S6:Ep6 – What to Know About The Migraine Prodrome


Molly O’Brien: Welcome to Spotlight on Migraine hosted by the Association of Migraine Disorders. Did you know yawning, food cravings, and mood changes could be signs that you are in the first phase of a migraine attack, the prodrome? In this episode, Dr. Anna Pace discusses what happens in our brains during the prodrome and symptoms that can occur. She also talks about food cravings during the prodrome and their relationship to migraine-trigger foods. Hello, and welcome to Spotlight on Migraine. I’m your host, Molly O’Brien. Today we’re taking a deep dive into the first phase of a migraine attack, the migraine prodrome.

To help us get a better understanding of the migraine prodrome is our guest, Dr. Anna Pace. Dr. Pace is Assistant Professor of Neurology at the Icahn School of Medicine at Mount Sinai in the Division of Headache Medicine. She serves as the Director of Headache Medicine Fellowship and is the director of the Transgender Headache Medicine Program at Mount Sinai, where she provides comprehensive headache medicine care to the LGBTQIA2S+ community. She also aims to improve provider knowledge of the unique needs of this patient population. Dr. Pace, thank you so much for joining us today.

Anna Pace, MD: Thank you so much for having me. I’m really excited to talk about this topic. It’s so interesting to me, so I’m looking forward to our conversation.

O’Brien: I am too. It’s fascinating. And hopefully, our viewers and listeners will get so much out of it. So, before we talk about the migraine prodrome, can you briefly remind us about the stages of a migraine attack, to help us set the stage?

Pace: Yeah, so I think one of the interesting things about the stages of migraine is that for most people, they think it’s just a headache. But for people who do experience migraine, there’s a lot of other symptoms that come with it. Some people can have something called a prodrome, which we’ll talk about in a minute, that can be anywhere be from hours to days before the actual head pain. And there are lots of vague symptoms that come with that. Then for some people, they may experience aura, which are kind of more concrete neurologic symptoms that we’ll talk about in a little bit as well. Then the headache comes, which can be anywhere from 4 hours to 72 hours. And then afterwards, the last stage is what a lot of my patients call the migraine hangover or the postdrome. And that’s kind of characterized by more lingering type of symptoms, fatigue, difficulty concentrating, and those kinds of things. So there are multiple stages of a migraine.

O’Brien: Learning about migraine is fascinating. And the more we know, the better prepared we can be. So let’s dive into the migraine prodrome. It’s also called the premonitory phase and sometimes called the pre-headache phase. So if you’ve heard those things out there that your doctor is talking about, it’s all kind of encompassing. So, Dr. Pace, what is the migraine prodrome?

Pace: It’s basically the first phase of a migraine attack. And I think for a lot of patients, it often comes, and people don’t realize that’s what’s going on. It usually is suggesting that there’s some activation going on in the brain that the migraine has already actually started. And not everyone has prodromal symptoms, but some people do. The difficulty about the prodrome is that the symptoms are really vague. So for some people, it’s fatigue, their neck might feel kind of stiff, they might have some irritability, or they’re yawning. Those are just some examples. And that, you know, is kind of the beginning of the actual migraine process, and it can be anywhere from hours to up to 48 hours, typically, before a headache. So, sometimes it’s so separate from the headache pain part that people don’t realize it’s actually happening. And then once they get the headache, they go back and say, oh, actually, yeah, that makes sense. Something was coming. Something was brewing.

O’Brien: It’s almost like an aha moment. You’re like, oh, now I realize I was real grumpy yesterday, or whatever it is. So it’s fitting those pieces together. You touched on just a few symptoms that people might experience…they might not…during a migraine prodrome, but can you talk about a couple other symptoms that people might not be aware of that it’s the signal of migraine attack is starting.

Pace: There are many of them. I would say probably the more common ones are fatigue, the neck pain or stiffness, and mood changes. So some people may be the more common kind of mood changes, irritability or grumpiness, as you said, and oftentimes their partners or family members will say, you know, you were really grumpy or cranky. Some people also experience euphoria, where they actually have this like really happy kind of feeling, and they don’t know why. Excessive urination.

So having to urinate really frequently before is another one I hear commonly, and most people don’t put the two and two together because it doesn’t…I guess when you think about it, it doesn’t really make a whole lot of sense of why that’s happening. Some people experience nausea. They maybe already have some difficulty concentrating or feel kind of like hazy or foggy. Those are kind of the words that typically patients will describe to me. Difficulty sleeping. They may have some food cravings, hopefully we’ll get into because that’s really interesting to me. Yawning, which is another big one. And some people get dizziness.

So there are a really large range of symptoms. And I think what’s interesting, too, is many patients don’t have the same ones each time. Some people do. They’ll say, oh, you know, I have this mood change, and then I’m going to get a headache afterwards. Some people will have symptoms that change with each attack. And most patients will actually have up to about three prodromal symptoms, according to some studies about this, which is interesting. And some papers are actually saying that about three-quarters of people actually experience prodrome. And some papers are even saying 90% of people actually have this. Most of the time, I think it’s difficult to figure that out because people don’t realize the symptoms are actually related to migraine.

O’Brien: We talked about some of these really interesting symptoms that some people might experience. And you mentioned frequent urination. So some of these symptoms could be a little bit surprising. Do we know why we experienced some of these interesting symptoms like yawning, like mood changes? Do we know why?

Pace: Yes and no. I would say it is to someone who has migraine to try to connect why they would have frequent urination and yawning with migraine is really hard. When we think about what’s actually going on in the brain during a migraine attack, what some studies have shown is that there are certain parts of the brain that are activated during the prodrome that are responsible for these symptoms. So the hypothalamus, which is kind of this big control area of the brain that’s involved in a lot of other functions like your sleep-wake cycle, lots of hormone production and regulation, typically are activated very early on in a migraine prodrome or in migraine phase. And when the hypothalamus is activated, that one in particular tends to cause a lot of these symptoms that feel a little odd, like the yawning, the frequent urination.

Some people will have more like nausea, or their sleep may be disrupted before their headaches, or their cravings or food changes, they may be really thirsty. There are a number of other areas of the brain that are activated during the prodrome that we think relate to some of these other symptoms, like the insular cortex, the limbic system, which tends to control the mood kind of aspect of this. So, kind of the way I describe it to patients is like depending upon which part of the brain is active at that time, you may have these symptoms that reflect that. But the hypothalamus seems to be the big key player in a lot of the prodromal symptoms.

O’Brien: Oh, that’s fascinating. So that can really impact all different areas of our body because of what’s actually happening in our brain and our nervous system. So interesting. Let’s talk a little bit more about the prodrome. You said some studies show that up to 90%, possibly, of people living with migraine have prodrome symptoms, but not everybody does. Can you talk to us about how long does this prodrome last?

Pace: It’s really hard. For some people, it can be a couple of hours before, some people may say the day before or two days before. So when you’re trying to study the prodrome, and patients are saying they have symptoms two days before, sometimes it’s really hard to make that connection where, say, on a Monday, they’re really tired and maybe a little bit irritable, but hey, it’s Monday, there could be lots of other reasons why you feel that way. And then two days later, the actual migraine pain happens. Maybe you have an aura or something like that.

With that kind of space in between, it’s hard to connect them and say, oh, actually, maybe this was starting two days ago. And I think that’s particularly difficult for some of these vaguer symptoms where maybe you have difficulty concentrating. The fatigue I think especially is hard to tie in together because a lot of people are tired and Mondays. But it can really be very variable. I would say for the most part studies are suggesting that the average time is like six to nine hours before the migraine attack, but as I mentioned, I’ll have patients tell me the day before they’ll feel something and then they’ll wake up with the actual migraine pain.

O’Brien: Can the prodrome symptoms last?

Pace: So, I want to say yes and primarily because patients tell me this. So I go by kind of like real-world data and patients will tell me like, hey, I ate chocolate and my pain started, but I still really wanted chocolate like two hours later. The way I think about this is maybe not necessarily describing it as prodromal symptoms, but now the symptoms are part of the actual migraine like head pain. And primarily because whatever is activating the hypothalamus or other areas of the brain is still activated and continuing. So, right, so because all this activation is spreading, it’s still lingering, I guess, so to speak.

And especially for people whose prodromal symptoms are things like nausea, the difficulty concentrating, the sensitivity to light and sound, we know those as classic migraine symptoms as well. So I think it’s probably more semantics, but I would say yes, I do think that a lot of these can linger through. And when you look at some of the diagrams of the stages of migraine, a lot of them overlap. And so some people may get an aura and also still have prodromal symptoms, or the head pain will start as like the curve of the prodrome is kind of going down but not totally gone. So I do think, very individualized, of course, but I do think a lot of these symptoms do linger and can.

Patients don’t really follow the textbook in the ways like we like to try to categorize things as like this is this. And then right after this happens, then this happens. But real life is not like that. So there’s just…it’s messy. There’s lots of overlap, and a lot of these symptoms in the prodrome also can linger through the head-ache part, and then also linger into the postdrome, like especially the fatigue and difficulty concentrating. So I think it’s just very individual, and each attack is different, too. So even in the same person, they may have symptoms that linger, and other days, maybe it’s a very discrete, two hours of fatigue, and then all of a sudden they’re okay, and then two hours later they have a headache. So I think just thinking about it as a spectrum I think is really helpful. And it really, again, depends on which part of the brain is activated and for how long that’s happening.

O’Brien: If we recognize these prodrome symptoms, are there things that we can do to kind of prepare ourselves, prepare our body for the migraine attack that’s in pursuit?

Pace: Yeah. So, a lot of patients have found that doing things like dimming the lights, laying down, resting, drinking a lot of water is a really common thing that patients tell me like, oh, I chug a lot of water in hopes that maybe it’ll stave it off. I think, really, the idea when you’re having prodromal symptoms is like what can you do to try to see if you can prevent the actual head pain and the rest of the attack from happening. And so really, again, that’s kind of individual to the person. If they know that it’s a time where they’re looking at screens, they might take a break from screens.

If they haven’t eaten that day, or not a whole lot, maybe that would be a time to kind of snack and have some water and rest or kind of dim the lights a little bit. But there has been some data, especially recently, that’s suggesting that there are certain actual medications or treatments that we can do during the prodrome that would help prevent the head-pain part or a part and so on the rest of the phases of the migraine from actually happening. But in the past, what patients would typically do is lay down in the dark, drink water, and hope that it doesn’t happen.

O’Brien: Cross your fingers. And that’s interesting too because we have seen a little bit more news coming out about taking certain treatments earlier. So what do we know about using some type of treatment during that prodrome? Can it be beneficial? And can certain treatments work better the earlier that they are taken?

Pace: Yeah. So this has really been kind of an up-and-coming area of research primarily because what we know in headache is that the earlier you treat, the better. A lot of the acute therapies that we use, we always tell patients take it at the onset of head pain. But for patients who have the prodromal symptoms or aura also, taking it even earlier than the pain seems to be even more beneficial, right? Because essentially what we’re trying to do is prevent this wave of activation that’s going on in the brain. So it’s kind of like trying to prevent a wildfire. Throwing a big bucket of water on a smaller fire will be more effective than if the whole forest is inflamed. So this area of research even started as early back as in the 80s. So there was a study, in 1984, looking at domperidone early on in prodromal symptoms and how that may prevent migraine. Obviously, we don’t use domperidone regularly anymore for migraine, but that kind of set the stage for maybe we should think about using acute therapies earlier than when the head pain actually starts.

So there was one study, in 2012, looking at frovatriptan, which is a common triptan acute therapy, and another, in 2020, looking at naratriptan, specifically, and taking it earlier on during the prodromal symptoms seemed to help prevent the actual head pain from happening or for some patients reduce the intensity of the pain. And then recently, ubrogepant, which is one of the newer acute therapies in the gepant class, has really great data for preventing head pain, for people who are taking it during the prodrome. So there are a lot of different studies now looking at how can we best utilize our acute therapies earlier on for people who have very regular prodromal symptoms or who can recognize it early on.

I think the nice thing about ubrogepant that it offers compared to the triptans is we’re always worried about how frequently people are using the acute therapies. So for the triptans especially, I think it’s hard to counsel someone to say, hey, if you’re tired, or you feel a little moody, maybe try to take the triptan early. A) because you take it too frequently, could that be potentially more likely to lead you to an overexposure headache, which is hard to treat, and also are you using up all of your medication when you may need it more for the pain aspect? Ubrelvy doesn’t really have that.

So I find more in my practice I really push patients to take the ubrogepant earlier. And if people are thinking, if I feel headachy, like something’s coming, I don’t have the head pain, like take it earlier on, and people do find it actually works better and really well at preventing the head-pain part. So it’s really nice to have an acute therapy that people don’t have to kind of guess, oh, should I take it, or should I not take it, and they just kind of go for it, and it works well to prevent the rest of that attack from happening. It’s huge. For a lot of patients, it’s huge.

O’Brien: I’m so glad that you mentioned the triptans because that was kind of my follow-up question. It can be so dicey if you’re unsure, and you want to stop the headache from coming or whatever extreme symptoms you have, but you’re worried about running out, you’re worried about overuse. So I’m so glad you touched on that point. Dr. Pace, now that we know that the migraine prodrome can include a host of symptoms, one of them being food cravings, want to talk about that a little bit. Triggers are a huge topic. It’s a little controversial. So, when we’re in a prodrome, say, let’s crave chocolate. I crave chocolate, you’ve said you’ve craved chocolate. But some people think that chocolate is actually a trigger. So if they eat it, they always get a migraine attack. And we’re kind of learning it could be like a chicken-or-the-egg type questions. So what do we know about the relationship of food cravings and trigger foods?

Pace: So I love this question because I love sweets, and I refuse to accept that chocolate is a trigger for migraine. I just refuse to accept it. But I also have data to back that. So there is some data suggesting that there are a couple of areas of the brain, like the ventral tegmental area, the nucleus accumbens, and the amygdala, that are activated that are responsible for specific food cravings. So actually, I have some people told me that they crave like super greasy, savory foods, like a bacon, egg, and cheese. I’m from New York. But chocolate is a big one. And I think primarily related to how this activation is happening, the migraine has already started, and the craving is actually part of the process, not that it’s actually triggering a headache.

So what I always counsel patients is like, look, if you see that every time like you’re getting a migraine or you’re thinking about like other symptoms that may be present besides the craving, eat the chocolate, and then the headache actually comes, it really is much less likely that the chocolate is setting off the headache so much as you’re already in the migraine process, and the craving is part of that process. So I tell people eat your chocolate liberally, in moderation, of course. But as I mentioned, I refuse to accept that chocolate is a trigger for migraine because chocolate is so good. I don’t want to torture people and say don’t, don’t eat chocolate. I mean, there are some foods that seem to be, quote, unquote, triggers for migraine, but it’s so individualized. And honestly, with what we know about how many parts of the brain are active during the prodrome, it makes sense to me that something has already happened, and this is just part of the process and less that it’s actually causing the headache itself.

O’Brien: I’m definitely in your camp that I refuse to believe that these foods can trigger a migraine attack. They might for some but chocolate not for us. I’m in that camp. Absolutely. And it’s really interesting because some people do crave greasy foods. Some people do crave chocolate, some people crave carbs. I actually know someone who craves a lot of vegetables, which I’m like, I wish I had that one. That seems like a good one. But it’s so fascinating that because we can place a lot of guilt on ourselves for eating some of these potential trigger foods, thinking, well, I ate this or that, and then it caused migraine. So do you have any advice for patients when you’re telling them that, that maybe they feel guilty that they ate XYZ and then it caused a migraine?

Pace: Yeah, I mean, I see this a lot. And I think that’s really where a lot of the controversy is with triggers specifically, not just food cravings but other things. You know, people with migraine don’t need any more guilt or blame on themselves that they are causing their headache attacks or that they’re doing this to themselves. Like their brain is responding to whatever is going on there, and it’s not of the fault of the person at all. So I think that’s really important to make that distinction. And life is short, and people need to be able to enjoy things in moderation. And it’s possible that certain foods are absolute triggers, but that tends to be more rare. So having migraine is not your fault. And having chocolate because you want to eat chocolate is not your fault that you’re going to give yourself a migraine. There’s a good chance that the migraine had already started, and the chocolate is part of that.

So a lot of what I think we, as headache specialists, try to do is take that blame off of the patient and say, a lot of what’s happening in your body, you’re responding to what’s going on in your brain. It’s not that you are giving yourself a headache because who wouldn’t want to do that to themselves anyway? But I do think that is, I think, the big controversial aspect of triggers is how it can be misconstrued as you are doing this to yourself because you didn’t have enough water, and you ate your carbs in the morning, when maybe you should have something more healthy, something like that.

O’Brien: I love the way that you explain that to take the blame off of patients because there is a lot of migraine guilt out there. And you mentioned too that some foods can actually be triggers for some people. So how can we tell the difference between an actual migraine-trigger food and then the food cravings that occurred during the migraine prodrome, or is it just too murky water?

Pace: That is a hard question. I wish I knew like a good answer for that. I’d say it really is lucky. So there are some foods that have been notoriously cited as triggers, like aged cheese, certain alcohols, like wine can cause headache, like dense meats. Those are kind of big ones. But again, some people can eat those without a problem. I would say keeping a diary and seeing how consistent the headaches are in relation to the food that is being ingested. If it’s pretty clear, and there’s nothing else going on, then it’s probably more a trigger and less of a food craving. But it’s really hard to tell. And then you kind of have to just have a conversation with the patient, and say, hey, you really love this food.

It gives you joy. If it so happens that it’s part of the prodrome, okay, we know if you’re craving this, maybe we can do something else to try to mitigate whatever could potentially come afterwards. And same if it’s a trigger. If you really enjoy eating certain aged cheeses, as long as it’s in moderation, and we have an idea of good tools that we can give you if you do get an attack, then let’s go ahead and do that if you’re going to eat that particular food. I think there are lots of ways to kind of work around it if it’s a really important part of a person’s diet or culture or day-to-day routine.

O’Brien: Absolutely. That’s such a beautiful way to put it. Being able to get to know yourself and your body a little bit better so you can understand migraine, and then work with your healthcare professional to figure out the best way to create a plan and go about living so that we can all enjoy life a little bit.

Pace: Exactly. I mean, the whole point of our job is to get people to go back to work and live their lives and not have to worry about migraine. And we do the best we can, but sometimes it’s a matter of discussing like what’s important to you, what are your goals, and how can we help you continue to do the things that you want to do?

O’Brien: Absolutely. Well, we’re winding down on time. So thank you so much for joining us, Dr. Pace. It’s been such a pleasure to chat with you today. Thanks, again, for all of your insight, and I think we need t-shirts that say Team Chocolate.

Pace: 100% agree. And thank you so much for having me. It was really great to speak with you.

O’Brien: Thanks so much for being a guest here on Spotlight on Migraine, Dr. Anna Pace. We appreciate your time and all of your insight. And for those of you watching and listening, thanks so much for joining us. I’m Molly O’Brien. We’ll see you next time.

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