• Benjamin W Friedman, Leonid Garber, Andrew Yoon, Clemencia Solorzano, Andrew Wollowitz, David Esses, Polly E Bijur, and E John Gallagher.
• From the Department of Emergency Medicine (B.W.F., A.Y., A.W., D.E., P.E.B., E.J.G.) and Pharmacy Department (C.S.), Montefiore Medical Center, and Medical College (L.G.), Albert Einstein College of Medicine, Bronx, NY.
• Neurology. 2014 Mar 18;82(11):976-83.

ObjectiveWe compared the efficacy of IV valproate with metoclopramide and with ketorolac in patients presenting to an emergency department (ED) with acute migraine.MethodsThis was a double-blind comparative efficacy trial. Patients were randomized to 1,000 mg sodium valproate, 10 mg metoclopramide, or 30 mg ketorolac, each administered as an IV drip over 15 minutes. The primary outcome was improvement in headache by 1 hour, measured on a verbal 0 to 10 scale, at baseline and 60 minutes later. Important secondary outcomes included (1) need for rescue medication in the ED, and (2) sustained headache freedom.ResultsThree hundred thirty patients were enrolled over 30 months beginning in October 2010. Baseline characteristics were comparable among the 3 arms. On the primary outcome, patients receiving IV valproate improved by a mean of 2.8 (95% confidence interval [CI]: 2.3, 3.3) on the 0 to 10 scale; those receiving IV metoclopramide improved by 4.7 (95% CI: 4.2, 5.2); and those receiving IV ketorolac improved by 3.9 (95% CI: 3.3, 4.5). On the secondary endpoints, 69% (95% CI: 60%, 78%) of patients receiving valproate required rescue medication, compared with 33% (95% CI: 24%, 42%) of metoclopramide patients and 52% (95% CI: 42%, 63%) of those assigned to ketorolac. Sustained headache freedom was achieved in 4% (95% CI: 0%, 7%) of those randomized to valproate, 11% (95% CI: 5%, 17%) of metoclopramide patients, and 16% (95% CI: 9%, 23%) receiving ketorolac. In the metoclopramide arm, 6% (95% CI: 3%, 12%) of patients reported feeling "very restless" after investigational medication administration.ConclusionsValproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide demonstrated superiority to ketorolac on several endpoints.Classification Of EvidenceThis study provides Class I evidence that in ED patients with acute migraine, IV valproate is inferior to metoclopramide or ketorolac in improving headache outcomes.

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