New Preventive Treatments 2021

New Preventive Treatments 2021

Preventive treatments are an important part of migraine management, particularly for people with chronic migraine. In recent years, a number of new preventive treatments have become available which have revolutionised migraine treatment. This article includes the latest updates on preventive treatments, from September 2021.

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Medically reviewed by Dr Richard Stark. Last updated November 30, 2021.

Key points

  • Migraine is more than just a headache. It is a complex neurological disorder, and can be debilitating in some cases.
  • Treatment typically involves a combination of trigger management, lifestyle changes, acute medications, and preventive treatments.
  • ‘Prophylaxis’ is a medical term for preventive treatment.
  • There is no absolute cure for migraine. The goal of preventive treatment is to reduce the frequency and severity of migraine attacks as much as possible.
  • Preventive treatments are not ‘one size fits all’. They affect people differently depending on the person’s medical history and migraine characteristics.
  • There are some exciting new treatments which are effective and don’t have many side effects – meaning they can be used by more people.
  • The most promising new treatments are CGRP antibodies and Botox for migraine.

Watch the full webinar recording

This article was adapted from a webinar by Dr Richard Stark, originally presented during Migraine & Headache Awareness Week 2021.

As Deputy Director of Neurology for Alfred Health, A/Prof Stark has helped to change the way patients with headaches are treated.

He is the President of the Australian and New Zeland Headache Society (ANZHS). He has held leadership positions in the Australian and New Zealand Association of Neurologists and at the World Federation of Neurologists, where he is active in sharing knowledge and supporting young neurologists’ training. He is also a Trustee and Treasurer of the World Federation of Neurologists.

Dr. Stark has had more than 50 articles published, including recent reviews on migraine management in Australia. He has a busy practice in Melbourne which deals predominantly with difficult-to-manage headache and has extensive experience in managing chronic migraine.

Closed captions (CC) or subtitles are available on this video. To activate CC, click on the CC icon next in the bottom right corner of the video player and select “English”. Playback speed and video quality can also be adjusted using the video settings (the icon that looks like a “cog” next to CC icon).

When are preventive treatments used?

Preventive treatments are used when migraine attacks begin to significantly disrupt someone’s day-to-day life. Typically, this will be when people have four or more migraine days per month (1). In other cases, people may have fewer attacks, but when they occur they are so disabling that it warrants being on a preventive treatment.

Some other approaches towards migraine management include lifestyle modifications (to manage triggers) or acute medications (used at the onset of a migraine attack to reduce symptoms). 

These strategies can be sufficient for people who only have the occasional migraine. However, they aren’t always effective enough for people with chronic migraine – and can even be counterproductive. This is because of medication overuse headache (MOH) or rebound headache, which can occur when people are taking acute treatments very frequently. Once the body becomes used to those medications, the withdrawal can be enough to trigger the next headache. That then gets treated with more medication, creating a cycle of increasing medication use and chronic migraine attacks. 

The risk of MOH is one of the reasons that it’s important for people with frequent migraine to find effective preventive treatments.

What options are available?

Most migraine preventives were developed for other conditions (like high blood pressure, seizures, or depression) and were only incidentally found to be helpful for migraine. These can be effective for some people, but it varies from person-to-person. The only treatments to be designed specifically for migraine prevention are CGRP antibodies.

Type of preventiveExamples
Traditional first line therapiesPropranolol, pizotifen, amitriptyline
Older second line therapiesValproate, cyproheptadine, clonidine, verapamil
Newer oral therapiesTopiramate, candesartan, lamotrigine
“Natural” remediesMagnesium, Vitamin B2, Feverfew etc
New InjectablesBotox, CGRP antibodies
NeurostimulationCefaly, springTMS, Nerivio
Percentage of people using preventive medication (graph)
Source: Stark RJ, Valenti L, Miller GC. Management of migraine in Australian general practice. Medical Journal of Australia 2007; 187:142-146.

There weren’t as many medications available in previous decades, with doctors mostly using pizotifen (Sandomigran) or propranolol (Inderal). Even these medications appear to have been underutilised – a 2007 study showed only 20-25% of people with frequent migraine were taking preventive treatment.

Thankfully, we now have many different options for preventive treatment of migraine. A poll during Migraine & Headache Awareness Week 2021 showed that 54% of attendees had tried a preventive medication. Naturally, the people attending a presentation on new preventive treatments are a specific audience – but the variety of new medications provide promising options for people with migraine.

General principles of preventive treatment

When you are thinking about starting preventive treatment, these are some general principles that you (and your health professional) should both keep in mind:

  • It’s a balancing act. Weigh up the benefits against the adverse effects. Don’t just consider the migraine days – it’s important to consider side effects, your lifestyle, your emotional response, and more.
  • Benefits tend to be cumulative. Most people experience fewer migraine days the longer they are taking medication. Unfortunately, many people do not continue taking their medication for long enough to see the effects.
  • Benefits tend to be dose-related. A higher dose will often be more effective in reducing migraine days, but there is a higher risk of experiencing side effects.
  • Many patients are anxious about side effects. It’s true that there are a lot of potential side effects, but there is also a lot of research into these drugs. Your physician should be able to help you avoid any obviously inappropriate treatments, based on your medical history or pre-existing conditions.

Unfortunately, in many cases you won’t know what works until you try it. But these principles can help you make informed choices about your treatment, and realistically assess the effectiveness of a medication.

Common problems: why do migraine preventives sometimes fail?

Side effects

The graph below illustrates the fact that there are a lot of different medications for different people. All of them have some associated side effects, but usually, those are manageable. The most important thing is to make sure you don’t give the wrong medication to the wrong person.

Type of preventiveGeneric nameTrade nameMain problems
Beta blockersPropranolol / metoprololInderal / BetalocAsthma, Raynaud's
Other more selective beta blockers may be less effective (evidence is equivocal).
Serotonin antagonistsPizotifenSandomigranWeight gain, drowsiness
MethysergideDeserilRetroperitoneal fibrosis (unavailable)
AnticonvulsantsValproateEpilimWeight gain, hair loss, lethargy
TopiramateTopamaxReduced appetite, drowsiness, tingle, dysphasia
LamotrigineLamictalOnly for migraine with aura, rash
PregabalinLyricaVery little data
GabapentinNeurontinVery little data (except some in chronic migraine)
Calcium channel blockersVerapamilIsoptinLimited efficacy
FlunarizineSibelliumNot available everywhere. Weight gain, dry mouth.
Other anti-histaminesClonidineCatapresLimited efficacy
CandesartanAtacandHigh dose required, drops blood pressure.
TricyclicsAmitriptyline / nortriptylineEndep / AllegronDry mouth, drowsiness, weight gain.
MAOIs (monoamine oxidase inhibitors)PhenelzineNardilCheese effect (acute hypertension attack)
SSRIs (selective serotonin reuptake inhibitors)Little evidence of efficacy
OtherBotulinum toxinBotoxLimited to chronic migraine
SupplementsMagnesium, vitamins, etc.Limited efficacy
Nerve stimulatorsCefalyExpensive

For example, pizotifen (Sandomigran) is one of the most common preventive migraine medications. In high doses it can cause drowsiness, but most people gradually increase the dosage and take it at night, so that isn’t a major problem. However another side effect is weight gain, so people who have been struggling with their weight find this difficult to use. Another one is propranolol (Inderal) or beta blockers, which tend to make asthma worse. Even if people aren’t currently struggling with their weight or experiencing asthma attacks, their doctor usually won’t prescribe those medications. There’s a risk that it could trigger past health problems, or exacerbate current ones.

Of course, people who haven’t had these health issues could probably use these medications without any trouble – and could find them very effective. This is why it’s important to discuss your full medical history with your doctor, so they can recommend an appropriate treatment.

Past treatments weren’t tolerated

When you’ve tried preventive treatments in the past and not been able to tolerate them, it can be daunting to try something new. 

In these scenarios it’s important to talk everything through with your doctor, and pin down the details of what happened in the past treatment you tried. Your doctor might ask:

  • What dosage were you on?
  • How long were you on it?
  • What else have you tried in the past?
  • Which side effects did you experience?

They might have other questions depending on your medical history. 

If you have had bad experiences in the past and are concerned about side effects that you’ve read about, keep in mind that these lists are only potential side effects. In most cases, they only occur in a small proportion of patients, and you will only experience one or two of the side effects. The lists on medication information leaflets can be long, but a conversation with your doctor can clarify what to expect. 

Treatment isn’t working

Sometimes, treatments just don’t work. But in other cases, people might just not have tried it for long enough. A study in the United States shows that less than a quarter of patients were still taking their medication after one year.

Graph of how many people stop taking medication
Source: Hepp Z, et al. Cephalalgia. 2017;37:470-485.

While some of those people may have had unacceptable side effects, there is also a huge issue with compliance in migraine prevention. It’s hard to take medication every day, particularly if it needs to be twice a day or at the exact same time. Unfortunately, if the medication isn’t taken as directed, it might not work. You can speak to your doctor about strategies to improve this, whether that’s setting an alarm or keeping your medication next to your toothbrush. 

This is one of the major advantages of the new injectable treatments, which only need to be administered every 1-3 months. If you have a very busy work or life routine, it can be almost impossible to take medication on a perfect schedule, so these are a much better alternative.

In summary

Table summarising common problems & solutions in migraine prevention.

New preventive treatments

Recently, there have been a number of new preventive treatments which have transformed migraine management. There are some oral therapies which aren’t brand new, but they are relatively under-prescribed compared to older medications. However, when discussing new treatments, most of the conversation has been around botulinum toxin (Botox) and the CGRP antibodies. 

These medications are clearly effective, and the good news is that they are safe. The studies so far have been remarkably free of troublesome side effects. Compliance is also much less of an issue, because patients don’t need to get the injections too frequently.

On the other hand, these treatments are all intrinsically expensive. Fortunately, we now have PBS approval for Botox and for two of the CGRP antibodies. When considering these medications, it’s important to be aware of the PBS criteria as there are some restrictions to access the subsidised costs. The criteria are:

  1. You need a new prescription from a neurologist (not a general practitioner).
  2. Chronic migraine diagnosis (15 or more headache days per month).
  3. You have tried and failed at least three standard treatments before. 
  4. You do not have medication overuse headache.
  5. You are over 18.

If you think you qualify for these criteria, you can keep a headache diary to show your doctor. A headache diary is a great way to confirm your diagnosis and help your doctor understand the full extent of how migraine is affecting you.

Preventive oral therapies

Preventive oral therapies include topiramate, candesartan, and lamotrigine. Topiramate and lamotrigine were originally developed as anticonvulsants, and candesartan as a medication for high blood pressure.

In the graph about topiramate (in the image carousel below), you can see how effective different doses are over time. As discussed in the principles of migraine prevention, this shows that the benefits are cumulative and dose-related. While all doses from 50, 100, or 200 milligrams were effective, the highest dose was the most effective. This is the case for many preventive medications.

However, the higher the dose, the more likely people are to get side effects. There are some people who can tolerate the high dose, and it works well for them. In other cases people will get side effects even with a moderate dose, but get a good response from the low dose. It’s an individualised process, and you should let your doctor know about any concerns to ensure you’re on the best dose for your body.

Candesartan is still relatively underused in migraine treatment, but it can be very useful. It is well-tolerated by most people which is good for patients who have had negative experiences with other preventives. 

Lamotrigine is a bit different. It is only really effective for people who get visual aura (or other aura symptoms) as a prominent part of their migraine. They do very well on lamotrigine, as shown in the third slide of the image carousel below. You can navigate between the graphs using the arrows, or the three dots underneath the image.

Botulinum toxin (Botox)

Botox isn’t just a cosmetic treatment, it has become an effective treatment for patients with chronic migraine (over 15 headache days per month). 

As a prophylactic treatment for migraine, Botox is injected at 31 different sites in the head and neck area. These specific sites are over the major sensory nerves in your head. It’s important that the treatment gets taken up by your nerves, because this is what makes it work.

Graph of Botox injection sites for migraine prevention.
Source: Schuenke M et a., eds. Theime Atlas of Anatomy: Head and Neuroanatomy. Stuttgart: Thieme; 2010.

When Botox gets into the nerve terminals, it prevents the release of various chemicals. For cosmetic injections, the treatment stops the release of acetylcholine, which affects your muscle fibres. For migraine treatment, the injections target the sensory nerves, reducing the release of various chemicals from those pain fibres (including CGRP).

There is a lot of evidence that Botox works well for migraine. The benefits have been reported by doctors in the patients they treat, and demonstrated in a number of clinical trials. Many people find that Botox reduces both the severity and frequency of their migraine attacks.

Graph showing the effectiveness of Botox as a migraine preventive.

Read the full article on Botox for Migraine.

CGRP antibodies

The CGRP antibodies are the first medication to be developed specifically for migraine treatment. While Botox only works well for chronic migraine patients, CGRPs can be effective for both chronic and episodic types. Some research studies also included people with medication overuse headache, and the results showed that CGRPs can help with MOH, too.

Current CGRPs available in Australia

DrugBrand nameAvailability
GalcanezumabEmgalityPBS listed (June '21)
FremanezumabAjovyPBS listed (August '21)
ErenumabAimovigTGA approved
Available privately
EptinezumabVyeptiTGA approved
Available privately

Visit our new treatment updates page to see the latest information on CGRP approvals and how to access these medications.

So how do CGRPs work? 

First, we need to understand what calcitonin gene-related peptides actually are, and how they work:

  • CGRP is a 37-amino acid neuropeptide encoded by the calcitonin gene. A neuropeptide is a type of chemical messenger that regulates neural function.
  • It is widely distributed in both the central and peripheral nervous systems (i.e. in your brain, and in nerves throughout your body).
  • It is present in nerves in the trigeminal system, and we know these nerves are sensitised during migraine attacks.

When the trigeminal nerve is activated, CGRP is released – so during a migraine attack, CGRP levels are higher. Research has found that blocking this chemical can help manage migraine for many patients.

Diagram of where CGRP is found in a migraine attack.

There are two ways to block CGRP. Aimovig is an antibody that attaches to CGRP receptors, while Emgality, Ajovy, and Vyepti are all antibodies that attach to the CGRP molecule itself. Either way, the end result is the same: it prevents the molecule from connecting with the receptor and activating the sensory fibers that cause pain. 

These medications have been incredibly effective, and have made a big difference for how we can manage migraine. Like any medication, it is true that they don’t work for everyone. However, the response rates and lack of side effects are still good in comparison to traditional therapies. 

The graph below shows the effectiveness of the different CGRP medications. This shows the percentage of people that had more than a 50% reduction in migraine attacks – a life changing result for many people living with migraine.

Graph of CGRP effectiveness

Source: Smith J, et al. Headache. 2017:57 Suppl 3:130; b. Tepper S, et al. Lancet Neurol. 2017;16:425-434; c. Detke HC, et al. Cephalalgia. 2017;37:338; d. Silberstein SD, et al. N Engl J Med. 2017;377:2113-2122.

Read the full article on CGRP medications.


Neuromodulation devices are another one of the new preventive treatments. There are various ways to stimulate nerves around the head and neck area, which can make a difference to the way migraine behaves. The key nerves are:

  • Supraorbital nerves (above the eyes), which can be stimulated with a device.
  • Vagus nerve (in the neck), a newer method.
  • Occipital nerve (back of the head), used less frequently because it generally requires planting an electrode.

The Cefaly device stimulates the supraorbital nerves, and there is evidence that this device works. Researchers developed a trial that allowed them to compare the real device to a placebo device, and 38% of people receiving the real treatment experienced more than a 50% reduction in headache days. The full results of the study are below.

Graph showing the effectiveness of Cefaly as a preventive treatment.
Graph showing effectiveness of Gammacore device for migraine prevention
Source: Stephen D. Silberstein et al. Neurology 2016;87:529-538

When Cefaly was introduced as a treatment, it was provided on a rental basis for a month or two, so that patients could decide whether they would buy it or return it. The results of this also showed that many people found it effective – out of 2,313 patients, 53% of people chose to buy the device. There were also very few reported side effects. 2% of people experienced skin pain, and only 0.1% had an allergic reaction.

The GammaCore device stimulates the vagus nerve. It is used for migraine and can also be effective to treat cluster headache, which is a very difficult headache type to treat. The graph above (right) shows the results of an 8 month trial. Once again, not everyone found it effective, so some people dropped out. But others continued to find it helpful, and used it for the full trial period.

These devices are attractive to some people because they aren’t a drug, and don’t carry the usual drug-related side effects. This is important during pregnancy, for example, when people are anxious about using other medications.

Medication overuse headache

Medication overuse headache (MOH) is an important consideration for people who are getting frequent migraine attacks. Certain acute migraine medications can be troublesome, to varying degrees.

Diagram illustrating the risk of different medication types for overuse headache.

Medications that include opioids (morphine- or codeine-related compounds), are particularly concerning for MOH. The triptans (Imigran, Zomig, Naramig, Maxalt, Relpax) can also cause MOH, but they’re not as high risk as the codeine-based medications. Simple analgesics and anti-inflammatories are much less of a problem, but occasionally can lead to MOH.

Generally, physicians advise using anti-inflammatories, with occasional triptans, for acute migraine treatment.

The maximum dosage guidelines for each medication are:

  • Simple analgesics/NSAIDs – 3-4 days per week
  • Triptans – 1-2 days per week
  • Ergotamines – never
  • Codeine – never, or once a month (if necessary)
  • Injected narcotics – once every couple of months (if necessary)

Menstrual migraine

Migraine in women is often influenced by hormones. Some women don’t get migraine attacks at all, except around the time of menstruation. In these cases, women have the option to use “mini-prophylaxis” methods rather than taking a constant preventive treatment.

Mini-prophylaxis is when you just take medication over the time that you are vulnerable, as shown below.

Diagram of different types of mini-prophylaxis for menstrual migraine.
Source: Silberstein S et al. Neurology 2012;78:1346–53

Frovatriptan is not available in Australia – the longest-acting triptan we have here is naratriptan, so that can sometimes be used instead. Naproxen is an anti-inflammatory pain medication, whereas estradiol gel contains estrogen to regulate hormone levels.

These treatments all begin just before menstruation. For mini-prophylaxis to be effective, women need to have a regular menstrual cycle, and know that migraine predominantly occurs at the same time during menstruation. Unfortunately, this preventive method isn’t effective for people with irregular cycles or migraine attacks. 

Read the full article on Hormonal Factors in Migraine for more information about menstrual migraine.

Take home messages

  • Migraine is under-recognised and under-treated in the community
  • Treatment can include a combination of lifestyle changes, acute treatments, and preventive treatment
  • There are many options for preventive treatments – some are older, some are newly developed, and some new treatments are just existing medications being repurposed
  • Being aware of potential side effects and reasons that people might be reluctant to use a preventive treatment is essential
  • Botox and CGRPs have revolutionised the treatment of chronic migraine
  • Neurostimulation is a promising option
  • Specific approaches are used for MOH and menstrual migraine

Further information and resources

This article was adapted from Dr Richard Stark’s presentation during Migraine & Headache Awareness Week 2021 and has been medically reviewed. You can view the video of this presentation, and the other presentations from the week, on our webinar recordings page.

If you’d like to learn more about preventive treatments or strategies discussed in this article, you can view the following articles and webinars:

Here are some further resources about migraine in general, and other treatment options or management strategies to explore.


  1. Dr. Richard Stark. Migraine & Headache Awareness Week Webinar Presentation. Sept 2021.

Headache AustralianMigraine & Headache Australia is the only organization in Australia that aims to support the more than 5 million Australians affected by headache and migraine.