Use of Diphenhydramine for Pain Management in the Emergency Department: A Systematic Review and Meta-analysis

Abstract

BACKGROUND Diphenhydramine, commonly prescribed as an antihistamine drug, is not known for its analgesic effect and its use in acute pain management has not been thoroughly investigated. AIM In this study, we aim to explore the analgesic properties of diphenhydramine and its role in acute pain reduction in the emergency department (ED). METHODS A systematic review and meta-analysis were performed. The inclusion criteria were randomised controlled trials that investigated the effect of intravenous diphenhydramine on the management of acute pain. Acute pain reduction was defined as a reduction in the visual pain score within one hour of drug administration. We excluded non-English articles, articles that measured the impact of diphenhydramine beyond the acute period, and those that used a pain score other than the 10-point visual pain scale. The information sources included PubMed, Google Scholar, Cochrane, PROSPERO, and grey literature (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform) databases for articles published between 1963 and January 2022, along with the articles referenced at the end of the reviews, for the keywords ‘diphenhydramine’, ‘antihistamine’, ‘pain’, and ‘analgesia’. The researchers used the RoB 2 Cochrane risk-of-bias tools for randomised controlled trials. RESULTS We included four studies out of 128,902 involving 438 patients, out of whom 218 received diphenhydramine for pain control. The mean pain score in patients who received diphenhydramine was reduced by 28%; t(6)= -2.879, 95% CI [-2.87 to -0.23], p=0.028. When the baseline pain score was included in the analysis, we noted a reduction of 48% from the initial pain score. The pooled effect size or mean difference in acute pain reduction favouring diphenhydramine, taken from a random-effects model, was -1.53 (95% CI: [-2.35 to -0.70]) using Cohen’s d. CONCLUSION This meta-analysis confirms the analgesic advantages of diphenhydramine and supports its consideration as an adjunct for acute pain management in the ED.