Management of peripheral vertigo with antihistamines: New options on the horizon

Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibular vertigo symptoms. Agents targeting the H₁ and H₃ receptors have been in clinical use for several decades as single agents. Nonetheless, effective management of vertigo proves elusive as many treatments largely address only associated symptoms, and with questionable efficacy. Additionally, the primary and limiting side effect of sedation is counterproductive to normal functioning and the natural recovery process occurring via central compensation. To address these issues, the timing of administration of betahistine, the mainstay H₃ antihistamine, can be fine-tuned, while bioavailability is also being improved. Other approaches include antihistamine combination studies, devices, physical therapy and behavioural interventions. Recently demonstrated expression of H₄ receptors in the peripheral vestibular system represents a new potential drug target for treating vestibular disorders. A number of novel selective H₄ antagonists are active in vestibular models in vivo. The preclinical potential of SENS-111 (Seliforant), an oral first-in-class selective H₄ antagonist is the only such molecule to date to be translated into the clinical setting. With an excellent safety profile and notable absence of sedation, encouraging outcomes in an induced vertigo model in healthy volunteers have led to ongoing clinical studies in acute unilateral vestibulopathy, with the hope that H₄ antagonists will offer new effective therapeutic options to patients suffering from vertigo.