Midazolam vs. Diphenhydramine for the Treatment of Metoclopramide-induced Akathisia: A Randomized Controlled Trial

Objectives To compare the effects of midazolam, which is a fast and short-acting benzodiazepine, and diphenhydramine, which is a widely used anticholinergic agent, in clinical practice for the treatment of metoclopramide-induced akathisia.
Methods All adults older than 17 years given metoclopramide for nausea and vomiting or for headache and who had akathisia were eligible for this clinical, randomized, double-blind trial. Patients were randomized to receive diphenhydramine or midazolam. Subjective, objective, and total akathisia scores and modified Ramsay Sedation Scale scores were recorded. Repeated-measures analysis of variance was used to compare the efficacy and side effects of the medications.
Results Forty-one (73.3%) of the 56 enrolled patients were women. The mean (±SD) age was 39.9 (±15.7) years in the diphenhydramine group and 40.9 (±16.2) years in the midazolam group. Mean subjective, objective, and total akathisia scores in the first 5 minutes declined considerably in the midazolam group compared with the diphenhydramine group (p < 0.001). However, the mean Ramsay Sedation Scale score in the first 15 minutes increased significantly in the midazolam group compared with the diphenhydramine group (p < 0.001).
Conclusions Midazolam can correct the symptoms of metoclopramide-induced akathisia faster than diphenhydramine, but it causes more sedation.