A Comprehensive Monograph on Betahistine (DB06698): Pharmacology, Clinical Evidence, and Regulatory Status

Executive Summary

Betahistine is a small molecule drug, classified as a structural analogue of histamine, that is widely prescribed for the symptomatic treatment of Ménière's disease and vestibular vertigo. First registered in Europe in 1970, it is now approved in over 80 countries and has been administered to more than 130 million patients. Its therapeutic rationale is based on a complex and dual mechanism of action: it functions as a weak partial agonist at histamine H1 receptors and as a potent antagonist or inverse agonist at histamine H3 receptors. This dual activity is believed to improve microcirculation in the inner ear, reduce endolymphatic pressure, and centrally modulate neuronal activity within the vestibular nuclei.

Despite its long history and extensive global use, Betahistine is at the center of a significant clinical paradox. Its therapeutic efficacy remains a subject of considerable debate, with high-quality, large-scale randomized controlled trials often failing to demonstrate a statistically significant superiority over placebo at standard therapeutic doses. This stands in stark contrast to its established position in clinical practice in many parts of the world and its favorable long-term safety profile, which is characterized by generally mild and manageable adverse effects.