Dr David Watson and Dr Sandeep Sharma provide an overview of the recommendations from the latest SIGN guidance on managing migraine

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Dr David Watson

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Read this article to learn more about:

  • why a new guideline on migraine was necessary
  • acute and preventative treatments for migraine
  • treating medication overuse headache.

Key points

Implementation actions for STPs and ICSs

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Migraine is the most common severe form of primary headache (a headache that is not associated with an underlying pathology), with a global prevalence of around one in seven people.1 Data from the Landmark study revealed that, of patients attending general practice with episodic disabling headache, 94% had migraine.2 In the age group 15–49 years, migraine is the top cause of years lived with disability.3

Need for a guideline

In 2008, SIGN published its first guideline on headache: SIGN 107 on Diagnosis and management of headache in adults, which included a section dedicated to migraine.4 Since 2008, chronic migraine has been redefined, new evidence on acute and preventative therapies has become available (botulinum toxin A is now licensed to treat chronic migraine),5 and there is an overall greater understanding about the pathophysiology of migraine. Medication overuse headache (MOH) has become better recognised, and guidance on its management is necessary.

Despite a plethora of guidelines available, evidence suggests that migraine is still under-diagnosed and poorly managed. A cross-sectional study of 10 European countries showed that, in most, fewer than 10% of patients with frequent migraine were receiving adequate acute therapy and even fewer received preventer therapy, despite being eligible.6 It is likely that the situation is similar in the UK.7

In February 2018, SIGN published SIGN 155 on Pharmacological management of migraine,8 which supersedes the recommendations on migraine in SIGN 107. The 2018 guideline focuses on treatment for adults with acute migraine and preventative treatment for adults with episodic migraine, chronic migraine, or MOH, with the aim of improving quality of care and patient outcomes.

Diagnosis of migraine

Accurate diagnosis of migraine is the key to successful treatment. Diagnosis should be made using the International Classification of Headache Disorders diagnostic criteria (see: ichd-3.org/classification-outline). Practitioners should refer to the definitions of migraine without aura, chronic migraine, and medication overuse headache. Note that in reality, patients may not always meet all the criteria. In a busy general practice, headache diaries can be helpful to quantify the number of headache days and other migraine symptoms. It is useful to ask the patient what they would like to do when they have a headache; most patients with migraine prefer to keep their head still when the pain is bad but may not necessarily lie down. Some patients may have to stop activities. Patients with tension headache, which is featureless, tend not to be disabled so are less likely to consult a doctor. Patients with cluster headache are very disabled by pain and agitation but the headache is short-lived, usually lasting about 1–2 hours (migraine tends to last at least 4 hours if untreated). Headache with a sinus source is rare and most frontal headache will be migraine. It is important to be aware that only about one-third of migraine patients get aura,9 40% will get bilateral pain,9 and at least 50% will get neck pain.10 Dizziness is also common, with a lifetime prevalence of 18%.11

Treatment

Medication for migraine is classified as either acute or preventative.

Acute treatment is used either to abort an attack of migraine or to significantly reduce the severity of the headache and other symptoms. Preventative treatment is taken continuously to reduce the frequency and severity of migraine attacks. Often a combination of acute and preventative treatment is needed.

For treatment to be effective, it is crucial that the correct diagnosis has been made.

Please note that not all of the treatments discussed in this article currently (May 2018) have UK marketing authorisation for the indications mentioned. The prescriber should follow relevant professional guidance, taking full responsibility for all clinical decisions. Informed consent should be obtained and documented. See the General Medical Council’s guidance on Good practice in prescribing and managing medicines and devices12 for further information.

Refer to SIGN 155 for information about treatments in pregnancy.

Acute treatment

Acute treatment works best if it is administered as early as possible in the migraine attack, before central sensitisation of the brain develops.8,13 Once this ‘brain wind-up’ occurs, treatments tend to be less effective. For this reason, patients who wake with a migraine often find it difficult to treat.

SIGN 155 recommends using either simple analgesics (aspirin 900 mg or ibuprofen 400–600 mg) or triptans (sumatriptan 50–100 mg) as first-line treatment. If sumatriptan is prescribed and the response is inadequate, try sequencing through different triptans. Practitioners may also consider prescribing a combination of sumatriptan (50–85 mg) and naproxen (500 mg). Specific points on using triptans are listed in Box 1. Antiemetics (metoclopramide 10 mg or prochloroperazine 10 mg) are recommended for patients who experience symptoms of nausea or vomiting. Both metoclopramide and prochloroperazine have direct analgesic effects and so can be helpful even in patients who have little gastric upset, in combination with simple analgesics or a triptan.8

Box 1: How to use triptans8

  • Triptans only work once the headache starts
    • in patients who have aura (a temporary neurological disturbance that typically gives visual or sensory symptoms), it is recommended that triptans are taken at the start of the headache and not at the start of the aura (unless the aura and headache start at the same time)8,13
  • A repeat dose of triptan can be taken after 2 hours if the first dose had been successful but the headache recurs or gets worse again
  • Patients have a variable response to individual triptans and it is worth sequencing through different triptans to find the most effective one 
  • All orodispersible (dissolve in the mouth) triptans are gastrically absorbed. In patients who vomit early in a migraine attack, nasal and subcutaneous triptans should be considered.5 A significant proportion of the nasal dose is still gastrically absorbed
  • In patients with moderate to severe attacks, combining a triptan with aspirin or a non-steroidal anti-inflammatory drug (NSAID) may be beneficial 
  • Sumatriptan can be considered for treatment of acute migraine in pregnant women in all stages of pregnancy. The risks associated with use should be discussed before commencing treatment
  • It is acceptable to co-prescribe a triptan with a selective serotonin reuptake inhibitor (SSRI) antidepressant as the risk of serotonin syndrome is very small 

Table 1 lists the number needed to treat (NNT) to achieve an outcome of pain free at 2 hours for several acute migraine therapies—note that the list of therapies is not exhaustive. It shows that sumatriptan (administered as a subcutaneous injection) is the most effective treatment, and paracetamol is the least effective. Acute treatment will not always work for every migraine, and patients should be offered appropriate rescue medication for this situation. For example, subcutaneous sumatriptan may be appropriate in some patients who do not respond to an oral or nasal triptan. The risk of MOH should be discussed with every patient started on acute treatment. The algorithm for pharmacological management of migraine, shown in Figure 1, outlines good practice in acute treatment.

There are a number of devices that are marketed as helpful in treating migraine symptoms. The SIGN guideline development group found no robust evidence to make any recommendations for any of them.8

TherapyNNT
Table 1: Calculated numbers needed to treat for acute migraine therapies for an outcome of pain free at 2 hours in patients with moderate to severe pain, compared with placebo8

Simple analgesics

Aspirin 900 mg or 1000 mg

8.1

Diclofenac potassium 50 mg

8.9

Ibuprofen 400 mg

7.2

Ibuprofen 200 mg

9.7

Naproxen 500 mg or 825 mg

11

Paracetamol 1000 mg

12

Oral triptans

Sumatriptan 50 mg

6.1

Sumatriptan 100 mg

4.7

Zolmitriptan 5 mg

4.8

Zolmitriptan 2.5 mg

5.0

Nasal sprays

Sumatriptan 20 mg

4.7

Zolmitriptan 5 mg

3.0

Subcutaneous injection

Sumatriptan 6 mg

2.3

Combination therapy

Sumatriptan 50–85 mg and naproxen 500 mg

4.9

NNT=number needed to treat

Scottish Intercollegiate Guidelines Network (SIGN). Pharmacological management of migraine. SIGN 155. SIGN, 2018. Available at: sign.ac.uk/sign-155-migraine.html

 

Pharmacological management of patients with migraine treatment pathway v2

Figure 1: Pharmacological management of patients with migraine treatment pathway

Source: Scottish Intercollegiate Guidelines Network (SIGN). Pharmacological management of migraine. SIGN 155. SIGN, 2018. Available at: sign.ac.uk/sign-155-migraine.html

Preventative treatment

Regular, preventative medication should be considered for patients with chronic or episodic migraine. The decision to start treatment should be guided by the impact of migraine on the patient’s quality of life, rather than the absolute number of migraines experienced per month. Even modest improvements in the frequency or severity of migraine headaches can provide considerable benefits to an individual; within trials, a reduction in migraine headache severity and/or frequency of 30–50% is regarded as a successful outcome. Guidance on starting and stopping preventer medication is provided in Box 2.

Box 2. Guidance on starting and stopping migraine preventer therapy8

  • Treatment choice depends on patient preference, co-morbidities, evidence of effectiveness, and drug interactions (e.g. caution should be taken using propranolol in asthma and topiramate in depression) 
  • Titrate prophylactic medication to maximum tolerated dose for 3 months before considering treatment failure 
  • Effective prophylaxis should be continued for 6–12 months and then reviewed for continuation
  • Address any medication overuse as this may make prophylaxis less effective 
  • Effective contraception is required before starting any preventer therapy that can potentially harm an unborn baby 
  • Migraine without aura often gets better in pregnancy, so women should aim to stop prophylactic treatment before pregnancy.

SIGN 155 recommends propranolol 80–160 mg daily or topiramate 50–100 mg daily as these medicines have the best evidence base. All medications should be reviewed if pregnancy is planned—topiramate is contraindicated in pregnancy due to the risks to the unborn baby.

If propranolol or topiramate are not tolerated or are contraindicated, other medications that can be considered are:8

  • amitriptyline 25–150 mg at night (or a less sedating tricyclic antidepressant if amitriptyline is not tolerated)
  • candesartan 16 mg daily—it has a good side-effect profile with no potential cognitive effects; however, the evidence base is small and further trials are unlikely to be conducted
  • sodium valproate 400–1500 mg daily—prescribers should be aware that sodium valproate is associated with an increased risk of foetal malformations and poorer cognitive outcomes in children exposed to valproate in utero. Prescribers need to be aware of the current MHRA advice on safe prescribing.14

If treatment with three or more oral prophylactic therapies has failed, botulinum toxin A is recommended for patients with chronic migraine (not episodic migraine), where medication overuse has been addressed.8

It is worth noting that SIGN advises against using gabapentin for the prophylactic treatment of migraine.8

There was insufficient evidence to support a recommendation for:8

  • pizotifen
  • pregabalin
  • SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs)
  • angiotensing-converting enzyme inhibitors.

The only calcium channel blocker with supporting evidence in treating migraine is flunarizine, which is not licensed in the UK. Provision of flunarizine is normally via hospital prescription by a specialist headache service.8

A suggested prophylaxis treatment pathway is included in the algorithm in Figure 1.

Medication overuse headache

Medication overuse headache (MOH) is where frequent use of acute treatments for migraine increases headache intensity and frequency. Most MOH is a complication of migraine.8 The following are accepted causes of MOH:15

  • use of triptans, ergots, combination analgesics and/or opioids on 10 or more days per month
  • use of simple analgesics on 15 or more days per month.

Risk factors for the development of MOH include frequent headache, another painful condition requiring analgesia, and psychiatric co-morbidity. Importantly, not all patients overusing acute treatments have MOH, and some just have poorly treated migraine. Withdrawing the overused medication can reduce headache frequency and intensity, although initially withdrawal is often associated with transient worsening of headache. There is no strong evidence on what the best withdrawal strategy is; Box 3 summarises the options available. The SIGN guidelines states that prednisolone should not be used in the routine management of MOH. Although naproxen is often used in clinical practice as a transitional treatment there is no evidence for its use in patients with MOH. It is important to inform patients about MOH before starting acute treatment.8

Box 3: Medication overuse withdrawal strategies8

The choice of strategy to address medication overuse should be tailored to the individual patient and may be influenced by co-morbidities. Strategies include:

  • abrupt withdrawal alone; preventative treatment may then be considered after a delay
  • abrupt withdrawal and immediately starting preventative treatment
  • starting a preventative treatment without withdrawal.

Consider withdrawing strong opioids gradually.

Barriers to implementation

SIGN 155 provides clear advice on the management of migraine. An accurate diagnosis is essential to manage migraine effectively. Patients are often misdiagnosed as having ‘tension headache’ or ‘sinus headache’ or no diagnosis is given.7,16 General practitioners should be aware of the Landmark study2 mentioned at the outset of this article, which reported that of patients attending GPs with episodic disabling headache, 94% had migraine.2 Barriers to doctors making a diagnosis include lack of formal headache training, lack of confidence in making a diagnosis, and time pressures.7

At the secondary care level, there are only a few neurologists with a headache interest and while numbers of GPwSI in headache are growing (albeit slowly) there are many parts of the UK that do not have a headache service.7 This makes access to therapies such as flunarizine and botulinum toxin difficult for patients.

Conclusion

SIGN 155 provides an evidence-based update on the medical management of migraine. Probably the most useful section for GPs and nurse practitioners is the migraine treatment pathway found in Annex 3 of the guideline, and reproduced in this article (see Figure 1). In summary, if a patient attends general practice with disabling episodic headache they most likely have migraine and should be provided with effective acute therapy and prophylaxis depending on the extent of disability and co-morbidities. See Box 4 for a list of useful sources of information for patients and healthcare professionals.

Box 4: Useful sources of information

Dr David PB Watson

GP partner, Hamilton Medical Group, Aberdeen

GPwSI headache, Department of Neurology, Aberdeen Royal Infirmary

Member of the guideline development group for SIGN 155

Dr Sandeep Sharma

GP, Bonnybridge

Member of the guideline development group for SIGN 155

 

Key points

  • Episodic disabling headache is likely to be migraine
  • Simple analgesics work better if taken at the start of the headache and in high doses, e.g. aspirin 900 mg or ibuprofen 400–600 mg
  • Triptans only work when headache starts, not during aura
  • Melt-in-the-mouth triptans are gastrically absorbed
  • Triptans can be used in pregnancy after counselling on risks
  • Acute therapy should be restricted on average to 2 days a week to reduce the risk of developing medication overuse headache. Do not use opiates for migraine
  • Metoclopramide 10 mg and prochloperazine 10 mg can help nausea and have direct analgesic effects
  • Consider prophylactic treatment if the migraine is disabling, such as frequent or prolonged headache:
    • first choice prophylaxis is propranolol 80–160 mg daily;  topiramate 50–100 mg daily is also recommended. Second choice is a tricyclic antidepressant or candesartan 16 mg daily.

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Publish guidance on the diagnosis and management of migraine in easily located places, such as formulary and referral apps or websites
  • List local cost-effective formulary choices for treatment of acute and chronic migraine
  • Offer and commission local headache referral services though specialists or GPwSIs to support GPs in diagnosis and also treatment of resistant cases
  • Encourage community pharmacy to offer effective advice and over-the-counter medication for patients with migraine, who often present first to them.

STP=sustainability and transformation partnership; ICS=integrated care system

References

  1. Steiner T, Stovner L, Birbeck G. Migraine: the seventh disabler. J Headache Pain 2013; 14 (1): 1.
  2. Tepper S, Dahlof C, Dowson A et al. Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study. Headache 2004; 44 (9): 856–864.
  3. Steiner T, Stovner L, Vos T et al. Migraine is first cause of disability in under 50s: will health politicians now take notice? J Headache Pain 2018; 19 (1): 17.
  4. Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of headache in adults. SIGN 107. SIGN, 2008. Available at: www.sign.ac.uk/sign-107-diagnosis-and-management-of-headache-in-adults.html
  5. British National Formulary. Botulinum toxin type A. bnf.nice.org.uk/drug/botulinum-toxin-type-a.html (accessed 6 April 2018).
  6. Katsarava Z, Mania M, Lampl C et al. Poor medical care for people with migraine in Europe—evidence from the Eurolight study. J Headache Pain 2018; 19 (1): 10.
  7. All-Party Parliamentary Group on Primary Headache Disorders (APPGPHD). Headache disorders—not respected, not resourced: A report of the All-Party Parliamentary Group on Primary Headache Disorders (APPGPHD). APPGPHD, 2010. Available at: www.migrainetrust.org/wp-content/uploads/2015/12/2010Mar-APPGPHD_REPORT_Headache_Disorders-NotRespNotReso.pdf
  8. Scottish Intercollegiate Guidelines Network (SIGN). Pharmacological management of migraine. SIGN 155. SIGN, 2018. Available at: sign.ac.uk/sign-155-migraine.html
  9. Lipton R, Diamond S, Reed M et al. Migraine diagnosis and treatment: results from the American Migraine Study II. Headache 2011; 41 (7): 638–645.
  10. Lampl C, Rudolph M, Deligianni C, Mitsikostas D. Neck pain in episodic migraine: premonitory symptom or part of the attack? J Headache Pain  2015; 16: 80.
  11. Calhoun A, Ford S, Pruitt A, Fisher K. The point prevalence of dizziness or vertigo in migraine–and factors that influence presentation. Headache 2011; 51 (9): 1388–1392.
  12. General Medical Council. Good practice in prescribing and managing medicines and devices. GMC, 2013. Available at: www.gmc-uk.org/Prescribing_guidance.pdf_59055247.pdf
  13. British Association for the Study of Headache (BASH). Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type headache, cluster headache, and medication-overuse headache. 3rd edition (1st revision). Hull: BASH, 2010. Available at: www.bash.org.uk/wp-content/uploads/2012/07/10102-BASH-Guidelines-update-2_v5-1-indd.pdf
  14. Medicines and Healthcare products Regulatory Agency (MHRA). Medicines related to valproate: risk of abnormal pregnancy outcomes. MHRA, 2015. Available at: www.gov.uk/drug-safety-update/medicines-related-to-valproate-risk-of-abnormal-pregnancy-outcomes
  15. Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia 2018; 38 (1): 1–211.
  16. Kernick D, Stapley S, Hamilton W. GPs’ classification of headache: is primary headache underdiagnosed? Br J Gen Pract 2008; 58 (547): 102–104.