The analgesic drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), and anti-emetic drugs suitable for the first-line treatment of migraine in the UK are listed in Table 1.

Prescribe a standard oral analgesic or ibuprofen for most people presenting with symptoms of migraine (these are also available over-the-counter), and advise the person to take the maximum licensed and tolerated dose as soon as symptoms become apparent (i.e. aura or premonitory symptoms).

Oral solutions are particularly suitable, especially if the person experiences difficulty swallowing or has experienced vomiting. Adult doses are:

Aspirin 600 mg to 900 mg every 4 hours, no more than four doses in 24 hours (not suitable for children).

Ibuprofen 400 mg to 600 mg every 4 hours, no more than four doses in 24 hours.

Paracetamol 1000 mg every 4 hours, no more than four doses in 24 hours. This is a less preferred option to be considered if other drugs are contraindicated.

Consider prescribing an alternative nonsteroidal anti-inflammatory drug (NSAID) if standard analgesia has been tried unsuccessfully (adults only):

Naproxen 750 mg to 825 mg as a single dose, followed by a further 250 mg to 275 mg up to twice in 24 hours (if necessary).

Diclofenac (potassium salt) 50 mg to 100 mg as a single dose, maximum 200 mg in 24 hours (if necessary).

Tolfenamic acid (rapid-release) 200 mg as a single dose, repeated once (if necessary).

If vomiting is preventing absorption, consider diclofenac suppositories 100 mg; two can be used in 24 hours.

Clarification / Additional information

For combination products containing analgesics and anti-emetics, see Choice of anti-emetic drug.

Basis for recommendation

These recommendations are based on Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007].

The drugs recommended are licensed for the treatment of acute migraine [BNF 55, 2008].

CKS recommends that oral paracetamol, aspirin, or ibuprofen are tried first in people with acute migraine.

There is most evidence from randomized controlled trials to support the effectiveness of simple analgesics and ibuprofen in the treatment of migraine, especially migraine with mild-to-moderate pain. These drugs are readily accessible and available over-the-counter.

Naproxen, diclofenac, and tolfenamic acid are prescription-only medicines. In general there is less evidence and experience to support their use.

Diclofenac suppositories are the only licensed non-oral NSAID formulation suitable for the treatment of migraine in primary care.

Prescribe anti-emetics if nausea or vomiting are prominent symptoms (domperidone and metoclopramide are also effective for pain relief when combined with analgesics). Consider:

Domperidone 10 mg to 20 mg, up to four doses in 24 hours (as tablets or suspension).

Metoclopramide 10 mg, up to three doses in 24 hours (as tablets or suspension, not recommended in children).

Prochlorperazine buccal tablets 3 mg to 6 mg, up to two doses in 24 hours.

Consider a combined analgesic and anti-emetic if this is more convenient than taking the components separately (although this is a more expensive option):

MigraMax^® — lysine acetylsalicylate (equivalent to aspirin 900 mg) and metoclopramide (10 mg) sachet. A further dose can be taken after 2 hours if necessary, up to three doses in 24 hours.

Paramax^® — paracetamol (500 mg) and metoclopramide (5 mg), tablets or sachets. Two doses should be taken at the onset of the attack, maximum six doses in 24 hours.

If vomiting is preventing oral absorption, consider domperidone suppositories 30 mg to 60 mg, maximum 120 mg in 24 hours.

Basis for recommendation

These recommendations are consistent with Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007].

The drugs recommended are licensed for the treatment of acute migraine [BNF 55, 2008].

Prokinetic anti-emetics are useful in treating migraine associated with nausea and vomiting. As well as their anti-emetic effect, they increase gastric emptying, and consequently increase the absorption of oral analgesics. Prochlorperazine is not a prokinetic drug, but is a phenothiazine with anti-emetic effects.

There is evidence from several randomized controlled trials (RCTs) that suggests that anti-emetics are an effective adjunct when combined with standard analgesics in the treatment of acute attacks.

From the available evidence, prochlorperazine and metoclopramide may reduce pain, whereas domperidone may shorten the duration of attacks, although it is difficult to interpret the effects of these drugs from RCTs.

Simple analgesics are generally considered to be safe when used for short periods of time at the appropriate dose.

Paracetamol should be avoided in people with liver disease, and some experts suggest that it should also be avoided in people who drink excessive quantities of alcohol.

Aspirin is not suitable in children younger than 16 years of age because of Reye's syndrome. It should be avoided in people with a history of peptic ulceration and used with caution in people with asthma or allergic diseases (because of bronchospasm).

The main contraindications to nonsteroidal anti-inflammatory drugs (NSAIDs) are known hypersensitivity, asthma, renal impairment, severe hepatic impairment, and a history of gastrointestinal bleeding or peptic ulceration.

For more information on cautions and contraindications, see the CKS topic on NSAIDs - prescribing issues.

There are limitations on using NSAIDs for migraine in pregnant and breastfeeding women; see Treatment in pregnancy or breastfeeding.

Anti-emetics are suitable for most adults:

Prochlorperazine is not recommended in children younger than 12 years of age.

Metoclopramide should be avoided in young people (20 years of age or younger), because extrapyramidal adverse effects are more common in this age group.

Domperidone should be avoided in:

Pregnant and breastfeeding women.

People taking medications that prolong the QT interval such as erythromycin and ketoconazole.

Be particularly cautious when prescribing domperidone to people aged over 60 years and people who have:

Existing prolongation of cardiac conduction intervals (particularly the QTc interval).

Electrolyte disturbance.

An underlying cardiac disease (such as congestive heart failure).

Basis for recommendation

Cautions and contraindications are based on information in the British National Formulary [BNF 55, 2008] and information regarding the cardiac risks of domperidone from the Medicines and Healthcare products Regulatory Agency (MHRA) in collaboration with McNeil Products Ltd., and Winthrop Pharmaceuticals [McNeil Products Ltd and Winthrop Pharmaceuticals UK Ltd, 2011]. The Summary of Product Characteristics for individual drugs can be obtained from the electronic Medicines Compendium (eMC) (www.medicines.org.uk).

Paracetamol and aspirin rarely have adverse effects when used for the short-term treatment of migraine:

Paracetamol has no notable adverse effects when used at the correct dosage.

Aspirin may cause gastrointestinal irritation, skin rashes, and bronchospasm. Use an alternative if these occur.

The risk of severe adverse effects (gastrointestinal or cardiovascular) from nonsteroidal anti-inflammatory drugs (NSAIDs) are lower in people younger than 65 years of age who are taking NSAIDs for short periods, which will include most people with migraine. In general, children tolerate ibuprofen better than adults do.

Ibuprofen may occasionally cause minor gastrointestinal adverse effects, such as discomfort, nausea, and diarrhoea. Other adverse effects, such as gastrointestinal bleeding, are less common but potentially serious.

Adverse effects associated with naproxen, diclofenac, tolfenamic acid, and mefenamic acid are likely to be more common and severe than with ibuprofen. For more information on managing the adverse effects of NSAIDs, see the CKS topic on NSAIDs - prescribing issues.

Anti-emetics are usually well tolerated in adults.

Prochlorperazine may cause sedation and extrapyramidal adverse effects (especially dystonia), but these are likely to be mild with occasional low-dose use.

Metoclopramide can induce acute dystonic reactions. However, these reactions are more common in younger people (particularly girls and young women) and people who are taking other drugs known to cause extrapyramidal effects. Other adverse effects include drowsiness, restlessness, and diarrhoea.

Domperidone is generally very well tolerated with few undesirable effects.

Extrapyramidal adverse effects are very rare as domperidone does not readily cross the blood-brain barrier.

Domperidone may be associated with an increased risk of ventricular tachyarrhythmias and sudden cardiac death: these risks may be higher in people aged over 60 years, and people who are taking more than 30 mg of domperidone daily.

Advise a person taking domperidone to seek prompt medical attention if symptoms such as syncope or tachyarrhythmias arise during treatment.

Basis for recommendation

Information on adverse effects are based on information in the British National Formulary [BNF 55, 2008] and information regarding the cardiac risks of domperidone from the Medicines and Healthcare products Regulatory Agency (MHRA) in collaboration with McNeil Products Ltd., and Winthrop Pharmaceuticals [McNeil Products Ltd and Winthrop Pharmaceuticals UK Ltd, 2011]. The Summary of Product Characteristics for individual drugs can be obtained from the electronic Medicines Compendium (eMC) (www.medicines.org.uk).

The triptans available in the UK are listed in Table 1.

Oral sumatriptan (50 mg or 100 mg) is recommended as the first-line triptan for most people. Zolmitriptan (2.5 mg), naratriptan (2.5 mg), rizatriptan (10 mg), eletriptan (40 mg), almotriptan (12.5 mg), and frovatriptan (2.5 mg) are more expensive alternatives, but it is difficult to predict any advantages of these drugs on the first occasion a triptan is used.

If vomiting restricts oral treatment, consider a non-oral formulation, such as zolmitriptan nasal spray (5 mg) or subcutaneous sumatriptan (6 mg).

Clarification / Additional information

For a full list of available triptan products, see Available products.

Basis for recommendation

These recommendations are consistent with Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007].

There is good evidence from several comparative meta-analyses and head-to-head trials on the effectiveness and tolerability of the triptans, which has led to the conclusion that there are clinical differences between the drugs, which may be important in some individuals [Ferrari et al, 2001; Gawel et al, 2001; Oldman et al, 2002]. However, CKS recommends sumatriptan to be used first in most people requiring a triptan because:

There is more evidence from randomized controlled trials to support the use of sumatriptan than any other triptan. Although the 100 mg dose has been most extensively studied and used as a comparator drug, it is reasonable to consider 50 mg as well, as the higher dose is only marginally more effective, and has more adverse effects [McCrory and Gray, 2003]. Although there is no evidence that any triptan is safer than another, sumatriptan is in the mid-range of tolerability compared with other triptans.

The clinical advantages seen with the other triptans will not be apparent until a response with sumatriptan has been observed first. For more information, see Treatment failure.

It is reasonable to prescribe a non-oral triptan on the first occasion if vomiting is known to be a problem with oral administration.

Subcutaneous sumatriptan (6 mg) is the most effective triptan regimen [Oldman et al, 2002], but is also the most expensive, and some people may be put off by the injection.

Intranasal sumatriptan (20 mg) is not recommended if there is vomiting, as it is absorbed through the oral route. Intranasal zolmitriptan (5 mg) may be a better option as about 30% of the drug is absorbed through the nasal mucosa [BASH, 2007].

If treatment with the initial choice of triptan (usually sumatriptan) proves to be inadequate, assess compliance, and consider:

Increasing to a dose of sumatriptan 100 mg (if not used already), or switching to a parenteral formulation (especially if vomiting is problematic). Subcutaneous sumatriptan 6 mg is the most effective triptan available.

Prescribing a more effective triptan, such as rizatriptan 10 mg, almotriptan 12.5 mg, eletriptan 40 mg, or eletriptan 80 mg (two 40 mg tablets).

If initial treatment was effective but poorly tolerated, check the correct dosage was used, and consider prescribing a better tolerated triptan:

Almotriptan is better tolerated and as effective as sumatriptan 100 mg.

Naratriptan and frovatriptan (both 2.5 mg) are better tolerated than sumatriptan 100 mg, but not as effective.

Lower doses of other triptans, such as rizatriptan (5 mg) and eletriptan (20 mg), are less likely to cause adverse effects, although this is an off-licence use of these drugs.

Clarification / Additional information

For information on what a person should do if they are experiencing relapses, see Advice to patients.

Basis for recommendation

These recommendations are based on Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007].

The triptans exhibit clinical differences which are important for some individuals for whom initial treatment has not been satisfactory (see Summary comparison).

There is evidence from a systematic review that rizatriptan, almotriptan, and eletriptan are more effective than sumatriptan 100 mg [Ferrari et al, 2002]. Sumatriptan 100 mg is marginally more effective than sumatriptan 50 mg [McCrory and Gray, 2003], whereas subcutaneous sumatriptan (6 mg) is the most effective available triptan [Oldman et al, 2002].

For new triptan users, tolerability is likely to be a bigger issue than lack of effectiveness [Cutrer et al, 2004]. There is evidence from a systematic review that almotriptan and naratriptan are better tolerated than sumatriptan 100 mg (but naratriptan is less effective) [Ferrari et al, 2002]. Frovatriptan is also probably better tolerated than sumatriptan, but it is considerably less effective [Poolsup et al, 2005].

Triptans should not be taken by:

People with uncontrolled hypertension.

People with, or at high risk of, cardiovascular disease. This is determined by the medical history and age of the person. If there is uncertainty, consider an exercise electrocardiogram, or referral to a cardiologist.

People with coronary vasospasm (including Prinzmetal's angina).

There are age restrictions on the use of triptans:

Children younger than 12 years of age should avoid taking triptans. Adolescents (12–18 years of age) may be prescribed sumatriptan nasal spray (10 mg).

Triptans are not licensed for people aged over 65 years, although if they have been previously used and found to be effective, there is no reason to stop prescribing them.

Triptans are contraindicated in pregnancy. Triptans are excreted in breast milk, so they should be avoided during breastfeeding, or milk should be discarded for 12–24 hours (see manufacturer's information).

A reduced dose of triptan is recommended for some triptans if there is hepatic or renal dysfunction:

Sumatriptan — do not exceed 50 mg in people with hepatic dysfunction.

Rizatriptan — prescribe 5 mg in people with hepatic dysfunction and moderate renal dysfunction, and in people receiving concomitant propranolol (avoid in severe renal dysfunction).

Eletriptan — prescribe 20 mg in people with renal dysfunction and avoid in severe hepatic dysfunction.

Rizatriptan — prescribe 5 mg in people with mild or moderate hepatic or renal dysfunction, or who are taking propranolol (leave at least 2 hours between doses of drugs).

Basis for recommendation

These recommendations are based on Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007], and the British National Formulary [BNF 55, 2008].

Triptans are not recommended in children or older people (over 65 years) because of a lack of evidence on their effectiveness and safety. However, CKS recommends that if an older person has previously found a triptan to be effective, the drug should be continued providing no cardiovascular comorbidity has developed in the meantime.

Post-marketing data from over 1000 women in the first trimester of pregnancy receiving sumatriptan indicated no increase in the risk of congenital defects. However, the manufacturer concluded this was insufficient to guarantee the drug's safety, and commented that data in the second and third trimesters were lacking [ABPI Medicines Compendium, 2008a].

The cardiovascular risk of triptans is probably very low in people without contraindications; although there have been isolated reports of myocardial infarction, these are usually related to unstable coronary heart syndromes such as Prinzmetal's angina, rather than atheroma.

Although adverse effects frequently occur with triptans, they are usually mild and self limiting, and many have also been recorded in people receiving inactive placebos. Common adverse effects (sometimes known as 'triptan sensations') include a warm-hot sensation, tightness, tingling, flushing, and feelings of heaviness or pressure in areas such as the face and limbs, and occasionally the chest:

Symptoms in the chest may mimic angina pectoris and cause considerable alarm. If the person is forewarned about these feelings, they rarely cause problems.

However, consider discontinuing the triptan if the person complains of intense chest pains or sensations, as this could be due to coronary vasoconstriction.

Other adverse effects are generally mild and self limiting for all triptans. They include nausea, dizziness, somnolence, dry mouth, and drowsiness. If drowsiness occurs, the person should be advised not to drive or perform other skilled tasks while affected.

Basis for recommendation

These recommendations are based on Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007] and the British National Formulary [BNF 55, 2008].

Triptans are regarded as relatively safe in the absence of contraindications. Evidence from a large number of randomized trials [Ferrari et al, 2002], and the large numbers of people exposed to sumatriptan, indicates that serious adverse effects are rare.

Although minor adverse effects are common and may affect drug compliance, this can be minimized by forewarning the person about the potential for altered sensations [Goadsby et al, 2002]. The large placebo response commonly observed in migraine trials suggest many of these symptoms occur as a result of the attack, rather than the treatment.

Triptans are contraindicated in people who are:

Taking monoamine oxidase inhibitors, or within 2 weeks of stopping a monoamine oxidase inhibitor.

Taking ergotamine or derivatives of ergotamine, including methysergide (both of which may be used by specialists as preventative treatments for cluster headache).

In addition, people taking eletriptan should not use CYP3A4 inhibitors (such as clarithromycin, erythromycin, ketoconazole, itraconazole, indinavir, nelfinavir, ritonavir). Other triptans are not metabolized by this route so are not expected to interact.

Triptans should be used with caution in people taking selective serotonin reuptake inhibitors (SSRIs), selective noradrenalin reuptake inhibitors (SNRIs), lithium, sibutramine, or St John's wort (because of the small but significant risk of serotonin syndrome).

If the person needs an antidepressant, consider using mirtazapine, trazodone, mianserin, or reboxetine in preference to an SSRI, SNRI or St John's wort.

Rizatriptan plasma levels are increased by propranolol. A maximum dose of rizatriptan 5 mg should be used. Alternatively, use another triptan.

Basis for recommendation

These recommendations are based on information from Stockley's drug interactions [Baxter, 2008] and the NICE guideline Depression in adults with a chronic physical health problem[NICE, 2009c].

Inform the person that mild symptoms (or 'triptan sensations') are common and not a cause for concern. However, if there are intense chest pains or sensations, the person should stop treatment and seek medical advice.

Advise the person to take the triptan as soon as pain develops (but not during aura, if present). After the first dose has been taken:

If the triptan successfully relieves pain, but there is relapse, a dose of triptan can be repeated within 2–4 hours.

Sumatriptan — three doses (total of 300 mg) of sumatriptan can be taken in 24 hours.

Almotriptan, eletriptan, naratriptan, and rizatriptan — two doses can be taken in 24 hours.

Zolmitriptan — four doses (total of 10 mg) can be taken in 24 hours.

If the triptan is ineffective, a further dose is unlikely to be effective and should not be taken. The exception to this is zolmitriptan (2.5 mg), where an additional 5 mg dose can be tried after 2 hours even if the first dose was unsuccessful.

Advise the person that it is important they are reassessed for more effective treatment if current triptan use continues to be inadequate.

Basis for recommendation

These recommendations are based on Guidelines for all healthcare professionals in the diagnosis and management of migraine, tension-type, cluster and medication-overuse headache, published by the British Association for the Study of Headache (BASH) [BASH, 2007], and the British National Formulary [BNF 55, 2008].

Chest pains:

Intense chest pains or sensations could be due to coronary vasoconstriction, so the person should be advised to discontinue treatment. For more details, see Adverse effects.

Timing of administration:

There is evidence that triptans should be taken immediately once pain has started, rather than delayed until pain is more severe. An open-label, randomized controlled trial (n = 112) found significant benefit with early rather than late treatment with sumatriptan 100 mg [Scholpp et al, 2004].

Relapse:

Relapse is a significant limitation of triptans, affecting 20–50% of triptan-treated migraine attacks. The recommendations are based on the product licences for the individual triptans.

If the person did not respond to an initial dose of triptan, they are unlikely to benefit from repeat administration.

Some experts recommend waiting for 2 pain-free days before a triptan is tried again.

However, data from the manufacturers of Zomig^® (zolmitriptan) suggest that a repeat dose of 5 mg may be beneficial, and this is reflected in the product licence [ABPI Medicines Compendium, 2008b].

Dosing regimen:

Propranolol — prescribe 80 mg modified-release propranolol (Inderal^® LA) initially. This can be increased to a maximum dose of 240 mg per day if necessary.

Metoprolol — prescribe 50 mg to 100 mg twice a day.

Timolol — prescribe 10 mg to 20 mg once a day.

Atenolol (unlicensed indication) — prescribe 25 mg to 100 mg once a day.

Contraindications and cautions:

Beta-blockers should be avoided in people with:

Asthma, or with chronic obstructive airways disease that has an asthmatic component, as they can precipitate bronchospasm that is unresponsive to beta₂-agonists.

Second-degree or third-degree heart block.

Beta-blockers should be used with caution in people with:

Unstable heart failure, as they can worsen the heart failure; this should be stabilized before initiation of a beta-blocker.

Peripheral vascular disease.

Diabetes, as they can slightly raise blood glucose levels and the response to hypoglycaemia may be delayed or symptoms of hypoglycaemia may not occur in the usual way. Avoid beta-blockers in people who experience frequent hypoglycaemia.

Adverse effects:

Adverse effects of beta-blockers include:

Cold extremities, paraesthesiae, and numbness.

Sleep disturbance or nightmares.

Fatigue, depression, and hypoglycaemia.

Sexual dysfunction.

[BASH, 2007; BNF 55, 2008]

For more information on the contraindications and adverse effects of beta-blockers, as well as information on drug interactions and monitoring, see the section on Beta-blockers in the CKS topic on Hypertension - not diabetic.

Before prescribing amitriptyline, explain to the person that the drug is being prescribed to reduce attacks of migraine, and not for depression.

Amitriptyline should be prescribed at a dose of 10 mg initially, and titrated upwards to a maximum dose of 150 mg, if required. Advise the person to take it 1–2 hours before bedtime (it has a sedative effect).

Amitriptyline should be avoided in people who have had a recent myocardial infarction or who have arrhythmia. It should be used with caution in people with ischaemic heart disease or epilepsy.

Common adverse effects include constipation, weight gain, dry mouth, sedation, nausea, and dizziness. These are usually apparent in the first couple of weeks of taking the drug and settle with continued use.

[BASH, 2007; BNF 55, 2008]