Abstract

Background

Migraine is a highly disabling condition for the individual and also has wide‐reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. It is available for administration by four different routes: oral, subcutaneous, intranasal, and rectal.

Objectives

To summarise evidence from four Cochrane intervention reviews on the efficacy and tolerability of sumatriptan in the treatment of acute migraine attacks in adults by four routes of administration (oral, subcutaneous, intranasal, and rectal) compared with both placebo and active comparators.

Methods

The included reviews were written by the authors of this overview; no additional searching was carried out. All included reviews were conducted according to a standard protocol and reported a standard set of outcomes. From each individual review we extracted results for pain relief at different levels, and adverse events. No additional statistical comparison was undertaken as part of the overview. We focused on the most important findings for doses and routes licensed in North America or Europe (oral 25 mg, 50 mg, 100 mg; subcutaneous 4 mg, 6 mg; intranasal 5 mg, 10 mg, 20 mg; rectal 25 mg).

Main results

Included reviews provided data for 18 different dose and route of administration combinations in 52,236 participants. Data for the primary outcomes sought were generally well reported, and involved adequate numbers of participants to give confidence in the results, except for the rectal route of administration, where numbers were low.

Subcutaneous administration was the most effective, with pain reduced from moderate or severe to none by two hours in almost 6 in 10 people (59%) taking 6 mg sumatriptan, compared with approximately 1 in 7 (15%) taking placebo; the number needed to treat (NNT) was 2.3 (95% confidence interval 2.1 to 2.4) with 2522 participants in the analysis. The most commonly used doses of oral, rectal, and intranasal sumatriptan also provided clinically useful pain relief, with the oral 50 mg dose providing complete relief of pain in almost 3 in 10 people (28%) compared with about 1 in 10 (11%) after placebo (NNT 6.1 (5.5 to 6.9) in 6447 participants). Subcutaneous administration provided more rapid pain relief than the other routes. Taking medication early, when pain was mild, was more effective than waiting until the pain was moderate or severe.

The most effective dose of sumatriptan for each route of administration for the outcome of headache relief (pain reduced from moderate or severe to none or mild) at two hours was oral 100 mg (NNT 3.5 (3.2 to 3.7) in 7811 participants), subcutaneous 6 mg (NNT 2.1 (2.0 to 2.2) in 2738 participants), intranasal 20 mg (NNT 3.5 (3.1 to 4.1) in 2020 participants), and rectal 25 mg (NNT 2.4 (1.9 to 3.4) in 240 participants).

Adverse events were generally of mild or moderate severity, of short duration, and more common with subcutaneously administered sumatriptan and higher doses of oral and intranasal sumatriptan than with other dose and route combinations.

Authors' conclusions

Sumatriptan is an effective abortive treatment for acute migraine attacks, but is associated with increased adverse events relative to placebo. The route of administration influences efficacy, particularly within the first hour after administration. Subcutaneous sumatriptan shows the greatest efficacy in terms of pain relief, but at the expense of relatively high levels of adverse events, and with a high financial cost compared with other routes. Information about the relative efficacy of the different routes of administration for different outcomes should help to inform decisions about the suitability of sumatriptan as a migraine treatment, as well as about the most appropriate way to administer the treatment for individual patients.

Author(s)

Christopher J Derry, Sheena Derry, R Andrew Moore

Abstract

Plain language summary

Sumatriptan (all routes of administration) for acute migraine attacks in adults

Migraine is a complex condition with a wide variety of symptoms. For many people, the main feature is a painful, and often disabling, headache. Other symptoms include disturbed vision; sensitivity to light, sound, and smells; feeling sick; and vomiting. Migraine affects about 1 person in 8, mainly women, and mainly in the age range of 30 to 50 years.

Sumatriptan is one of the triptan family of drugs used to treat migraine attacks. It can be given by four different routes: by mouth (oral), by injection under the skin (subcutaneous), by nasal spray (intranasal), and by suppositories (rectal). Separate Cochrane reviews for each of these routes provided information on how well sumatriptan worked at reducing headache pain in over 50,000 people with migraine. For oral, subcutaneous, and intranasal sumatriptan there was a large amount of information from good quality trials, but there was relatively little information about rectal administration.

This overview found that a single dose administered via any of these routes was effective in relieving migraine headache pain.

The subcutaneous route provided the best pain relief, with pain reduced from moderate or severe to none by two hours in almost 6 in 10 people (59%) taking the 6 mg dose, compared with approximately 1 in 7 (15%) taking placebo. The most commonly used doses of oral, rectal, and intranasal sumatriptan also provided useful pain relief. The oral 50 mg dose (the least effective of the commonly used dose and route combinations) provided complete relief of pain in almost 3 in 10 people (28%) compared with about 1 in 10 (11%) after placebo. Subcutaneous sumatriptan was also the fastest acting, providing more people with pain relief within one hour of treatment than any other route of administration.

Adverse events, which were mostly of mild or moderate severity and of short duration, were more common with subcutaneously administered sumatriptan and higher doses of oral and intranasal sumatriptan than with other dose and route combinations.

Author(s)

Christopher J Derry, Sheena Derry, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

Sumatriptan is an effective treatment for acute migraine in adults. Subcutaneous administration provides clinically useful outcomes for more individuals, and more rapidly, than other routes, but with increased adverse events. Other routes can provide largely the same outcomes for a smaller number of individuals, and with a slower onset of action. In practice, choosing the most appropriate route of administration of sumatriptan for the treatment of acute migraine involves balancing the strengths and weaknesses of each of the treatments discussed here, along with other practical considerations outside the scope of this review. These include questions of availability, patient preference, convenience of use, and cost. In the UK, a single dose of subcutaneous sumatriptan (6 mg) costs three to four times that of a single dose of oral (50 mg or 100 mg, branded) or intranasal formulations (20 mg), and over 60 times that of a single oral dose of a generic equivalent (data from BNF 2013). In the absence of other deciding factors, it seems likely that oral sumatriptan 50 mg will remain a starting point for triptan therapy, although it is imperative to recognise that for a substantial number of patients different doses, drugs, or routes of administration will be needed to ensure satisfactory results.

Generally, for the oral route of administration, commonly used doses of sumatriptan and other active comparators have equivalent efficacy for most outcomes, with higher doses being marginally better than lower doses. Eletriptan was the only comparator that consistently outperformed sumatriptan. It is likely that for oral administration, sumatriptan will remain a first‐line triptan therapy, with alternatives tried in the event of intolerance or inadequate response. Patients should be encouraged to treat their migraine attacks earlier, rather than wait until pain has become more severe, in order to have the best chance of successful treatment.

Implications for research 

The quantity of information available on sumatriptan is good, with the exception of rectal treatment and long‐term (24 hour) outcomes for all routes of administration. No given dose and route of administration provides adequate results in all individuals. Future trials should investigate whether, in the case of treatment failure, increasing the dose, or switching formulation or drug can increase the proportion who benefit, and benefit consistently.

Another useful line of research would be to investigate whether sumatriptan is a useful second‐line treatment for individuals who fail to get an adequate response with analgesics such as aspirin, ibuprofen, or paracetamol. Fixed‐dose combinations of sumatriptan and analgesics might also be more extensively explored, as combinations of drugs with different modes of action provide better pain relief in acute pain and migraine (Law 2013; Moore 2012).

Oral sumatriptan has become a standard against which a large number of newer migraine treatments are now tested, and hence a pool of information involving commonly used doses of oral sumatriptan is now available. However, there are still very few data comparing sumatriptan delivered via alternative routes with other active migraine treatments. It may be possible to derive some of the information needed to compare different treatments and routes of administration from network meta‐analysis of the data in these four reviews, which would reduce the need for new trials.

More complete and more consistent reporting of adverse events is necessary to properly assess their impact and make comparisons between different treatments.

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