July 7, 2008 — Early intervention with combination migraine therapy taken within an hour of headache onset effectively provides pain relief and also treats traditional and nontraditional migraine symptoms, new research suggests.
Two randomized double-blind placebo-controlled trials show that a single-tablet formulation of sumatriptan 85 mg and naproxen sodium 500 mg achieved 2-hour pain freedom in more than 50% of patients with acute migraine vs about 16% of those taking placebo.
"Unfortunately, many migraine sufferers put off treatment. This study provides more evidence that treating a migraine at the first sign of pain increases the likelihood of relief," study author Stephen Silberstein, MD, from Thomas Jefferson University, in Philadelphia, Pennsylvania, said in a statement from the American Academy of Neurology.
The paper, which reports the results of the 2 studies, is published in the July 8 issue of Neurology.
Multiple Mechanisms
According to the authors, evidence shows that early migraine intervention improves outcomes. Triptans effectively block pain transmission from the trigeminal nerve to the brainstem. However, the researchers note that the inflammation that accompanies migraine is not addressed by triptans.
Research indicates that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in migraine, likely because of their ability to address inflammation. The investigators speculate that NSAIDs are also beneficial in treating migraine with allodynia by suppressing central sensitization.
"The combination of a triptan with an NSAID addresses the multiple mechanisms of migraine, which have resulted in improved efficacy and superiority, compared with sumatriptan or naproxen alone," they write.
The 2 studies consisted of 576 and 535 migraineurs, respectively. At 2 hours, 52% and 51%, respectively, of sumatriptan/naproxen-treated patients were pain free, compared with 17% and 15% of their placebo-treated counterparts.
"Significant pain-free responses in favor of sumatriptan/naproxen were demonstrated as early as 30 minutes, maintained at 1 hour, and sustained from 2 to 24 hours," the authors write.
In addition, they report that the active-treatment groups experienced significantly lower rates of traditional migraine-associated symptoms, including phonophobia, nausea, and photophobia, than those taking placebo.
Those taking active treatment also had lower rates of nontraditional migraine symptoms, including neck pain/discomfort and sinus pain and pressure, than placebo-treated subjects.
Lower Rates of Rescue Medication
A total of 1111 subjects from 53 centers in the United States participated in the 2 identically designed studies. Men and women aged 18 to 65 years who had experienced 2 to 6 migraine attacks in the 3 months before the start of the trial were eligible to participate.
Patients treated a single migraine within 1 hour of the onset of migraine pain, while the pain was still mild, with either the sumatriptan/naproxen combination or placebo. Primary outcome was pain freedom 2 hours postdose.
Patients rated pain severity at the onset of pain, immediately before dosing, at 30 minutes, and at 1, 2, and 4 hours after dosing. They also recorded the presence or absence of neck pain/discomfort, sinus symptoms, and migraine-associated symptoms, including phonophobia, photophobia, and nausea, immediately before and 2 and 4 hours after dosing.
Adverse events (AEs), defined as any untoward medical occurrences experienced at any time after taking the study medication, regardless of suspected causes, were assessed. Investigators then assessed the possible relation between reported AEs and the study medication.
In addition to superior 2-hour pain-free responses at all study time points, significantly fewer patients treated with sumatriptan/naproxen used rescue medication within 24 hours than those treated with placebo — approximately 20% for active treatment and 47% for placebo
The authors report that AEs associated with sumatriptan/naproxen were generally mild and transient — with an overall incidence of 11% for the active-treatment group and 7% for placebo group. The most common were AEs were nausea and dizziness. No serious AEs or deaths were reported.
"These replicate studies demonstrate that the fixed-dose single-tablet formulation of sumatriptan/naproxen is an effective and well-tolerated therapy when administered during mild migraine pain, within 1 hour of onset. Physicians and patients should consider using both multimechanistic therapy and early intervention as an effective strategy for achieving the best clinical outcomes," the authors write.
The study was sponsored by Pozen and supported by GlaxoSmithKline. Dr. Silberstein's disclosures, which include research support from GlaxoSmithKline, can be viewed in detail in the original paper, as can those of the other investigators.
Neurology. 2008;70:114-121.
Medscape Medical News © 2008 Medscape
Cite this: Caroline Cassels. Early Treatment of Migraine With Combination Therapy Effective, Well Tolerated - Medscape - Jul 07, 2008.
Comments