Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews

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.

1

Sumatriptan versus placebo. Calculated NNTs for a pain‐free response after a specified time, in participants treating moderate or severe migraine pain. Results for the five most commonly used dose and route of administration combinations, listed in rank order. PF2: pain‐free at two hours; PF1: pain‐free at one hour; 24h SPF: 24‐hour sustained pain‐free. Oral doses are shown with blue bars, subcutaneous doses are shown with red bars, intranasal doses are shown with yellow bars, and rectal doses are shown with green bars.

2

Sumatriptan versus placebo. Calculated NNTs for headache relief after a specified time, in participants treating moderate or severe migraine pain. Results for the five most commonly used dose and route of administration combinations, listed in rank order. HR2 (headache relief at two hours); HR1 (headache relief at one hour); 24h SHR (24‐hour sustained headache relief). Oral doses are shown with blue bars, subcutaneous doses are shown with red bars, intranasal doses are shown with yellow bars, and rectal doses are shown with green bars.

3

Sumatriptan versus placebo. Calculated NNHs for any adverse event within 24 hours of dosing, in participants treating moderate or severe migraine pain. Results for four of the five most commonly used dose and route of administration combinations (adverse event information for rectal sumatriptan not available), listed in rank order. Oral doses are shown with blue bars, subcutaneous doses are shown with red bars, and intranasal doses are shown with yellow bars.

4

Placebo response rates for the primary efficacy outcomes, by route of administration. Response rates of each outcome are grouped by colour to facilitate comparison between different routes of administration. Proportion of placebo‐treated participants pain‐free at two hours are shown with blue bars, pain‐free at one hour with purple bars, 24‐h sustained pain‐free with green bars, headache relief at two hours with red bars, headache relief at one hour with yellow bars, and 24‐h sustained headache relief with a pink bar.

5

Sumatriptan versus placebo. Calculated NNTs for relief of migraine‐associated symptoms and functional disability after two hours, in participants treating moderate or severe migraine pain. Results for the five most commonly used dose and route of administration combinations, listed in rank order. Oral doses are shown with blue bars, subcutaneous doses are shown with red bars, intranasal doses are shown with yellow bars, and rectal doses are shown with green bars.