Meta-Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

Objective.- To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.- Non-steroidal anti-inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.- Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta-analysis if they were (1) double-blind, randomized, placebo-controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain-free, relief of migraine-associated symptoms, sustained headache relief, sustained pain-free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.- We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta-analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain-free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41-1.77, P < .00001), and 2.22 (95% CI 1.46-3.37, P = .0002), respectively, for headache relief at 2 hours and pain-free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine-associated symptoms, sustained headache relief, and sustained pain-free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04-1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.- The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain-free at 2 hours and improving migraine-associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head-to-head clinical trials.