Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache.

OBJECTIVE To determine whether intravenous (IV) metoclopramide 20mg + diphenhydramine 25mg (M+D) was more efficacious than IV placebo for acute moderate or severe post-traumatic headache in the emergency room. METHODS We conducted this randomized, double blind, placebo controlled, parallel group study in two urban emergency departments (ED). Participants who experienced head trauma and presented to our EDs within 10 days with a headache fulfilling criteria for acute post-traumatic headache were included. We randomized participants in a 1:1 ratio to M+D or placebo. Participants, care givers, and outcome assessors were blinded to assignment. The primary outcome was improvement in pain on a 0-10 scale between baseline and one hour post treatment. RESULTS This study was completed between August 2017 and March 2020.We screened 414 patients for participation and randomized 160, 81 to M+D and 79 to placebo. Baseline characteristics were comparable between the groups. All enrolled participants provided primary outcome data. Placebo patients reported mean improvement of 3.8 (SD 2.6) while M+D improved by 5.2 (SD 2.3), for a difference favoring metoclopramide of 1.4 (95% CI 0.7, 2.2, p<0.01). Adverse events were reported by 35/81 (43%) of patients who received metoclopramide and 22/79 (28%) of patients who received placebo (95% CI for difference of 15%: 1, 30%, p=0.04). CONCLUSION Metoclopramide + diphenhydramine was more efficacious than placebo with regard to relief of post-traumatic headache in the ED. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that for patients with acute moderate or severe post-traumatic headache, IV metoclopramide + diphenhydramine significantly improved pain compared to placebo.