Sumatriptan in acute migraine

Clinical bottom line: Subcutaneous, oral and intranasal sumatriptan is effective in the acute treatment of migraine. For successful treatment of migraine at one hour (for subcutaneous) or two hours (oral and nasal routes), the NNTs were 2.0 (1.9 to2.1), 3.0 (2.8 to 3.4) and 3.1 (2.7 to 3.8) respectively. Subcutaneous administration provides faster relief, but is associated with significantly more adverse effects than oral administration.

Sumatriptan is used in the acute treatment of migrane attacks and subcutaneously for cluster headaches. It is primarily a 5-HT ₁ receptor agonist, but does not cross the blood-brain-barrier. It is therefore thought to act on the the 5-HT ₁ -like cranial blood vessels such as the large conducting arteries and vessels within the meningeal circulation. Sumatriptan has low bioavailability (14%) compared with second generation triptans (45% to 75%), and has relatively short-lasting biological effects.

In the UK, sumatriptan accounts for 42,000 oral prescriptions (at £32 million) and 65,000 subcutaneous prescriptions (at £4.5 million).

Systematic review

Tfelt-Hansen P. Efficacy and adverse events of subcutaneous, oral, and intranasal sumatriptan used for migraine treatment. A systematic review based on number needed to treat. Cephalalgia 1998 18:532-538.

Date review completed: April 1997
Number of trials included: 30
Number of patients: 3127 (6 mg subcutaneous), 2890 (100 mg oral), 1420 (20 mg nasal)
Control group: placebo
Main outcomes: decrease in head pain from moderate or severe to mild or none, at one hour (subcutaneous route) or two hours (other routes); number-needed-to-treat (NNT) for moderate-severe pain to become mild-none (with 95% confidence intervals); therapeutic gain (with 95% confidence intervals); number-needed-to-harm (with 95% confidence intervals).

Inclusion criteria were randomised double-blind placebo-controlled trials of subcutaneous, oral and intranasal sumatriptan in the treatment of migraine attacks.

The number-needed-to-treat with 95% confidence intervals was calculated for each trial using a fixed effects model, and then for the pooled data. Therapeutic gain was calculated by subtracting the proportion of patients responding to placebo from the proportion of patients responding to sumatriptan. The number-needed-to-harm with 95% confidence interval was calculated using the original reporting of adverse events in the trials.

Findings

Subcutaneous sumatriptan

Twelve trials were included in the analysis. For 6 mg of subcutaneous sumatriptan, the number-needed-to-treat for success after one hour was 2.0 (1.9 to 2.1). The therapeutic gain was 51% (48% to 53%).

Oral sumatriptan

Twelve trials were included in the analysis. For 100 mg of oral sumatriptan, the number-needed-to-treat for success after two hours was 3.0 (2.8 to 3.4). The therapeutic gain was 33% (29.5% to 36%).

Nasal sumatriptan

Six trials were included in the analysis. For 20 mg nasal sumatriptan, the number-needed-to-treat for success after two hours was 3.1 (2.7 to 3.8). The therapeutic gain was 32% (27% to 38%).

Figure: Sumatriptan in the treatment of acute migraine for successful treatment (moderate/severe to mild/no pain) at one hour for subcutaneous sumatriptan and at two hours for oral and intranasal sumatriptan

In all trials with all routes of administration sumatriptan was statistically superior to placebo. Over a two hour period, the therapeutic gain for subcutaneous sumatriptan was consistently higher, although this difference lost significance at two hours. Subcutaneous sumatriptan had a faster onset of action than oral and nasal routes, with a modest (8%) therapeutic gain at 15 minutes. Oral and nasal sumatriptan took 30 minutes to reach a similar therapeutic gain.

Adverse effects

Numbers-needed-to-harm were calculated for subcutaneous and oral routes. With 6 mg subcutaneous sumatriptan, the number-needed-to-harm was 3.0 (2.7 to 3.4) based on 2183 patients. The number-needed-to-harm for 100 mg of oral sumatriptan was 8.3 (6.3 to 12.2).

Further references

The following references are covered by the current review:

Tfelt-Hansen P. Sumatriptan for the treatment of migraine attacks-a review of controlled clinical studies. Cephalalgia 1993; 13:238-44.

Harrison D. L, Slack M. K. Meta-analytic review of the effect of subcutaneous sumatriptan in migraine headache. Journal of Pharmacy Technology. 1996; 12(3): 109-114. ISSN: 8755-1225.

The following reference is a drug review: