Background: Migraine Facts
Migraine is common and disabling. It is more common than diabetes, asthma and epilepsy combined and is the seventh most disabling disorder amongst all diseases. Global prevalence is 14.7% (1 in 7 people) which is around one billion people globally.
Migraine is three times as common in women (18%) as it is in men (6%). The reason women experience more migraine than men likely relates to the hormonal triggers that many women experience.
Amongst neurological diseases, migraine is the leading cause of disability. In addition to all the disabilities, there are associated financial burdens and costs that are associated with migraine. This relates to healthcare costs as well as lost productivity due to missed days of work, compromised productivity at work or underemployment due to illness.
Despite all these facts, migraine remains underdiagnosed and undertreated.
There are several potential reasons for this, perhaps the most important and pervasive is that many people still do not recognize a migraine as a real medical problem. Others may consider migraine to be a purely stress-related or a psychological issue when in fact it is known as a true neurological disorder.
We have a much better understanding about the mechanisms and pathophysiology of migraine today than we have had before. Having said that, there is no cure. However, effective treatments can significantly improve patients living with migraine. The lack of awareness of these treatments is the driving force for initiatives like Migraine & Headache Australia’s Awareness Week. This awareness campaign is an effort to increase education about migraine, not just to patients and the general public, but also to healthcare professionals ranging from medical students to advanced trainees, GPs and specialists.
Before migraine can be treated it needs to be diagnosed. The International Headache Society has a comprehensive classification system that is used to diagnose all the different types of headache disorders. Below is the criteria for Migraine Without Aura.
Migraine Without Aura Diagnostic criteria:
- At least five attacks1 fulfilling criteria B-D
- Headache attacks lasting 4-72 hrs (untreated or unsuccessfully treated)2;3
- Headache has at least two of the following four characteristics:
- unilateral location
- pulsating quality
- moderate or severe pain intensity
- aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)
- During headache at least one of the following:
- nausea and/or vomiting
- photophobia and phonophobia
- Not better accounted for by another ICHD-3 diagnosis.
By definition, in order to have a diagnosis of migraine, someone needs to have had five episodes of migraine, which lasts from four to 72 hours. Those headaches need to have two of the following four features, which are unilateral location, throbbing quality, moderate or severe intensity and worsening with movement. In addition, nausea and/or vomiting or light and sound sensitivity must be present.
About a third of people with migraine have neurological symptoms that occur before or during a migraine. These are referred to as auras and are usually visual, sensory or language related.
Visual symptoms can include flashing lights, wavy lines, or blind spots. Sensory symptoms can be numbness or tingling. Language disturbances are often an inability to articulate what is intended. They know what they want to say but just can’t seem to get the words out. These aura symptoms usually develop gradually over five minutes and typically last from five minutes up to one hour. The headache phase of the migraine will usually start either during the aura or within an hour afterwards.
The diagnostic criteria can be difficult to remember so a simpler screening tool was developed to aid in recognizing and identifying migraine. It is called ID migraine and is based on three major features of migraine which are nausea, disability, and light sensitivity.
Source: Lipton RB et al. Neurology 2003. 61:375-382
If someone answers yes to two or three of those questions above, there is a high likelihood that they have migraine.
Most people with migraine have what we call an episodic pattern, meaning that the migraine will occur relatively infrequently. For most people, that pattern stays stable or even improves over the long term.
There is a subset of people with migraine who have headaches and migraine attacks that evolve and increase over time. When they get to a point where headaches occur on 15 or more days per month, eight of which meet criteria for migraine, then we consider them to have progressed from episodic migraine into a chronic migraine pattern. Not surprisingly, chronic migraine is associated with more disability, lower quality of life, and higher levels of anxiety and depression. Chronic migraine is more difficult to treat than episodic migraine.
The best way of treating chronic migraine is to prevent it from occurring in the first place.
There are known risk factors for the chronification of migraine:
- Medication overuse
- Caffeine overuse
- Stressful life events
- Sleep disorders
- Other pain syndromes
Medication overuse is probably the most important one. Acute medications are those which are taken at the onset of a migraine attack. These may be treatments such as Panadol, Panadeine or the triptans. Medication overuse refers to using too much acute treatment. When people use these treatments more than two or three times a week, over time they can develop a more chronic pattern of headache and migraine.
Medication overuse is an important and pervasive problem in the headache population and is something that clinicians and healthcare professionals are trying to educate the public about. For more information about medication overuse, visit our dedicated article on this topic.
Many risk factors for developing chronic migraine are modifiable and can be improved or addressed to reduce the likelihood of someone developing more frequent or chronic patterns of migraine. This reduction of risk factors is part of what your clinician is doing when they are thinking about preventive strategies. It is not just treating the current state of affairs and the number of attacks that the patient is currently having. It is also trying to prevent further progression.
There are three main categories of migraine treatment:
- Lifestyle modifications
- Acute treatment
- Preventive treatment
Everyone with migraine qualifies for lifestyle modifications and acute treatments. Not everyone may qualify for a preventive medication for migraine. Preventive medication is appropriate when migraine significantly interferes with their daily routine. This may be when someone is having one or more migraine attacks per week. However for some patients, one or two migraines per month might be too many.
Preventive treatments refer to those therapies or approaches which are performed or proactively taken on a regular basis to reduce your frequency, severity and duration of headaches.
Preventive treatment may also be considered if a patient is not responsive to acute treatment, or their current treatment is associated with side effects, or if they have contraindications to the usual acute treatments.
Patient preference should also play a role in the consideration of preventive treatment. This refers to how the patient feels about their current headache pattern and whether or not they think that they would benefit from preventive treatment.
Goals of Migraine Prevention
Preventive treatments aim to reduce the frequency, severity and duration of migraine attacks.
The intention is also to reduce the disability associated with migraine. People living with migraine should be able to do the things that they want to do or need to do with as few side effects as possible.
This can sometimes be challenging to achieve. For many years, the options available did not work very well or were associated with troublesome side effects. There has been a major gap in migraine treatment for a long time.
Preventive Treatments For Migraine
There are many different types of preventive treatments available. Often medications are thought of first, particularly with the new anti-CGRP monoclonal antibodies that have become available recently.
The focus on medications can often mean that the numerous non-drug options that are available for migraine prevention are overlooked. Lifestyle modifications can be very effective and are often underestimated in the overall treatment plan that a patient may receive.
Lifestyle changes not only promote a healthy lifestyle, but they allow people to be more active participants in their migraine care. Sometimes a few very simple changes in daily routine can make a big difference in the migraine pattern.
Preventive treatments options:
- Lifestyle modifications
- Conventional migraine preventives
- Onabotulinum toxin A (Botox)
- Anti-CGRP monoclonal antibodies
- Complementary and alternative treatments
Lifestyle modifications can make a big difference in a patient’s migraine pattern. These are based on the premise that migraine patients tend to be sensitive to changes within their body and within the environment. Many patients with frequent migraine will agree that any little change from the day-to-day routine or a status quo can trigger a migraine attack. Lifestyle modifications include:
- Regular aerobic exercise
- Sleep hygiene
- Regular meals – no skipped meals
- Role of caffeine
- Dietary triggers
- Alcohol reduction
- Recognition of triggers
Many common suggestions that are recommended are intended to help people living with migraine maintain a regular routine. Regular aerobic exercise can be helpful. It is usually recommended that those with migraine undertake approximately 30 minutes of cardio exercise a few times a week.
Regular sleep also makes a big difference. Many people recognize that too little sleep or sleep deprivation can often trigger an attack.
Too much sleep can also be a trigger for some people. Sleep is a good example of how something that’s different from the normal routine, even if it’s considered positive, can actually be a migraine trigger. Many people feel that they do not get enough sleep during the week and then they want to sleep in on the weekend to catch up, only to wake up with a painful migraine.
Clinicians recommend that people try and go to bed and wake up at roughly the same time throughout the week, and all the other recommendations for sleep hygiene apply here as well. Using devices or too much screen time such as television before bedtime is discouraged. Try to maintain a regular routine so that your quality of sleep is optimized.
Hydration is a very basic recommendation that often falls by the wayside in our busy lives. Dehydration can trigger a migraine. Practical tips such as staying hydrated and keeping a bottle of water nearby can help.
Regular meals can also make a big difference, particularly for people who find that hunger is a trigger.
Food that is relatively low in carbohydrates and higher in protein is generally better because fluctuations in blood sugar can be a trigger for migraine as well. The protein portion does not need to be a big steak, it can be a handful of nuts for a snack or fish or legumes or something similar. Having some protein with each meal can help to keep your blood sugar stable and potentially avoid other attacks.
Caffeine can be tricky, especially in cities where coffee is a big part of the social culture. For most people, one coffee a day is fine, but when you find that you’re drinking more than that on a regular basis, that’s probably too much.
Caffeine can actually be associated with a rebound headache in the same way that medication overuse can. If you are drinking increasingly more caffeine, you may find that you could be having more and more attacks. A good way to tell if you’re having too much coffee or caffeine is if you have a withdrawal headache or migraine if you miss a coffee.
When consumed in smaller and less frequent amounts, caffeine can also be used as an acute treatment. Many of you may have found that a coffee or a Coke can actually help if you have a migraine and that likely relates to the effects of caffeine on blood vessels. Caffeine can also aid in the absorption of some of the migraine treatments that can be used for acute treatment.
That is an important reason to try and limit your caffeine intake. If you’re having too much of it, it can cause more migraine attacks or headaches. If you’re using it relatively infrequently you can actually use it as an acute treatment on those occasions when you have a migraine attack.
Dietary triggers can be challenging to truly uncover. Many people wonder about specific foods to avoid, or migraine diets, or things that are thought to be dietary triggers for migraine. Certainly if you followed every list out there and a strict “migraine diet,” you would not be eating much of anything because the lists are so extensive.
Generally speaking, the closer something is to its natural form the better. We are trying to avoid foods that have a lot of additives and preservatives because some of those things can trigger migraine. Alcohol is a well known trigger for migraine, as are a few other things like MSG or nitrates which are associated with cured meats or deli meats. Artificial sweeteners can also be triggers.
For the remaining items not mentioned above, there is not strong evidence to indicate that there are certain groups of foods or other foods that are convincing headache triggers. Each person may have something that seems to trigger their attacks on a regular basis, however these can vary significantly from one person to another.
It can also be challenging to assess whether or not something is really a migraine trigger because triggers are often inconsistent. Something may not always trigger an attack. The timeframe for triggering an attack can also vary. Individuals may not realise if the trigger was something that you ate an hour before or the day before.
Many of the reported triggers are not applicable to everyone. We mentioned alcohol, which does appear to be a consistent trigger for many people relating to its effect on blood vessels and sleep disruption.
Recognizing what your triggers are can be helpful to assist in managing migraines.
This is a list of conventional preventative medications.
- Blood pressure medications
- Beta-blockers – propranolol, metoprolol
- Calcium channel blockers – verapamil
- Tricyclic antidepressants – amitriptyline, nortriptyline
- SNRIs – venlafaxine, duloxetine
- Sodium valproate
Many of these treatments have been used for a long time and many of them work well for some patients. Treatments such as beta blockers, tricyclic antidepressants and some of the anti-epileptics, particularly topiramate and sodium valproate, have a good track record of effectiveness.
The challenge is that not everybody responds to them and that some of these treatments are associated with significant side effects.
Part of the reason that they do not work very well or very consistently for a lot of people with migraine is that they were not actually developed as a migraine treatment. These treatments were originally designed for other conditions or diseases like high blood pressure, seizures, or depression and were only incidentally or indirectly found to be helpful for migraine.
Botox for Migraine
Botox has received a significant amount of attention in recent years. It has been around for a while for a number of other medical conditions and cosmetic applications. It first came to the attention of neurologists and headache specialists, probably in the 80s, when a lot of women who were having cosmetic Botox found that their migraine condition had significantly improved. In Australia, Botox has commonly been used for migraine for several years with good results and received coverage on the PBS a few years ago. Usage of Botox for migraine has increased and has now become a standard of care for people with chronic migraine who have not responded to three or more traditional preventive migraine treatments.
While Botox is on the PBS for chronic migraine, there are still criteria to be fulfilled. Patients need to have tried or have contraindications to three of the standard preventives first. Medication overuse also needs to be addressed.
There is a specific protocol that is used for Botox injections. These are not the same injection locations and doses that cosmetic surgeons use for wrinkles around the face. The protocol is based on large scale international studies that have demonstrated a significant decrease in headache days in people who undergo treatment every three months. Injections are made in the forehead, temples, back of the head, neck and shoulders. The standard protocol involves 31 injections. These are generally quick injections using a small needle.
It is important to note that injections are repeated every three months for a period of time. Sometimes the injection interval may be increased out to three and a half or four months. Eventually, after successfully extending the injection interval, injections may be ceased in some patients. To continue using Botox through the PBS, patients need to experience a 50% decrease in migraine frequency compared to their baseline.
Botox is generally well tolerated. Patients often prefer Botox because it does not involve daily medications nor any of the cognitive side effects that are often associated with the other preventative treatments.
Anti-CGRP Monoclonal Antibodies
The anti-CGRP monoclonal antibodies have received attention in the past year or so since they have become available in clinical practice through various programs sponsored by drug companies. The anti-CGRPs have also caused quite a lot of excitement in the headache world because they are the first migraine-specific, disease-targeted treatments to be developed.
CGRP (calcitonin gene-related peptide) is a neuropeptide released during a migraine attack. It is thought this protein or neuropeptide plays an important role in the migraine mechanism or pathophysiology. It’s involved in the dilation of blood vessels, the inflammation in the coverings of the brain that occurs during a migraine and also the perception of pain itself.
There are three anti-CGRP antibodies that are in various stages of approval here in Australia.
- Aimovig (erenumab)
- Emgality (galcanezumab)
- Ajovy (fremanezumab)
The first is Aimovig, which is a brand name for the drug erenumab. This one is slightly different from the other two in that it is an antibody to the CGRP receptor rather than the CGRP protein itself. Aimovig became available late in 2018 through various programs sponsored by the drug manufacturer, Novartis. So far results have been positive. Many people are experiencing a significant reduction in their migraine frequency and severity. It is not a cure and it does not work for everyone. But there does seem to be a substantial portion of people who do respond well to it.
Another positive about the anti-CGRP antibodies is that the whole class of drugs is very well tolerated. These treatments are injected and there may be some injection site reactions, but they don’t have many of the side effects that are associated with conventional preventive medications such as cognitive slowing, fatigue, dizziness, weight gain etc.
Anti-CGRP antibodies for migraine also tend to work quickly. Clinicians are seeing a response often within a month for those patients in whom it helps. This is significantly faster than traditional preventatives, which often take weeks or months before they deliver their therapeutic benefits.
There is also a standard dose for these anti-CGRP antibodies. There is usually just one or two doses available for the treatment, which keeps things simple.
At the time of writing (2019), Aimovig has applied to the PBS and been rejected twice. Most recently it has withdrawn permanently from a PBS application.
Emgality (galcanezumab) received a PBS recommendation in late 2019 with some conditions attached. These conditions relate to government cost controls. Currently negotiations are ongoing between the Australian Department of Health and the manufacturer to come to an arrangement. It is not yet confirmed when Emgality will be made available.
The third CGRP antibody is Ajovy (fremanezumab). Ajovy is also a little bit different from the other two in that it has options for monthly and quarterly dosing. The other two are available as monthly injections. Ajovy is in the process of negotiations with the Australian government after a positive recommendation with conditions from the PBS however availability is not yet confirmed.
Neurostimulation is another form of preventative treatment that has recently emerged in the last few years as a potential option for migraine patients. Neurostimulators target certain nerves or parts of the brain that we think are involved in migraine. They act by modulating or modifying the pain system through electrical currents or magnetic impulses.
At the moment there are three options that have been developed and are available to varying degrees.
- Transcranial supraorbital stimulation – Cefaly
- Noninvasive vagal nerve stimulation – gammaCore
- Transcranial magnetic stimulation – eNeura
The Cefaly device is a transcranial supraorbital stimulation device. It looks like a tiara or head band that you wear on the forehead, and acts on the supraorbital nerve.
This nerve is a branch of the trigeminal nerve, which is believed to be involved in migraine. The Cefaly device has at least one well controlled, well designed study that shows a decrease in headache days in patients with “episodic” migraine. There is some suggestion that it might be helpful for people with “chronic” migraine as well, but the evidence is not as strong.
The next option is the vagal nerve stimulator, which is the gammaCore device. Again, it has been studied for chronic migraine but in open label trials (not placebo controlled). To date, the results have not been as strong as other treatment options. It is possible that it might be helpful in reducing frequency and severity in patients with chronic migraine, but definitive evidence of that does not exist yet.
Transcranial Magnetic Stimulation
Transcranial magnetic stimulation works by possibly decreasing a process called cortical spreading depression which is believed to be the mechanism behind migraine with aura. This potentially has a role in migraine prevention as well as possibly acute treatment for migraine with aura. To date, unfortunately, we don’t have very strong evidence for this yet.
All three devices seem to be very safe and well tolerated. These devices are therefore something that may be considered for patients who are unable to take or tolerate any of the other options. The devices may also be beneficial to consider as an adjunct to other preventive treatments. For example, if a patient is taking a medicinal preventive and also uses a device or alternative treatment then they may enjoy better results than if they were employing only one treatment individually.
Complementary And Alternative Treatments
There are complementary and alternative options that can be helpful for migraine. These include:
- Behavioural Treatments
- Cognitive Behavioural Therapy (CBT)
- Relaxation Therapy
- Mindfulness Meditation
- Riboflavin (Vitamin B2)
- Coenzyme Q10 (CoQ10)
There is increasing evidence for some behavioural treatments, particularly CBT, relaxation therapy and mindfulness meditation. These behavioural treatments help patients better understand their response to the migraine and stress itself. It allows people to have more control over their migraine condition by increasing self awareness and control over the mind-body connection.
Biofeedback is a process by which people are able to assess their stress response and then learn ways and mechanisms to regulate it. It also has some good evidence.
There is evidence to support some nutraceuticals and supplements for migraine, in particular magnesium, riboflavin and CoQ10. All of these have been shown in small studies to reduce migraine frequency when used as a daily preventative.
Melatonin can also be helpful as well.
Acupuncture has been shown to be beneficial. Initially there was some suggestion that sham acupuncture is just as effective as true acupuncture, but more recent studies indicate that true acupuncture is more effective than sham acupuncture. We are finding that many patients respond well to this, particularly with treatment over a duration of at least a few months.
Migraine prevention is an important part of any individual’s treatment plan if they are experiencing frequent and disabling attacks. Prevention does not always involve a medicinal drug. Prevention may involve lifestyle modifications, injectables such as Botox or anti-CGRP antibodies, neurostimulation devices and complementary or alternative treatments.
Newer treatments such as Botox and CGRP antibodies have been shown to be safe and effective. However, in Australia these may require several attempts using older medications first. These earlier treatments were often designed for other conditions such as epilepsy or depression and may be associated with side effects.
Once an effective preventive has been found with tolerable side effects it may be combined with lifestyle modifications and complementary or alternative treatments such as CBT, biofeedback or nutraceuticals, to further improve the reduction in migraine frequency and severity