A randomized trial of intravenous ketorolac versus intravenous metoclopramide plus diphenhydramine for tension-type and all nonmigraine, noncluster recurrent headaches

Abstract

Study objective: We compare metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, with ketorolac 30 mg intravenously in adults with tension-type headache and all nonmigraine, noncluster recurrent headaches.

Methods: In this emergency department (ED)-based randomized, double-blind study, we enrolled adults with nonmigraine, noncluster recurrent headaches. Patients with tension-type headache were a subgroup of special interest. Our primary outcome was a comparison of the improvement in pain score between baseline and 1 hour later, assessed on a 0 to 10 verbal scale. We defined a between-group difference of 2.0 as the minimum clinically significant difference. Secondary endpoints included need for rescue medication in the ED, achieving headache freedom in the ED and sustaining it for 24 hours, and patient's desire to receive the same medication again.

Results: We included 120 patients in the analysis. The metoclopramide/diphenhydramine arm improved by a median of 5 (interquartile range 3, 7) scale units, whereas the ketorolac arm improved by a median of 3 (IQR 2, 6) (95% confidence interval [CI] for difference 0 to 3). Metoclopramide+diphenhydramine was superior to ketorolac for all 3 secondary outcomes: the number needed to treat for not requiring ED rescue medication was 3 (95% CI 2 to 6); for sustained headache freedom, 6 (95% CI 3 to 20); and for wish to receive the same medication again, 7 (95% CI 4 to 65). Tension-type headache subgroup results were similar.

Conclusion: For adults who presented to an ED with tension-type headache or with nonmigraine, noncluster recurrent headache, intravenous metoclopramide+diphenhydramine provided more headache relief than intravenous ketorolac.

Trial registration: ClinicalTrials.gov NCT01011673.

Conflict of interest statement

Conflicts of interest: None

Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1

Tension-type headache criteria. From the International Headache Society’s International Classification of Headache Disorders, 2nd edition. Tension-type headaches can be further subdivided into infrequent episodic, frequent episodic, or chronic

Figure 2

CONSORT flow diagram

Figure 3

Each line depicts the baseline and 1hr pain score for an individual. Data are sorted by baseline pain score and then 1hr pain score, so the one patient who worsened after receiving the metoclopramide combination (from 9 to 10) appears in the figure after all of the other patients with a baseline score of 9.

Figure 4

Boxplots demonstrating % improvement in 0– 10 pain score one hour after medication administration.