JAMA Netw Open

Combination therapy bests diphenhydramine alone for acute peripheral vertigo

November 10, 2025

Adding sodium bicarbonate to diphenhydramine may enhance symptom relief and reduce rescue therapy needs in patients with acute peripheral vertigo, though clinicians should weigh injection discomfort with bicarbonate against benefits.

Study details: This triple-arm, double-blind randomized trial (NCT05676216) at a Taiwanese ED enrolled 222 adults with acute peripheral vertigo (<24 hours onset). Patients received IV diphenhydramine (30 mg), sodium bicarbonate (≈66 mEq), or both. Primary outcome was change in vertigo severity on a 10-point visual analog scale (VAS) at 60 minutes; secondary outcomes included nausea, rescue medication use, ED length of stay, and adverse effects.

Results: Combination therapy improved vertigo scores more than diphenhydramine alone (VAS, −5.6 vs. −4.4; P = 0.01) and reduced rescue medication use (17.8% vs. 46.7%; P < 0.001). Sodium bicarbonate alone showed similar efficacy to diphenhydramine (VAS, −5.1 vs. −4.4; P = 0.34). Lethargy was more frequent with diphenhydramine (38.7%) than sodium bicarbonate (8.1%), while injection discomfort was higher with sodium bicarbonate (up to 28.8%). No differences were observed in nausea or ED length of stay.

Source:

Chi CY, et al. (2025, November 3). JAMA Netw Open. Diphenhydramine, Sodium Bicarbonate, or Combination for Acute Peripheral Vertigo: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41196596/