Despite guidelines recommending against opioids as first-line treatment for acute migraine, meperidine is the agent used most commonly in North American emergency departments. Clinical trials performed to date have been small and have not arrived at consistent conclusions about the efficacy of meperidine. We performed a systematic review and meta-analysis to determine the relative efficacy and adverse effect profile of opioids compared with nonopioid active comparators for the treatment of acute migraine.

We searched multiple sources (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and LILACS, emergency and headache medicine conference proceedings) for randomized controlled trials comparing parenteral opioid and nonopioid active comparators for the treatment of acute migraine headache. Our primary outcome was relief of headache. If this was unavailable, we accepted rescue medication use or we transformed visual analog scale change scores by using an established procedure. We grouped studies by comparator: a regimen containing dihydroergotamine, antiemetic alone, or ketorolac. For each study, we calculated an odds ratio (OR) of headache relief and then assessed clinical and statistical heterogeneity for the group of studies. We then pooled the ORs of headache relief with a random-effects model.

From 899 citations, 19 clinical trials were identified, of which 11 were appropriate and had available data. Four trials involving 254 patients compared meperidine to dihydroergotamine, 4 trials involving 248 patients compared meperidine to an antiemetic, and 3 trials involving 123 patients compared meperidine to ketorolac. Meperidine was less effective than dihydroergotamine at providing headache relief (OR=0.30; 95% confidence interval [CI] 0.09 to 0.97) and trended toward less efficacy than the antiemetics (OR=0.46; 95% CI 0.19 to 1.11); however, the efficacy of meperidine was similar to that of ketorolac (OR=1.75; 95% CI 0.84 to 3.61). Compared to dihydroergotamine, meperidine caused more sedation (OR=3.52; 95% CI 0.87 to 14.19) and dizziness (OR=8.67; 95% CI 2.66 to 28.23). Compared to the antiemetics, meperidine caused less akathisia (OR=0.10; 95% CI 0.02 to 0.57). Meperidine and ketorolac use resulted in similar rates of gastrointestinal adverse effects (OR=1.27; 95% CI 0.31 to 5.15) and sedation (OR=1.70; 95% CI 0.23 to 12.72).

Clinicians should consider alternatives to meperidine when treating acute migraine with injectable agents.