Which Parenteral Treatment Is Best for Acute Migraine?

Summary and Comment |
March 6, 2014

Which Parenteral Treatment Is Best for Acute Migraine?

  1. Amy R. Tso, MD

A randomized, double-blind, comparative-efficacy trial suggests that intravenous valproate is inferior to both metoclopramide and ketorolac for treatment of acute migraine.

  1. Amy R. Tso, MD

Treatment for acute migraine is a common reason for emergency department (ED) visits, where adequate therapy can prevent admission for symptom control. In this study, researchers randomized 330 patients presenting to a single ED with acute migraine to receive one of three parenteral therapies: valproate (1 g), metoclopramide (10 mg), or ketorolac (30 mg). Baseline pain severity on a verbal 0-to-10 scale was ≥7 in all enrolled patients. The primary outcome was improvement in pain severity 1 hour after treatment, with a between-group difference of 1.3 points representing a minimum clinically significant change. The authors performed an intention-to-treat analysis for each of the three pairwise comparisons.

Valproate recipients improved by 2.8 points, compared with 4.7 points for metoclopramide and 3.9 points for ketorolac. More valproate recipients required additional rescue medications (69%) compared with metoclopramide (33%) and ketorolac recipients (52%). Despite a 6% incidence of feeling “very restless” in the metoclopramide group (vs. 1% each in the valproate and ketorolac groups), a greater proportion of metoclopramide recipients would want to receive the same medication at a future ED visit for migraine compared with the other two groups (61%,vs. 26% valproate and 40% ketorolac).


Several small, open-label series have shown intravenous valproate to be an effective acute migraine therapy. In most of the small, randomized trials, valproate was similarly or more efficacious compared with other commonly used acute migraine treatments, including two trials with metoclopramide as part of the comparator group. This trial is by far the largest and showed valproate to be inferior to metoclopramide. Metoclopramide also trended toward being superior to ketorolac on most outcomes. Almost all patients enrolled in this study were not taking a migraine preventive, and the generalizability of these results to a more severe or refractory population is not known. Even with the use of additional rescue medications, few patients in all groups experienced sustained headache freedom for 24 hours (valproate 4%; metoclopramide 11%; ketorolac 16%), highlighting an unmet need in the acute treatment of severe migraine.

Dr. Tso is a Headache Fellow at the University of California, San Francisco, Headache Center.


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