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Therapeutics

Subcutaneous sumatriptan reduced pain and functional disability in migraine

ACP J Club. 1991 Nov-Dec;115:84. doi:10.7326/ACPJC-1991-115-3-084


Source Citation

The Subcutaneous Sumatriptan International Study Group. Treatment of migraine attacks with sumatriptan. N Engl J Med. 1991 Aug 1;325:316-21. [PubMed ID: 1647495]


Abstract

Objective

To determine the efficacy of sumatriptan in the treatment of migraine attacks.

Design

Randonized, double-blind, placebo-controlled trial.

Setting

58 hospital neurology clinics, pain clinics, and doctors' offices in 10 countries.

Patients

639 men and women (age range 18 to 65 y) with ≥ 1 year history of either classic or common migraine, as defined by the International Headache Society, with ≤ 6 attacks per month. Patients were excluded for history of major cardiac, vascular, hepatic, or renal disease; epilepsy; psychiatric illness; hypertension; use of drugs including opiates, tranquilizers, ergot-containing drugs (≥ 10 mg/wk), and alcohol (> 315 g/wk), or use of either ergot-containing preparations within 24 hours or analgesics within 6 hours after administration of the study drug.

Intervention

At the time of a moderate or severe headache, 639 patients were randomly allocated to receive a subcutaneous injection of 6 mg of sumatriptan (n = 423), 8 mg of sumatriptan (n = 106), or placebo (n = 110). Patients who were not completely free of pain after 60 minutes then received a second, double-blind injection: of placebo if they had initially received placebo or 8 mg of sumatriptan; or of either placebo or 6 mg of sumatriptan, assigned randomly, if they had initially received 6 mg of sumatriptan.

Main outcome measures

Decrease in severity of headache pain and level of functional disability, each rated on a 4-point scale.

Main results

At 60 minutes, about 25% of patients receiving placebo had mild or no pain; 47% more patients (95% CI 38% to 57%) receiving 6 mg and 54% more patients (CI 43% to 65%) receiving 8 mg of sumatriptan had little or no pain (P< 0.001 for both sumatriptan regimens vs placebo; no difference between 6 mg and 8 mg of sumatriptan). Patients' ability to function normally was greater 60 and 120 minutes after injection with sumatriptan compared with placebo (all comparisons P < 0.001). Second injections of active drug at 60 minutes did not improve initial responses. 44% of placebo patients, but only 8% to 12% of sumatriptan patients, required "rescue" medication at 120 minutes (all comparisons P< 0.001). Response to sumatriptan was similar among patients with and without auras before their headache and among patients treated early (≤ 4 hours after onset) or later. Transient mild side effects occurred in about one third of placebo patients and one half of sumatriptan patients.

Conclusion

Sumatriptan, 6 mg, administered subcutaneously was an effective treatment for migraine.

Source of funding: None stated.

Address for article reprint: Dr. M.D. Ferrari, Department of Neurology,University Hospital, P.O. Box 9600, 2300R C Leiden, the Netherlands.


Commentary

Medications such as ergotamine and isometheptene are commonly used to abort migraine headaches. Unfortunately, for greatest efficacy, these medications need to be given as early as possible in the course of the headache, before the pain is well established. Side effects such as nausea frequently limit the use of the standard abortive medications.

In this well-designed study, the Subcutaneous Sumatriptan International Study Group showed that a 6-mg subcutaneous dose of sumatriptan causes a dramatic improvement in migraine headache pain. The results were clinically as well as statistically significant. This therapeutic effect occurs even if the treatment is delayed for > 4 hours after the onset of the headache. No major side effects were reported from the 6-mg dose of sumatriptan. The other major advantage of sumatriptan is that it can be given subcutaneously, which circumvents the problem of poor oral absorption of ergotamine during migraine headaches. The subcutaneous route is also useful in migraine headaches associated with nausea.

Clinicians should strongly consider using subcutaneous sumatriptan as abortive treatment for severe migraine headaches.

Barbara Scherokman, MD
Uniformed Services University of the Health SciencesBethesda, Maryland, USA