Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache

Abstract

Objective: To determine whether IV metoclopramide 20 mg + diphenhydramine 25 mg (M + D) was more efficacious than IV placebo for acute moderate or severe posttraumatic headache in the emergency room.

Methods: We conducted this randomized, double-blind, placebo-controlled, parallel-group study in 2 urban emergency departments (EDs). Participants who experienced head trauma and presented to our EDs within 10 days with a headache fulfilling criteria for acute posttraumatic headache were included. We randomized participants in a 1:1 ratio to M + D or placebo. Participants, caregivers, and outcome assessors were blinded to assignment. The primary outcome was improvement in pain on a scale of 0 to 10 between baseline and 1 hour after 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. Patients receiving placebo reported mean improvement of 3.8 (SD 2.6), while those receiving M + D improved by 5.2 (SD 2.3), for a difference favoring metoclopramide of 1.4 (95% confidence interval [CI] 0.7-2.2, p < 0.01). Adverse events were reported by 35 of 81 (43%) patients who received metoclopramide and 22 of 79 (28%) of patients who received placebo (95% CI 1-30 for difference of 15%, p = 0.04).

Conclusion: M + D was more efficacious than placebo with regard to relief of posttraumatic headache in the ED.

Trial registration information: ClinicalTrials.gov Identifier: NCT03220958.

Classification of evidence: This study provides Class I evidence that for patients with acute moderate or severe posttraumatic headache, IV M + D significantly improved pain compared to placebo.

Figure 1. CONSORT Flow Diagram

CONSORT = Consolidated Standards for Reporting Trials.

Figure 2. Sport Concussion Assessment Tool PCSS Sums 1 Hour and 1 Week After Treatment

Twenty-two postconcussive symptoms were rated on a 7-item scale with 0 = none and 6 = severe. The sum is generated by adding the values obtained from all 22 items. Thus, the maximum possible score is 132. Patients who received metoclopramide + diphenhydramine reported fewer postconcussive symptoms 1 hour and 1 week after treatment. The figure depicts means with 95% confidence intervals. PCSS = Post Concussion Symptom Scale