• 22 Dec 2020
  • 20 min
  • 22 Dec 2020
  • 20 min

Jo Cheah chats with neurologist Bronwyn Jenkins about the management of migraine – what works, what to avoid and when to refer patients. Read the full article in Australian Prescriber.


Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer-reviewed and free.

Hi, I'm Jo Cheah and this is the Australian Prescriber Podcast. Joining me is Dr Bronwyn Jenkins, who is a neurologist in Sydney. In this episode, we'll be discussing migraine management. Welcome Bronwyn, thanks for being here.

Thanks for having me.

So, could you please start by describing the defining symptoms of a migraine?

Well, I always think of migraine as more than just a headache, so it's nice if it's unilateral pulsating or throbbing and a typical moderate to severe headache, but usually you're looking for something more than just the head pain, like a sensitivity to light or noise, sometimes nausea, but they don't have to have a full hand of those things and they don't have to have those things with every headache. So you find that people with more migraines often get fewer associated features with some of the lower grade headaches, but usually if they've got some headaches that define as migraine, then you would classify them as having a migraine.

And what are some important questions for the clinician to ask when taking a history of someone with a suspected migraine? And if you'd like to add in as well, some differential diagnoses that we should be aware of as well.

Yeah, so I think the most important things, to put it in their terms, so, you know, if you say, do you have sensitivity to light? I usually say things like, would you avoid looking at bright lights, use sunglasses or avoid looking at screens, for instance. Or, do you find the TV's a bit loud and want to turn it down? So it's nice to put it into layman's terms if they're just looking at you blankly. Similarly, patients don't really understand the word nausea. So, you know, do you feel sick in the stomach is a lot more useful for a patient. But I find one of the most sensitive questions to ask, to try and figure out in those less typical migraine cases of whether it's tension type or migraine, is to ask them whether they would have a preference to rest, even if they do try and push on from their personality point of view, or whether their headache would get worse with exertion.

And I think you're right to look out for differential diagnoses. The typical age is in the young adult years, that can be earlier, it can be later, but they shouldn't be having new migraine attacks after later age, say 40 or 50 years of age. That would raise some suspicion. Usually though, if you dig, they've actually had significant headaches, like a hangover after half a glass of wine that they say, "Oh, no, that was a hangover." Whereas, of course, we know that that's not enough alcohol to cause a hangover. So I think if you dig and say, have you had any other significant headaches through life, you usually find a past history of migraine, even if there is something exacerbating in those later years.

But if you are concerned that you've got a migrainous headache, but there might be something underlying it, you'd think about inflammatory disorders like temporal arteritis in the elderly, obviously space occupying lesions that sort of our patients are often worried about, but it's not particularly helpful to know whether the headache feels like pressure or explosive as to whether or not there is something pressurised underneath it. So in those cases, which is the minority, you might want to do imaging or blood tests to double check that, you know, that there isn't anything else underneath it if it's atypical. The other nice thing is, most people with migraine will have a clear-cut family history, even if there's different severity and even if some of them have aura or don't have aura, you know, usually you can see that this fits with a picture of migraine and the recurrent headache that they've had through life, even if it has slightly changed over time.

So just on that point regarding the age of onset, is the treatment of migraines in children different to migraines in adults?

Yeah, it is quite different. We've got different medications approved. In Australia we're quite conservative, so specialists generally don't see paediatric patients unless they've got paediatric qualifications. So I don't see children, but I do know that there's a limited sort of range of treatments that we'd be more confident with because even their hepatic metabolism is not mature and other things aren't authorised, like, you know, for instance, Botox for the worst sort of cases, isn't authorised under the age of 18 because of how the trials are often done. But they present differently too, so they can be a much more non-specific headache, which looks like a tension type headache, but again, I find that the question of whether they get it with hot weather, exertion, those sorts of typical migraine triggers, is quite useful. And they get a lot more nausea or vomiting it seems, and even abdominal pain. So it's almost abdominal equivalent of migraine and some have cyclical vomiting. So it's an interesting group.

So some key words that we might associate with migraines are things like prodrome or aura and postdromal stages of a migraine. So what are these stages of a migraine?

Well, these are really significant stages and it's exciting that attention is finally being paid to them because it's much easier to measure headache days and count headache hours and headache severity. So that's what all our research focus has been on and all our treatment options are focused on. But the most debilitating features for some people living with migraine disease is the prodromal or pre monitoring phase where they are aware for hours, or even a day before the attack, that they're going to get a typical migraine. So it's the start of the migraine attack, but it doesn't respond to the headache pain treatment options. So they can already feel fatigued, alteration in how they go to the bathroom, snappish behaviour, which of course has been put down to being a trigger, which it possibly isn't, yawning. And if you show the patient that you understand there are other features that sound a little odd but are a really reliable predictor for some of the individuals, that is not all people, then they really feel that you know a lot more about migraine.

I think everyone's been aware for a lot longer about aura. So this is a clear-cut neurological event. So sometimes it only lasts for minutes. If it's polite, it'll last 20 to 30 minutes. It can last longer and it can be naughty and come in the middle of a migraine instead of before the migraine to herald the worst ones, but you really can't miss it. So the typical visual ones are zigzag lines, flashes of lights, patches of lost vision or half their vision lost or tunnel vision. And some people have quite devastating auras where they're losing the sensation or having pins and needles down the whole half of their body or worse hemiplegic down one side of the body and completely unable to drive the car or get to school pickup.

And then the final stage past the headache phase is the postdromal stage. So it's not a choice or a lazy person that's lying around feeling washed out the next day. Consistently patients describe after a full-blown migraine attack that they feel hung over or foggy in the head, unable to do their usual activities and fatigued. And so typically they're going to work, but they've got this thing of presenteeism where they're there, but they're not really there and they're not really able to do their full activities.

Yeah, interesting that you've mentioned how the migraine can impact their quality of life in their daily activities. So in more broad terms, how debilitating can a migraine be for your patients?

Migraines are really very debilitating, and they cause people to lose a lot of time from their activities and it's not just work, but it's also at home and parenting, being a partner, being a friend, being able to fulfill social commitments. Once they wake up with a migraine established, they often know to cancel everything for a few days. And I think we underestimate the debility by looking at just the headache days in our practice, but also in the research trials. Because when you add in the pre monitoring postdromal phases, you can see that it spans a lot more of their week than we recognise, unless we can treat it really effectively, that is.

Are there any risk factors that increase a person's chance of developing migraines, for example, certain comorbidities or even gender?

Yeah. So we see the graph take off in around the time of menarche for women to predominantly have migraine compared to men. And even though there can be males in the family line, it's often the women that have the worst, more difficult to treat migraines because of those additional hormonal factors. So I think of it as a polygenetic disorder in most people where you can find some family history. And then there are other factors, so obviously if there's a chaotic lifestyle with lots of triggers, you're going to have more migraines. But even if you do control all the lifestyle triggers such as sleep deprivation, alcohol, dehydration, poor diet, lack of exercise, there are some demographic type things of low socioeconomic class, obesity, that can lead to chronification, so an increased number of migraine attacks over time.

So we generally advise a healthy lifestyle to try and keep the frequency down, but in our practice, I think we're seeing the people that have tried all of those things or have tried and failed, and are still having too many migraines to function.

So let's imagine we're in a community pharmacy now or a GP practice, and could you go through some over-the-counter treatments that you could recommend for migraines in primary practice?

Yeah. I mean, it's a lot less fun in the over-the-counter now that they've put codeine behind the counter and on the scripts, and that's entirely appropriate because we were underestimating how physiologically addicted some people were and how those up-regulated receptors were probably driving their migraine frequency. So that's a good thing of the past, but over-the-counter, I think if you're using something like a nonsteroidal anti-inflammatory, aspirin's better at getting over the blood–brain barrier than ibuprofen. And a high dose of 900 mg or 1000 mg of aspirin is better than the usual 600 mg. Paracetamol is often not effective enough for adults, it's usually effective for kids for some unknown reason. And so we often combine that with metoclopramide to ensure adequate absorption and more effectiveness. So they're the main over-the-counter things, which is great because I think we were seeing people that are harming themselves more than helping themselves with the codeine medications in the past years.

Yeah, and good point that you made about the codeine, because I've mentioned, you know, reading through your article, that opioids aren't a choice of therapy in migraines, would that be correct?

Yeah. I mean, I think if someone's been on a heavy dose, obviously you can't stop it cold turkey, but they should have one person prescribing it and gradually trying to decrease it over time in an ideal world, unless they've got another pain syndrome that they have to have it for. And I think that we've seen that it's less effective in trials. So the classic trial showed that morphine in the emergency setting was less effective than Stemetil, which is not very effective in its own right. So we're not doing them favours to just help them go to sleep and go to bed with a narcotic analgesic. So we avoid codeine now. But I think there are some patients who, for their very worst menstrually related migraine once every three months, they might need some codeine on occasion. So the rule is to be compassionate and kind and reasonable, but if they're having it more often, then you need to have the discussion with them about limiting their use and they should certainly be trying other treatments if they've got better options available.

And you also briefly mentioned there, the use of combination product between paracetamol and metoclopramide, or even prochlorperazine or Stemetil just then. So what are some options that we can use for managing nausea and how does nausea impair the absorption of other medications?

Yes, I think patients often wait until they're vomiting to take something for nausea and by which stage, you know, there's such pooling of gastric acid that it's a done deal and the headache's established. And I should have said earlier that the secret, if I had to tell people one thing instead of 20 when I'm talking about their acute management of migraine, it would be to take whatever is their most effective treatment early. So I think if they take it in the first hour or two, they've got the chance of aborting or completely stopping that attack. Whereas if they see how it goes and wait until it's the worst ever headache, there's two things. One is that it may be an unmanageable headache by that stage and they'll still end up getting sicker and sicker because nothing will stop it.

But the second is that they'll usually end up having a one to three day migraine, typical of the natural history of migraine because they took their things too late to stop it earlier. With the anti-nausea treatments I usually use metoclopramide or Motiliam, which is domperidone, for that sort of motility effect, probably more than I use Stemitol. Although if someone prefers Stemitol, I'd certainly use it. And then I usually also, to throw up the back of the cupboard, give them a script for ondansetron wafers, just in case they do get to that vomiting stage. Because I think it's best to give them treatment options that they can manage their migraine at home instead of ending up dehydrated in an emergency department.

When should patients be referred to their GP for a script or furthermore to a neurologist for the management of their migraines?

So I think if they're coming in all the time for frequent painkillers to the pharmacy, it's really appropriate to tell them there's other more effective treatments that might mean that they need to take less stuff. The alarming thing is when I see someone who's taking six ibuprofen at once because it's not effective enough, and that's a disaster because they'll get renal failure, right? So I think if you're alarmed about the amount of medications they keep coming in to get at the pharmacy, you make a helpful suggestion to see their GP. And I think most GPs with the resources out there, are very confident with starting better acute treatments like triptans and preventive medications if they've got too many headaches. But if they're more complicated, they're not responding, they're still having difficult to treat headaches, then hopefully a neurologist or headache specialist can be helpful and going to sort of second-line treatments.

And starting with triptans, could you go through the medications that you may prescribe for the treatment of migraines and what are their main contraindications and side effects that we should monitor for?

Yeah, so the triptans, there's a class of five of them in Australia and they all vary slightly in the part of the receptor they target, but also in the duration and the potency and therefore the side effect profile. So in the article, there's a nice little table about the differences between them. So sumatriptan is the cheapest, easiest. We've had it for about 30 years. That's great, but if they need something longer acting, then they might try MAXALT Wafer, nice little wafer that dissolves on the tongue. But if that's not quite effective enough or they don't like the taste, then Relpax can be more effective or Zomig. But then if they need a slower onset, because they're getting side effects, then Naramig is the slowest in onset. But because of that, it's better tolerated for some people, although you don't want to miss that early window.

So there's differences in each one, so there's actually a guideline to tell people to try each one about three times until they find one that works most of the time. So if you wake up with your worst ever migraine in the middle of the night, it's likely that nothing's going to help it. But if it works two out of three times then that's considered to be effective.

So with the triptans, we wouldn't give it to someone with coronary artery disease, heart attack. I even get a little bit twitchy if they're a young person with a recent, you know, dissection of their vertebral artery or something like that. But usually it's ischaemic heart disease group that we'd avoid because there is that vascular reactivity of these.

Separate to that group, a lot of people describe a funny feeling of the triptan coming over them like muscle spasm and tightness. So they can get a tight jaw, they can even get neck tightness, which is a little bit disturbing. Most people don't get sedated with them. The whole point of triptans is so that people can get more efficiently and effectively back to their work quicker. So most people can function completely normally once they've had them rather than ending up resting in bed.

So we're at the point where patients have tried all of these things and they're still getting headaches. So can we talk about prophylactic treatments for migraines and what sort of criteria patients need to fulfill in order to be eligible for prophylactic treatment?

Yeah, so I think that we under use these worldwide, but also in Australia and this is the boring stuff that works slowly, but overall helps decrease the frequency and severity of migraines. And that's a lot more robust than the short-acting things that might not be safe in increased usage. So it's mainly for people who have more than four significant migraines a month. And so it's all in the reading of what significant means. So if they're difficult to treat, if they get to a severe stage, if they're ending up in emergency, if it's threatening their employment, then you know, these are the patients where you might think with a relatively low frequency to start up, is certainly once they're heading up to higher frequency migraine, which is anything more than nine days a month, they've got too many headaches to treat it effectively with acute painkillers. And those patients should ideally be on a preventive as long as it's well tolerated to decrease the number and severity of the attacks and make them easier to treat with their acute treatment.

And what are some of the preventative treatments? I know in the article you've described them as being off label to their registered indications. So could you talk a little bit about that as well?

Yeah, so migraines had a history of borrowing things. So we've borrowed our preventives by noticing they help from different classes. So first-line oral preventives come from antihypertensive, antidepressant, antiepileptic groups. And the weird thing to me is if you use any angiotensin II receptor blocker, for instance, it won't help migraine. But if you use candesartan, which has been proven to be effective in migraine, it will help. So propranolol, candesartan, verapamil, sodium valproate, which is the Epilim, probably some of the more evidence-based migraine preventives. And then there's some that have less evidence from less trials done and variable results in the trials.

So we've got quite a wide range and unfortunately, or fortunately, we try and choose the first treatments or the second treatment that we try, based on what is least likely to cause side effects or most likely to help with other comorbidities. So if they've got high blood pressure, great, use an antihypertensive. But if they've got low blood pressure, you're not going to get very far and you're probably not going to get to a therapeutic dose. So in someone who's got low blood pressure, you’d think about the other classes. So if they're not sleeping, you'd use something sedative at night, kill two birds with one stone, because sleep deprivation is a terrible trigger for migraine.

If they're overweight, you might use something that decreases their appetite like topiramate, as long as the other side effects were okay and compatible. So you certainly wouldn't use something that massively stimulated the appetite like pizotifen or Sandomigran. So it's not a great way to choose your medications based on what's the side effect profile. And I often find myself asking the patient out of these two options, which sounds least horrible, as far as knowing what thing they might be happy to take. Because there's a very low compliance rate with taking these medications when they have to take every day, even the days they don't have migraine, particularly if they have to take it two times a day. So we have to really engage them with making the choice in an informed way so that they're happy with that choice, and they're happy to look out for the side effects and let you know if they're not tolerating it well.

That was great, and I would recommend that the listeners look at the article because you've clearly and thoroughly listed all of those first-line treatments for prophylaxis, including the doses, timing and the timing to assess efficacy. So in your article, you've talked about a novel monoclonal antibody that is targeting the CGRP peptide. Can you talk about that medication and how you anticipate any further treatment developments in that sort of area of migraine treatment?

Yeah, so we've got three approved through TGA, but not on PBS listing. The monoclonal antibody therapies are useful for the patients who failed more than three preventives and have either disabling or high-frequency or chronic migraine. And if they do get PBS listed, they'll probably be for the chronic migraine group first, but there's a whole lot of organisation to get them on the PBS potentially. They've been absolutely life-changing for some of my patients that previously didn't respond to all the other oral preventives, even in combinations of two or three at a time and Botox and greater occipital nerve blocks and you name it, they tried it. So they're really a better tolerated class of medication for most patients. They can cause constipation, there can be some redness at the side of injection because it's a monthly injection that they have to give themselves. It's potentially a better compliance with these medications if they only have to take it once a month, instead of twice a day.

In the trials, about 50% were 50% better from their migraine days. And I think in my real world experience, there are super responders and there are those that are really much better than that and much better than I've ever seen them in the last 20 years despite trying everything. But again, because of the vascular issues, I wouldn't use them in ischaemic heart disease. So pretty much if you'd exclude someone using a triptan, I'd exclude them using CGRP monoclonal antibody until we know more about that area. And like most things, I wouldn't use it in pregnancy because people actively pump antibodies across to the unborn fetus and we don't know the effect of that. But otherwise, there's not too many restrictions and it's just a matter of getting them to be an accessible treatment.

Down the track in the future, there'll be oral CGRP antagonists, so little pills that they take every day. These were developed as an acute treatment, but have been discovered to be safe and useful in prevention. The trials are still ongoing for some of those.

I guess, to wrap things up, what are some non-pharmacological strategies that can help prevent or manage migraines?

Yeah, so I think you've got to treat the person as a whole person and everything in the head and neck feeds into the same single pain centre of the trigeminal cervical nucleus. So if they've got terrible sinusitis, forget about just giving them symptomatic migraine treatment, or if they've got terrible contemporary mandibular joint dysfunction or a terrible neck. So physiotherapy and those sorts of treatments are useful. Acupuncture has been established for a long time. It's possibly the poor cousin of Botox for some patients in effectiveness, but it's useful to trial particularly in states like pregnancy or if it's preferable to medications, if they're having troubles tolerating them. And there's a couple of little devices. So there's the Cefaly, which is a little TENS machine that they put between their eyebrows. And 30% of people don't tolerate it particularly well, but those that do tolerate it, do find it helpful some of the time. And it's got acute and preventive settings.

Thank you so much, Bronwyn. It's been great having you on the podcast. That's all the time we have for today's episode.

Thanks so much for having me.

Bronwyn's full article is available at nps.org.au/australian-prescriber. The views of the host and the guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise.

I'm Jo Cheah, thanks again for listening to the Australian Prescriber Podcast.