Background: Although there are many medications available to treat migraine, none is uniformly effective. Many patients do not receive adequate treatment; some patients experience no relief two hours after taking an oral migraine medication; and many patients experience recurrence within 24 hours of taking a medication. Researchers hypothesize that combination therapy may relieve symptoms more effectively than monotherapy. Two classes of therapy target different aspects of the migraine pathway. Nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans alter the early and latter stages of a migraine attack, respectively. In combination, these drugs may not only treat the acute attack but also prevent recurrence. Brandes and colleagues examined the effectiveness and safety of different migraine treatments.
The Study: The authors reviewed the results of two randomized, double-blind clinical trials. Both studies compared a fixed-dose tablet containing sumatriptan (85 mg) plus naproxen (500 mg) with placebo and with each medication alone for the acute treatment of migraine. Participants included men and nonpregnant, nonlactating women who were 18 to 65 years of age. Participants had at least a six-month history of migraine, with or without aura, and had an average of two to six moderate or severe migraine episodes monthly that they could distinguish from other types of headache. Patients were excluded if they had more than six migraine attacks monthly or were using migraine prophylactic medication containing ergotamine (Ergomar), monoamine oxidase inhibitors, St. John's wort, or NSAIDs. In the first study, 1,677 patients were randomly selected to receive sumatriptan/naproxen (Trexima; under approval by the U.S. Food and Drug Administration), sumatriptan (Imitrex) alone, naproxen (Naprosyn) alone, or placebo. In the second study, 1,736 patients were randomly selected to receive one of the same treatment options as in the first study. Patients recorded details about their migraines. Patients who were not able to treat a migraine during the study were excluded. Two hours after dosing, treatment effectiveness was assessed by measuring headache relief and the incidence of photophobia, phonophobia, and nausea. Twenty-four hours after treatment, the researchers also assessed whether patients remained pain free with no nausea or use of rescue medication. The incidence of adverse effects determined clinical safety.
Results: In both studies, sumatriptan/naproxen was significantly more effective than placebo two hours after dosing. Study 1 showed the incidence of pain relief was 65 percent with combination therapy, 55 percent with sumatriptan, 44 percent with naproxen, and 26 percent with placebo. Study 2 showed the incidence of pain relief was 57 percent with combination therapy, 50 percent with sumatriptan, 43 percent with naproxen, and 29 percent with placebo. At 24 hours, significantly more patients who received combination therapy had sustained pain relief than patients who received monotherapy or placebo. In study 1, the incidence of sustained pain-free response was 25 percent with combination therapy, 16 percent with sumatriptan, 10 percent with naproxen, and 8 percent with placebo. In study 2, the incidence of sustained pain-free response was 23 percent with combination therapy, 14 percent with sumatriptan, 10 percent with naproxen, and 7 percent with placebo. There was no statistically significant difference in safety between combination therapy and sumatriptan or naproxen therapy alone.
Conclusion: The authors conclude that a fixed-dose sumatriptan/naproxen tablet relieves acute migraine symptoms more effectively than monotherapy with sumatriptan or naproxen. Moreover, the combination therapy is well tolerated by patients.