A Randomized Trial of Intravenous Ketorolac Versus Intravenous Metoclopramide Plus Diphenhydramine for Tension-Type and All Nonmigraine, Noncluster Recurrent Headaches

Abstract

Objective We compared metoclopramide 20 mg IV, combined with diphenhydramine 25 mg IV, to ketorolac 30 mg IV in adults with tension-type headache and all non-migraine, non-cluster recurrent headaches. Methods In this ED-based randomized, double-blind study, we enrolled adults with non-migraine, non-cluster 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 one 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: 1) need for rescue medication in the ED; 2) achieving headache freedom in the ED and sustaining it for 24 hours; and 3) 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 (IQR 3,7) scale units while the ketorolac arm improved by a median of 3 (IQR 2,6) (95%CI for difference: 0, 3). Metoclopramide + diphenhydramine were superior to ketorolac for all three secondary outcomes: the number needed to treat for not requiring ED rescue medication was 3 (95%CI: 2, 6), for sustained headache freedom 6 (95%CI: 3, 20), and for wish to receive the same medication again 7 (95%CI: 4, 65). Tension-type headache subgroup results were similar. Conclusions For adults who presented to an ED with tension-type headache or with non-migraine, non-cluster recurrent headache, IV metoclopramide + diphenhydramine provided more headache relief than IV ketorolac.

Comparison of parenteral treatments of acute primary headache in a large academic emergency department cohort

“…In prior studies, parenteral opiates were given to 25–60% of these patients 3,16,17 . Multiple expert reviews have reported that opiates should not be used as first-line therapy for migraine headaches in the ED or clinic 9,21–24 .…”

Efficacy measurement of ketorolac in reducing the severity of headache

“…Intravenous ketorolac was also compared with intravenous diphenhydramine plus metoclopramide for treatment of some primary headaches. The study concluded that for adults who presented to an ED with non-migraine, non-cluster primary headaches, intravenous diphenhydramine plus metoclopramide have better efficacy than intravenous ketorolac (27). Using a standard measuring tool like VAS and the precise selection of patients can be considered as the strengths in this study.…”

Metoclopramide and Diphenhydramine: A Randomized Controlled Trial of a Treatment for Headache in Pregnancy when Acetaminophen Alone Is Ineffective (MAD Headache Study)

“…IV metoclopramide has been shown to be effective in the treatment of acute migraines when compared with sumatriptan, 22,24 hydromorphone, 25 prochlorperazine, 23 and ketorolac. 26 Its use should be considered as early therapy in the treatment of acute migraines.…”