Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Sumatriptan provided pain relief and improved the time to pain relief and clinical disability in patients with migraine

ACP J Club. 1993 May-June;118:70. doi:10.7326/ACPJC-1993-118-3-070


Source Citation

Mathew NT, Dexter J, Couch J, et al. Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. Arch Neurol. 1992 Dec;49:1271-6.


Abstract

Objective

To determine the optimal dose of sumatriptan for acute treatment of migraine in healthy adults.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

10 neurology and headache clinics.

Patients

242 adults (mean age 38 y, age range 18 to 60 y, 87% women) with migraine (International Headache Society definition). Exclusion criteria were previous participation, recent participation in another trial, recent acute illness, history of angina, hepatic or renal impairment, uncontrolled hypertension, pregnancy, lactation, use of analgesic or ergot-containing medications in the previous 24 hours, or use of simple analgesics in the previous 6 hours.

Intervention

Each arm of the study evaluated a different dose of sumatriptan. 30 patients in each of 6 groups received sumatriptan, 1 mg, 2 mg, 3 mg, 4 mg, 6 mg, or 8 mg. 62 patients received placebo. Medication was given subcutaneously in the deltoid. Investigators used discretionary rescue medication, excluding ergot-containing drugs, beginning 1 hour after dosing.

Main outcome measures

Migraine symptoms (nausea, vomiting, photophobia), pain relief, clinical disability, and adverse drug effects were measured every 10 minutes for the first hour and then every 30 minutes for 3 hours.

Main results

Pain relief (no or mild pain) at 1 hour for treatment groups was 24% for placebo; 43% for 1 mg; 57% for 2 mg; 57% for 3 mg; 50% for 4 mg; 73% for 6 mg; and 80% for 8 mg (P for all groups compared with placebo < 0.04). Pain relief was faster in the 6-mg and 8-mg groups with a significant reduction at 20 minutes (P < 0.001). All treatment groups compared with placebo had greater decreases in clinical disability (P < 0.001) and needed less rescue medication with the benefit increasing with increasing dosage. The 6-mg and 8-mg doses relieved nausea (P < 0.05 for both); all groups but the 2-mg group had a reduction in photophobia (P < 0.05). Improvement in these 2 associated symptoms were not dose related. More adverse events occurred for the groups receiving 3-mg and higher doses { P < 0.05}* in a dose-response relation. The most common adverse effects were injection-site reactions and tingling.

Conclusions

For adults with migraine receiving sumatriptan, pain relief, time to pain relief, and clinical disability were improved. Both benefits and adverse effects increased as dosage increased.

Source of funding: Not stated.

For article reprint: Dr. N.T. Mathew, The Houston Headache Clinic, 1213 Hermann Drive, Houston, TX 77704, USA. FAX 713-526-6369.

* P value calculated from data in the article.


Commentary

Severe headache, including migraine, is the most common neurologic complaint encountered by clinicians. It affects 10% of adults. The study by Mathew and colleagues confirms that injections of sumatriptan to treat migraine headache are well tolerated and more effective than placebo. In addition, neurologists in Europe who have extensive experience with this medication believe that subcutaneous sumatriptan is more effective than ergotamine and other treatments (1). Oral sumatriptan may be similarly effective.

Is sumatriptan the panacea long sought by those afflicted with frequent and severe headaches? Although it is now justified to state that sumatriptan is helpful for selected patients, the answer to this question is clearly no. First, when the frequency of headaches exceeds 2 per month, daily preventive therapy is often necessary. Sumatriptan has not been evaluated for migraine prophylaxis in clinical trials. Second, sumatriptan causes vasoconstriction, the magnitude of which may be important in patients with underlying coronary artery disease (2). Third, patients with migraines frequently misuse analgesics, and they (and prescribing physicians) may overuse sumatriptan. Fourth, patients with migraines seen in referral centers may not resemble patients in office-based practice who have a variety of migraine and muscle-contraction ("tension") headache symptoms, which often respond idiosyncratically and inconsistently to medication. Fifth, the relative expense of sumatriptan makes a careful cost-benefit analysis important (1). Finally, although sumatriptan is currently the pharmacologic agent of choice for treatment of acute migraine, an unexamined question is whether exclusive reliance on "stabs and tabs" is the best or only way to manage this chronic disorder. The empathic physician finds that understanding, counseling, and encouraging behavior and lifestyle modification will more often make the frequent use of medications, including sumatriptan, redundant (3).

Matthew Menken, MD
Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey, USA


References

1. Sumatriptan, serotonin, migraine, and money. Lancet. 1992;339:151-2.

2. Ottervanger JP, Paalman HJ, Boxma GL, Stricker BH. Transmural myocardial infarction with sumatriptan. Lancet. 1993;341:861-2.

3. Lance JW. Treatment of migraine. Lancet. 1992;339:1207-9.