are interested in exploring ketamine treatment for migraine.
Katie: So if you’re considering using ketamine, trying ketamine to treat your chronic migraine, Jefferson is in Philadelphia, and as far as I know, they are the only headache clinic in the US that does have this five-day protocol that has been used for many, many years. I believe that Mayo in Arizona has started doing in-patient ketamine, and so I can’t totally speak to their program, but I believe it may be a shorter amount of time.
However, there are ketamine clinics across the country. The problem is that it’s not in-patient. You may go, and you’re there for four or five hours, and then somebody has to take you home. And then you come back the next day, and you do it again, and you may do that for three to five days. But it’s not continuous. I have not tried it this way, so. I do know people with other conditions who have, and it is very helpful.
But the other problem with a ketamine clinic is that insurance — either they don’t take insurance, or your insurance company will deny it.
Molly: Katie, you talked a little bit about the cost and navigating your way through insurance. Can you share a little bit more about that, how you actually pay for this, working with insurance? And then, Dr. Nahas, maybe you have some advice for people who might be interested on how you navigate cost.
Katie: I’m just going to start like this because I’m an insurance guru now, not just because of ketamine, but for multiple reasons. Anybody who has a chronic illness is, I call, a professional patient, because you have to have these skills that other people don’t have. And sometimes they’re hard to navigate on your own.
So insurance — like I mentioned that my very first treatment, it took me a year of appeals with my insurance company to get approval. The cost for me and for the insurance plan that I have, doing a five-day ketamine in-patient infusion, it costs about $30,000. That’s obviously going to be different depending on what state you live, where you have your insurance through, what university you’re going to. So it’s going to be different for everybody.
But because of that cost, I have the Cadillac plan for my insurance, where my deductible is $1,000. And I mean, I’ll tell you: my plan, I pay $650 a month, and that’s just for me. But it’s worth it in the long run. I used to be a banker, so I’ve done the analysis on if I did a cheaper plan. But for me, knowing that I need to, for my health, go to Jefferson and do this ketamine treatment, that if I did it once or twice a year, I mean, that adds up.
I would also say that if you’re having insurance issues — whether you’re trying to get ketamine treatments at a clinic, you’re just trying to get the nasal spray, or you’re trying to see Jefferson — a resource that is really amazing is the Patient Advocate Foundation. They are at patientadvocate.org, and they are a nonprofit that they have a specific department that deals just with migraine and headache patients. It’s called Migraine Matters, and they have trained professionals to deal with those who have migraine and headache diseases and in trying to navigate. You’ll work one on one with a case worker, and so you’ll have that person throughout the entire process.
Molly: And that wraps up this episode of Spotlight on Migraine. I’d like to thank our guests Dr. Stephanie Nahas and Katie Golden. Thank you so much, both of you, for joining us.
Dr. Nahas: Thank you so much for having me.
Katie: Thanks. I really appreciate this. This was very fun, especially to do with my own provider.
Molly: And we appreciate your time. And everyone watching or listening at home, thank you so much for joining us. Until next time, I’m Molly O’Brien.
Voice-over: Thank you for tuning in to Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.
This podcast is sponsored in part by Eli Lilly and Co.
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