Migraine is primarily a headache disorder, but there are many symptoms associated with the condition and they are frequently debilitating. In the UK, there is an estimated 190000 attacks per day and 25 million lost workdays per year (Steiner et al, 2003).
Acute or episodic migraine
In acute migraine, the episode lasts 4–72 hours. There is usually a prodromal period prior to the headache that might consist of symptoms such as irritability, tiredness, dizziness, hunger, nausea, or yawning, followed by an often-unilateral headache and, sometimes, aura, such as tingling and visual and speech disturbance. A recovery period, which can last up to a few days, will then take place, followed by a clear period with no symptoms (Johns Hopkins Medicine, 2021).
Despite being episodic, acute migraine is debilitating, and, while two episodes per month will not be classified as chronic migraine, it can still have a dramatic effect on a patient's life. Research into the effects of botulinum toxin on these conditions is mainly focused on chronic migraine syndrome. However, patients with frequent acute migraine attacks who do not fulfil the criteria for chronic migraine may benefit from botulinum toxin treatment, although specific evidence for this is not currently available.
Chronic migraine
The National Institute for Health and Care Excellence (NICE) guidance, in accordance with the International Headache Society, defines chronic migraine as:
‘The occurrence of headaches on 15 days or more per month, for at least 3 months, where the attacks fulfil criteria for pain and associated symptoms of migraine. This must be without aura on at least 8 days per month for at least 3 months, where there is no medication overuse, and where the headaches are not attributable to another causative disorder. To fulfil the criteria for chronic migraine, a person must previously have had at least five attacks fulfilling the International Headache Society's criteria for migraine without aura. Despite these criteria, in clinical practice, there is a lack of consensus regarding the definition of chronic migraine.
Using toxin to treat migraine
Migraine has a complicated pathophysiology with many unknown areas. Complex neurochemical changes create migraine headaches, and it has a strong genetic element (Dodick, 2018). Botulinum toxin does not work in chronic migraine by muscle relaxation, but, rather, the reduction of pain pathway expression in certain parts of the trigeminal system (Burstein et al, 2014).
Botulinum toxin is licensed for use in chronic migraine, is recommended by NICE and can be used in the NHS within criteria that are locally determined and it is invariably accessed via secondary care contracts. NICE suggests that it may be an appropriate treatment for chronic migraine in patients who have not responded to at least three prior pharmacological prophylaxis therapies and whose condition is appropriately managed for medication overuse (NICE, 2012). NICE guidance is generally used as a benchmark for local criteria-based patient selection.
Botulinum toxin does not work in chronic migraine by muscle relaxation, but, rather, the reduction of pain pathway expression in certain parts of the trigeminal system
NHS treatment of migraine with botulinum toxin usually follows NICE guidance, which states that three prophylactic drugs need to have been tried before botulinum toxin is offered to a patient (NICE, 2012). NHS wait times and increasing challenges have resulted in patients not being commenced on botulinum toxin or having their treatment programmes interrupted. In private practice, the decision to treat a patient is between the clinician and patient and is based on clinical evaluation. Provided that the diagnosis is correct and red flags have been excluded, it is reasonable to start treatment. However, it should be noted that good communication with a patient's GP is important and considered good practice. The author suggests writing to the patient's GP to inform them that the patient has undergone migraine treatment with botulinum toxin, providing details of the number of units used.
Consultation
Patients may present at clinics for a variety of reasons. Some do not have a diagnosis but believe they have chronic migraine. The reasons behind their thinking should be explored. Some patients will have typical chronic migraine but, with the myriad of possible symptoms, it is sometimes unclear who has the disorder. Dealing with these patients creates dilemmas. Clinicians may decide to only treat those with a formal diagnosis, or some may be happy to proceed based on their own assessment. It is important to openly discuss with the patient that, if they do not have chronic migraine, botulinum toxin treatment is more likely to be ineffective. They may still wish to proceed on this basis. Many patients are disheartened and will try anything to gain some relief. It is reasonable to have a trial of treatment on this basis, provided that the clinician is not making false promises to the patient about treatment outcomes.
Other patients may be awaiting NHS treatment but do not want to wait any longer and would rather pay than wait. Some patients have had NHS treatment, but it may have been cancelled or delayed.
» There is a small subgroup of patients (around 10%) who fail to respond to first-line treatment, but research has shown that they will respond after two cycles of treatment at 3 months «
Treatment with botulinum toxin outside of chronic migraine is off-licence and needs to be managed as such. This includes a frank discussion with the patient about what this means. Consent should include this, and it should be recorded. When consulting a patient, it is important to conduct a proper medical history. To do this thoroughly, there are some important issues that need to be considered. First, find out whether the patient in question has received a formal diagnosis of chronic migraine, by whom and when. Then, the clinician should ask what previous treatments the patient has had (if any). The author also often checks which prophylactic medications they have had, their doses and the duration of trial and side effects.
It is important to look for drugs that might precipitate migraine, such as oestrogen and nitrates, as these might just need to be stopped to solve the problem (National Migraine Centre, 2021). At this point, it is important to liaise with the patient's GP to ascertain the patient's main migraine triggers. For example, common migraine triggers include stress, dehydration, caffeine, alcohol, too much or too little sleep, certain foods, such as chocolate, citrus fruits and cured meats, and hormonal changes (NHS, 2021). As triggers are personal to each patient, it is essential for a diary to be kept, because this provides vital clues that aid management. Even if a patient is treated with botulinum toxin, identifying triggers and reducing them will help to further reduce attacks.
Finally, ensure to check for warning signs that may indicate that the problem is something else, especially if the patient has not been to a specialist prior to visiting an aesthetic clinic (Kochhar, 2018), for example, headaches that occur in patients over the age of 50 years that were not present before. Most people who experience migraine have had headaches since puberty or even before and follow a certain pattern that might change slowly over time. Worsening symptoms are also a sign that there may be something more serious causing the headaches. In these cases, migraines can be mistaken for thunderclap headaches, which are sudden-onset severe headaches that raise suspicion of sub-arachnoid bleeds. Similarly, symptoms of temporal arteritis can appear alike to a migraine, with a unilateral temporal tenderness, headache and visual disturbance. However, this generally occurs in people aged over 50 years, and the headache pattern will be different to a patient's migraine, or they may have no pre-existing migraine. Glaucoma symptoms, which predominantly include eye pain and redness of the eye, may also mimic a migraine, and any additional neurological symptoms, including meningism, are concerning (Gooriah and Ahmed, 2015).
Treatment approach
In 2009, pharmaceutical company Allergan conducted seminal research into the use of botulinum toxin in migraines. After 12 months, onabotulinum toxin A treatment at 3-monthly intervals, the phase 3 research evaluating migraine prophylaxis therapy (PREEMPT) trials showed that 70% of patients had a greater than 50% reduction of headaches, with minimal side effects (Dodick et al, 2010).
The PREEMPT protocol is 31 injections in the head and neck, with a total of 155 units of botulinum toxin used. There is the option of a further 40 units to be administered in the occipitalis, temporalis and trapezius areas if required (Dodick et al, 2010).
Treatment protocols are generally based upon the PREEMPT trials, which were methodologically robust (Dodick, 2018). However, there are criticisms of the PREEMPT trials. These mainly concern the marked placebo effect in both PREEMPT trials and the fact that most patients enrolled were overusing acute migraine medications (Gooriah and Ahmed, 2015).
A survey by Begasse de Dhaem et al (2020) suggested that approximately 70% of clinicians varied the dose, sites and frequency of the toxin injections. Therefore, it would be interesting to explore the reasons behind this and develop new guidance as a result.
There is a small subgroup of patients (around 10%) who fail to respond to first-line treatment, but research has shown that they will respond after two cycles of treatment at 3 months (Aurora et al, 2011). Therefore, it is worth trying three cycles before ceasing treatment altogether. Doses should be at least 155 units of botulinum toxin, as earlier trials showed minimal difference from placebo below this dose (Dodick, 2018). Additionally, it is often worth treating trigger points and increasing the dose up to 195 units (Gooriah and Ahmed, 2015).
Herd et al's (2019) meta-analysis of the use of botulinum toxin in migraine showed that it reduced headache by 2 days per month in chronic migraine. However, it included some overuse headache patients, so does not confirm or refute the effect of botulinum toxin on episodic migraine. The review found it to have a favourable safety profile (Herd et al, 2019).
There is a lack of consensus about treatment intervals. The author suggests starting a patient on two cycles of treatment with 12-week intervals and reviewing at 24 weeks. If there is no response, it is less likely that they will respond to further treatments, but clinicians can explain that there are 10% of patients who may respond to a third treatment. The patient can then choose how they wish to proceed. If it is effective, full treatment is likely to be required three or four times per year.
The side effects of botulinum toxin treatment are minimal. Brow ptosis can occur, but this is less likely in aesthetic practices, as clinicians are aware of this complication and may adjust the distribution of the injections as a result. Anecdotally, no issue regarding altering the distribution of injections in this site has been found.
There have been trials comparing prophylactic migraine medications to botulinum toxin, and they found them to be comparable (Magalhaes et al 2010; Cady et al, 2011). However, these studies are small.
Other toxins, such as Bocouture and Azzalure, can be used off label, but different units will need to be used and adjusted, for example, where 1U Bocouture is equal to 2.5U Azzalure (Blatchley, 2016).
Setting up a service
Treatment of chronic migraine with botulinum toxin is a specialised service. It is best suited to a Care Quality Commsission (CQC)-registered clinic. Aesthetic clinicians will be well versed in the effects of toxin on the face and handling the product. This treatment is available on the NHS, but it can be quite difficult to obtain, hence patients may seek the help of aesthetic clinics. The author suggests undergoing formal training in the technique, which is not easy to find but, with research, suitable courses can be identified. Once certificated, clinicians need to inform insurers before undertaking any treatments.
Setting up the service is relatively simple, as it only requires a treatment protocol, consent forms and the usual equipment for administrating botulinum toxin.
Pricing of the treatment is a question of making calculations around the costs. If you allow for 200 units of botulinum toxin for a single treatment cycle, that should be generous and ensure that costs are covered for the toxin. It is an expensive treatment due to the quantity of toxin required and the time needed to assess the patient. Repeat treatments require less clinician time and the cost can be reduced. As with many treatments, it is better to underpromise and overdeliver, which is why the author recommends being guarded about treatment outcomes. That being said, there is good clinical evidence that, with correct patient selection, significant life-changing improvements can be made.
Summary
Botulinum toxin is licensed for use in treating chronic migraine. The key elements of optimal treatment are ensuring appropriate patient selection, correct technique, identifying and minimising triggers, good liaison with the patient's GP and correct aftercare. It must be stressed that not all chronic migraineurs respond to botulinum toxin, so patient expectations need to be realistic and will need exploration at the initial consultation. Overall, treatment with botulinum toxin appears to be a safe method with long-term tolerability.
Key points
- Botulinum toxin is licensed for chronic migraine treatment
- Treatment is safe and effective in reducing headache frequency
- According to research, protocols for treatment are varied by individual clinicians
- Treatment should only be carried out by suitably qualified clinicians and in the correct setting.
CPD reflective questions
- What is the average required dose of botulinum toxin?
- Do all clinicians inject the same points when using botulinum toxin for migraine?