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Home All Specialties Emergency

Diphenhydramine, Sodium Bicarbonate, or Combination for Acute Peripheral Vertigo

byAlex XiangandSimon Pan
November 10, 2025
in Emergency, Neurology, Pharma
Reading Time: 3 mins read
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1. Intravenous diphenhydramine and sodium bicarbonate together are significantly more effective than diphenhydramine alone at reducing the severity of acute peripheral vertigo symptoms.

Evidence Rating Level: 2 (Good)

Study Rundown: Vertigo, the sensation that either oneself or the environment is spinning, is often accompanied by nausea and vomiting and represents a common presentation to emergency departments. Intravenous antihistamines, benzodiazepines, or anticholinergics are used for rapid, short-term control of severe symptoms. However, these medications are associated with an increased incidence of side effects, including drowsiness and fall risk. Intravenous sodium bicarbonate does not cause these side effects and has been used to treat vertigo, possibly through increased inner ear perfusion and medial vestibular nucleus neural inhibition. However, no studies have compared the efficacy of antihistamines and sodium bicarbonate in treating vertigo.

This triple-arm, double-blinded, randomized clinical trial was conducted at the National Taiwan University Hospital’s ED in Yunlin, Taiwan, from January 17 to November 14, 2023. Participants included patients aged 18 years or older who experienced vertigo onset within the past 24 hours.

Overall, this study found that both diphenhydramine and sodium bicarbonate reduce vertigo symptoms, with a significantly greater improvement when the two agents were administered in combination. Groups receiving diphenhydramine had a significantly greater risk of drowsiness, and groups receiving sodium bicarbonate were significantly more likely to complain of injection discomfort. While sodium bicarbonate may be a safer vertigo treatment choice owing to its lower risk of drowsiness, future studies are required to determine its mechanism and identify which peripheral vertigo subtypes it is effective for.

Click here to read this study in JAMA Network Open

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Relevant reading: Comparison of acute vertigo diagnosis and treatment practices between otolaryngologists and non-otolaryngologists: A multicenter scenario-based survey

In-Depth [randomized clinical trial]

It is unclear whether intravenous sodium bicarbonate alone or in combination with diphenhydramine provides better symptom relief than diphenhydramine alone for patients with acute peripheral vertigo. This randomized clinical trial investigated the efficacy and safety of these agents or their combination in treating vertigo symptoms. The primary outcome was the change in vertigo severity at 60 minutes after treatment as measured using a visual analogue scale. 

222 patients were randomized in a 1:1:1 ratio to receive 30 mg of diphenhydramine (group A, M [SD] age = 59.2 [18.3], 28.0% male), 66.4 mEq of sodium bicarbonate (group B, M [SD] age = 53.7 [16.3], 36.5% male), or a combination of both agents (group C, M [SD] age = 61.0 [17.4], 32.9% male). At 60 minutes after treatment, group C had greater improvement in vertigo severity than group A (mean [SD] VAS score, -5.6 [2.1] vs -4.4 [2.7]; P = 0.01). Group B showed similar VAS improvement compared with group A (mean [SD] VAS score, -5.1 [2.2] vs -4.4 [2.7]; P = 0.34) and group C (mean [SD] VAS score, -5.1 [2.2] vs -5.6 [2.1]; P = 0.57). Groups treated with diphenhydramine had a greater chance of experiencing moderate lethargy (group A, 38.7% [29 of 75]; group B, 8.1% [6 of 74]; group C, 30.1% [22 of 73]; P < 0.001). Groups treated with sodium bicarbonate had a greater chance of experiencing injection discomfort (group A, 8.0% [6 of 75]; group B, 17.6% [13 of 74]; group C, 28.8% [21 of 73]; P = 0.004).

Image: PD

©2025 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

Tags: diphenhydramineemergencyneurologyperipheral vertigosodium bicarbonate
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