Metoclopramide for acute migraine: A dose-finding randomized clinical trial

Study objective: Intravenous metoclopramide is effective as primary therapy for acute migraine, but the optimal dose of this medication is not yet known. The objective of this study is to compare the efficacy and safety of 3 different doses of intravenous metoclopramide for the treatment of acute migraine. Methods: This was a randomized, double-blind, dose-finding study conducted on patients who presented to our emergency department (ED) meeting International Classification of Headache Disorders criteria for migraine without aura. We randomized patients to 10, 20, or 40 mg of intravenous metoclopramide. We coadministered diphenhydramine to all patients to prevent extrapyramidal adverse effects. The primary outcome was improvement in pain on an 11-point numeric rating scale at 1 hour. Secondary outcomes included sustained pain freedom at 48 hours and adverse effects. Results: In this study, 356 patients were randomized. Baseline demographics and headache features were comparable among the groups. At 1 hour, those who received 10 mg of intravenous metoclopramide improved by a mean of 4.7 numeric rating scale points (95% confidence interval [CI] 4.2 to 5.2 points); those who received 20 mg improved by 4.9 points (95% CI 4.4 to 5.4 points), and those who received 40 mg improved by 5.3 points (95% CI 4.8 to 5.9 points). Rates of 48-hour sustained pain freedom in the 10-, 20-, and 40-mg groups were 16% (95% CI 10% to 24%), 20% (95% CI 14% to 28%), and 21% (95% CI 15% to 29%), respectively. The most commonly occurring adverse event was drowsiness, which impaired function in 17% (95% CI 13% to 21%) of the overall study population. Akathisia developed in 33 patients. Both drowsiness and akathisia were evenly distributed across the 3 arms of the study. One month later, no patient had developed tardive dyskinesia. Conclusion: Twenty milligrams or 40 mg of metoclopramide is no better for acute migraine than 10 mg of metoclopramide.