Dr Paul Ballinger explains how the SIGN guideline on headache can help GPs to diagnose migraine, and provide acute and preventive treatment for it
- Headache can be managed in primary care
- Episodic headache is usually migraine
- Aspirin and ibuprofen are suggested as first-line treatments for migraine
- Almotriptan, eletriptan, and rizatriptan are the preferred oral triptans for treatments of acute migraine
- Effective prophylaxis can reduce the frequency and severity of headaches
- Prophylactic agents should be trialled for a minimum period of 8 weeks
- Codeine-based analgesia and triptans are the agents most likely to induce medication overuse headache
Headaches are common and account for 4.4% of consultations in primary care.1 Undifferentiated headache (all headache types) has a 3-month prevalence of 70%,2 while migraine has a 1-year prevalence of 8% in men and 18% in women.3 Migraine has the highest prevalence in individuals between the ages of 20 and 60 years, reaching 25% among 40-year-old females.4
Ideally, headache should be managed in primary care: sheer patient numbers would overwhelm neurological services if the majority of individuals were referred; and a ‘trial and error’ approach, often required in headache management, lends itself to primary care work patterns. However, there is evidence to suggest that headache is often undertreated and incorrectly diagnosed in primary care.5 There is therefore a need for workable guidelines that GPs can readily apply. It is an unenviable task to write guidelines for headache, not least because headache medicine is hard to standardise and categorise. In other specialties a ‘one size fits all’ approach facilitates the production of guidelines, but patients with headache are unique in their variable and idiosyncratic response to treatment. Despite these obstacles, the SIGN guideline on the management of headache goes a long way towards empowering GPs to manage this condition effectively. The diagnosis and management of migraine, which is the main focus of this article, is the biggest headache challenge in primary care and it is instructive to review this condition with reference to the SIGN guideline.6
Episodic headache when encountered in primary care is usually migraine. The cardinal features include:6
- headache of moderate to severe intensity
- unilateral location
- light sensitivity
- sensitivity to noise
- exacerbation by physical activity.
In most cases only some of these features will be present and migraine is often undiagnosed. For example, a bilateral non-pulsatile headache, with slight photophobia and no nausea, and which is exacerbated by movement will still be migraine.6 The pain of migraine can be occipital, frontal, or even facial.
Autonomic symptoms including nasal congestion, conjunctival injection, and watering of the eyes can also occur during a migraine attack. A common pitfall is the misdiagnosis of a migraine variant characterised by facial pain and nasal congestion as a sinus headache.7 The International Headache Society has developed criteria for diagnosing migraine (see Table 1), but these are generally applied flexibly. If a patient misses one element of this definition, they are said to have probable migraine and usually still respond to migraine treatments.8
The SIGN guideline provides a useful pragmatic approach to the acute treatment of a migraine attack (see Figure 1).6 Aspirin 900 mg or ibuprofen 400 mg are suggested as first-line treatments. Both of these are available over the counter, have a good evidence base, are relatively safe, and for a proportion of patients provide excellent abortive treatment.
Acute treatments should ideally have a rapid onset of action as this is more likely to abort an attack before it becomes established.6 The fastest acting formulation of ibuprofen is ibuprofen lysine, which is sold over the counter as ibuprofen migraine. Other non-steroidal agents can be used and the fast-acting formulation is usually chosen. Thus, naproxen sodium 550 mg (rather than naproxen) or diclofenac potassium 50 mg (rather than diclofenac sodium) should be specified.9
The SIGN guideline reminds healthcare professionals that diclofenac suppositories of 100 mg provide a useful alternative to the oral route in those patients with nausea and vomiting.6
If non-steroidal anti-inflammatory drugs (NSAIDs) and simple analgesia fail to provide effective relief of the acute attack, triptans should be used.6 A common question asked by GPs is: ‘Which triptan should I use?’ There is no unequivocal answer to this as the patient response is idiosyncratic; different individuals respond to a given triptan by varying degrees. However, a landmark meta-analysis showed that almotriptan 12.5 mg, eletriptan 40–80 mg and rizatriptan 10 mg had slightly better profiles as measured by 2-hour pain-free status and adverse event rates.10 It is noteworthy that the SIGN guideline recommends these medications as a first-line triptan choice in preference to cheaper generic sumatriptan.6 When cost is an issue, many primary care trust prescribing advisers would urge that generic sumatriptan (at about one-third of the price) should be used first line. Almotriptan is often considered to offer the best overall balance of good efficacy with few side-effects.11
A necessary principle when using triptans is a readiness to switch to a different triptan if the first is ineffective.6 A second choice of triptan will often work where the first has failed. For example, 80% of patients who do not respond to sumatriptan 100 mg will respond to rizatriptan 10 mg or zolmitriptan 5 mg.12 A pragmatic approach is to give patients a prescription for two different triptans and allow them to select their preferred choice after an empirical trial in which they alternate the triptan used to treat acute attacks.
The efficacy of a triptan may be potentiated by combining it with an NSAID, such as naproxen sodium 550 mg or diclofenac potassium 50 mg.13 Readers of the SIGN guideline may be puzzled as to why the sumatriptan/naproxen sodium combination is suggested as the preferred combination, when sumatriptan itself is not a first-line choice of triptan. The answer is that although in clinical practice all triptans may be combined with NSAIDs, only this combination has good evidence from clinical studies.14 This fixed combination is now marketed as a product in the US.
The principle of combining acute treatments of different classes is also employed with anti-emetics. In particular, the combination of aspirin 900 mg and metoclopramide 10 mg has better efficacy than either drug alone.6
A cardinal rule in treating acute migraine is to avoid the use of codeine-based drugs, such as co-codamol or co-proxamol, which leads to more frequent attacks and medication overuse headache (MOH). This is one of the commonest mistakes made in primary care and the SIGN guideline rightly flags up a warning.6
Many patients know intuitively that the earlier the headache attack is treated the greater the chance of success; there is also a wealth of supportive evidence.15,16 Why is this? The migraine process can be interrupted and reversed if treated before a critical point is reached. If however, the critical point at which sensitisation of key neurones involved in pain transmission has already occurred, then treatment may be ineffective. Too often a patient will wait to be sure that their headache really is a migraine before embarking on acute treatment, by which time it may be too late. Similarly when a patient wakes with a migraine it is often well established and unresponsive to acute treatment.15,16
Prophylaxis is an important element in the management of migraine and is generally underused. Effective prophylaxis will reduce the number of headache attacks by about 50% and often reduces their severity.17 However, it often fails because both doctor and patient have unrealistic expectations. Furthermore, a prophylactic should be trialled for at least 8 weeks before considering it a failure.18
Many GPs need clear guidance about when to start prevention. In situations in which the patient is using increasing quantities of triptans, usually more than 10 per month, it is important to introduce prophylaxis to prevent this escalating into MOH. The SIGN guideline states that prophylaxis should be used when migraine interferes with daily routine and when acute therapies are overused. A US guideline suggests frequent headaches as an additional indication but it fails to define the frequency.19 Thus, there is a good deal of individual discretion required when deciding to start prophylaxis and it would be helpful if the SIGN guideline was able to address this issue. Prophylaxis should also be started if a patient develops chronic migraine (defined as more than 15 days of headache a month).20
Preventive treatment not only reduces the number of attacks, but can also prevent progression of episodic migraine to chronic migraine.21
Choice of prophylactic agent
As with treatment of acute migraine attacks, every patient is different and there is no ‘right’ prophylactic agent. Many drugs have been shown to have prophylactic properties, but three classes dominate and are used first line:6
- Beta blockers: propranolol 80–240 mg daily
- amitriptyline 25–150 mg daily or
- venlafaxine 75–150 mg daily
- topiramate 50–200 mg daily or
- sodium valproate 800–1500 mg daily.
It is essential to allow a preventive treatment a period of 8 weeks in order to determine if it will be effective and to titrate slowly to a dose that provides good efficacy, but with minimal side-effects. The latter is as much an art as a science and sometimes very slight ‘tweaking’ of a dose will provide the right balance of these two factors. Some patients will obtain a therapeutic benefit at doses lower than those stated above. For example, a proportion of patients can only tolerate 15 mg of topiramate and further increases cause side-effects. In general, the dose of a prophylactic agent is increased at weekly intervals in the titration process.
The patient’s history will often guide the clinician in the selection of a first-line prophylactic agent. For example, a patient with a poor sleep pattern may be best served by amitriptyline, whereas if there is co-existing asthma, beta blockers will be contraindicated. Topiramate, which often causes some weight loss, has a particular advantage in patients who are obese, as all the other pharmacological options have the potential to cause weight gain.6 The SIGN guideline explains this in some detail. As with acute treatments, if the first choice is poorly tolerated or ineffective, then switching to a second agent is often worthwhile.
|Table 1: Migraine without aura diagnostic criteria|
|Reproduced with permission for International Headache Society. The international classification of headache disorders, 2nd edition. Cephalagia 2004; 24 (Suppl 1): 8–160|
|Figure 1: Suggested algorithm for acute treatment of migraine based on SIGN recommendations6|
Medication overuse headache
Diagnosis and indications
Medication overuse headache is defined as headache that is present for over 15 days per month, which has developed or worsened while taking symptomatic medication. Many patients with chronic migraine (defined as more than 15 days of migraine headache a month) have co-existing medication overuse and there is overlap between these two headache types. When migraine increases in attack frequency, the patient will use inevitably greater quantities of analgesia or triptans that in turn create a vicious cycle of even more frequent headaches and further triptan/analgesia overuse.
Codeine-based analgesia such as co-codamol or co-dydramol and triptans are the agents most likely to induce MOH whereas NSAIDs are relatively safe in this respect. In our practice we limit the number of triptans that can be prescribed on the repeat system to no more than 10 each month. When a patient does request larger quantities of triptans, they should be reviewed and preferably started on a prophylactic treatment. The character of the headache tends to change in chronic migraine with medication overuse. There is often a dull background pain that is relatively featureless with superimposed migrainous exacerbations. If the medication can be successfully withdrawn, then the patient often reverts to episodic migraine.6
The management of MOH is a gradual or abrupt withdrawal of the medication. There has been a debate among headache physicians about whether this manoeuvre should be coupled with starting a prophylactic agent. There is now an increasing trend towards starting topiramate at the same time as withdrawing the medication.6,22,23
The SIGN guideline includes sections on pregnancy and menstrual migraine.6 When menstrual migraine occurs with the combined contraceptive pill many GPs treat this with the simple expedient of advising that the pill be taken for an extended period of 9 weeks. This is not mentioned in the guideline presumably because the evidence base is weak.
Menstrual migraine can be effectively treated using ‘mini prophylaxis’. In this technique the patient is asked to take a triptan daily during the days when they would expect to experience the migraine, usually 2 days before the period, and for a duration of about 4 days. The longer-acting triptans are usually chosen:
- frovatriptan 2.5 mg once daily or
- naratriptan 1 mg twice daily.6
Migraine usually improves during pregnancy. Paracetamol 1000 mg can be used throughout pregnancy, but if this is ineffective then aspirin 300 mg or ibuprofen 400 mg can be used in the first and second trimester.6
Other headache types
Although I have discussed migraine for the purposes of this article, the SIGN guideline discusses other headache types including tension-type headache, cluster headache, secondary headache, and thunder clap headache. Ideally, these headaches should be referred to specialist care.
Further details on the characteristics and treatment of these types of headache are provided in the SIGN guideline. The guideline provides a much-needed resource to treat headache in primary care. If I had to give a bottom line message to GPs it would be this: use the section on acute migraine treatment in the Quick Reference Guide,24 and start prophylaxis if the frequency of headaches starts to increase and certainly before it reaches over 15 days per month.
- Headache is a common and usually benign condition, but often causes diagnostic uncertainty and neurological referral
- Migraine has specific diagnostic criteria and local guidelines or prompts for primary care staff could promote confidence in making this diagnosis
- The treatment of acute attacks of migraine and prophylaxis could be laid out in local prescribing guidelines as in this article
- Commissioners working with prescribing advisers should weigh up the efficacy of drugs against their costs in such guidance
- Commissioners could consider specific headache clinics in primary care or ‘clinical advice services’ in referral management centres to help reduce unnecessary consultant referrals
- Tariff cost (2009–2010):a
- general medicine outpatient = £189 (new), £91 (follow up)
- Latinovic R, Gulliford M, Ridsdale L. Headache and migraine in primary care: consultation, prescription, and referral rates in a large population. J Neurol Neurosurg Psychiatry 2006; 77 (3): 385–387.
- Boardman H, Thomas E, Croft P, Milson D. Epidemiology of headache in an English district. Cephalalgia 2003; 23 (2): 129–137.
- Steiner T, Scher A, Stewart W et al. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia 2003; 23 (7): 519–527.
- Stewart W, Lipton R, Celentano D, Reed M. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA 1992; 267 (1): 64–69.
- Tepper S, Dahlöf 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.
- Scottish Intercollegiate Guidelines Network. The diagnosis and management of headache in adults. A national clinical guideline. SIGN 107. Edinburgh: SIGN 2008. Available at: www.sign.ac.uk/guidelines/fulltext/107/index.html
- Eross E, Dodick D, Eross M. The Sinus, Allergy and Migraine Study (SAMS). Headache 2007; 47 (2): 213–224.
- Silberstein S, Loder E, Diamond S et al. Probable migraine in the United States: results of the American Migraine Prevalence and Prevention (AMPP) Study. Cephalalgia 2007; 27 (3): 220–229.
- McNeely W, Goa K. Diclofenac-potassium in migraine: a review. Drugs 1999; 57 (6): 991–1003.
- Ferrari M, Roon K, Lipton R et al. Oral triptans (serotonin, 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001; 358 (9294): 1668–1675.
- Ferrari M. Tripstar: A comprehensive patient-based approach to compare triptans. Headache 2002; 42 (Suppl 1): 18–25.
- Mathew N, Kailasam J, Gentry P et al. Treatment of nonresponders to oral sumatriptan with zolmitriptan and rizatriptan: A comparative open trial. Headache 2000; 40 (6): 464–465.
- Krymchantowski A, Jevoux C. Combining different classes of drugs for the acute treatment of migraine. Drug Development Research 2007; 68 (7): 419–423.
- Brandes J, Kudrow D, Stark S et al. Sumatriptan-naproxen for acute treatment of migraine. JAMA 2007; 297 (13): 1443–1454.
- Brandes J, Kudrow D, Cady R et al. Eletriptan in the early treatment of acute migraine: Influence of pain intensity and time of dosing. Cephalalgia 2005; 25 (9): 735–742.
- Freitag F, Finlayson G, Rapoport A et al. Effect of pain intensity and time to administration on responsiveness to almotriptan: results from AXERT® 12.5 mg Time Versus Intensity Migraine Study (AIMS). Headache 2007; 47 (4): 519–530.
- Brandes J, Saper J, Diamond M et al; MIGR-002 Study Group. Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004; 291 (8): 965–973.
- Silberstein S. Chapter 22: Preventive treatment for migraine. In: Lipton R, Bigal M, editors. Migraine and other headache disorders. London: Informa Healthcare, 2006.
- Ramadan N, Silberstein S, Freitag F et al. (US Headache Consortium). Evidence-based guidelines for migraine headache in the primary care setting: Pharmacological management for prevention of migraine. Toronto: AAN, 2000.
- Silberstein S. Transformed and chronic migraine. In: Goadsby P, Silberstein S, Dodick D, editors. Chronic daily headache for clinicians. London: BC Decker Inc, 2005: 21–56.
- Silberstein S, Winner P, Chmiel J. Migraine preventive medication reduces resource utilization. Headache 2003; 43 (3): 171–178.
- Diener H-C, Dodick D, Goadsby P et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia 2009; 29 (10): 1021–1027.
- Hagen K, Albretsen C, Vilming S et al. Management of medication overuse headache: 1-year randomized multicentre open-label trial. Cephalalgia 2009; 29 (2): 221–232.
- Scottish Intercollegiate Guidelines Network. The diagnosis and management of headache in adults. Quick Reference Guide. SIGN 107. Edinburgh: SIGN, 2008. Available at: www.sign.ac.uk/guidelines/fulltext/107/index.html G