Repositioning maneuvers in benign paroxysmal positional vertigo: how do we improve outcomes?

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder. A series of meetings with clinicians treating BPPV were conducted to seek their views on improving outcomes in patients with BPPV. BPPV is primarily treated by Otolith repositioning maneuvers (ORM) to help to move the otoconia out of the canal and lead it back to the vestibule. Although repositioning maneuvers are effective in BPPV management, some patients experience residual dizziness, postural instability, recurrences, and psycho-emotional consequences after about 1 month after repositioning. An important and useful non-pharmacological intervention for patients with balance disturbances is Vestibular rehabilitation (VR), which includes vestibular adaptation, habituation and substitution, and patient education. Repositioning devices and mastoid vibration could help a subgroup of patients with BPPV who do not respond to conventional management. Betahistine dihydrochloride accelerates the recovery of function of vestibular system by improving blood flow in the inner ear, and normalization of the function of motion sensitive hair cells is faster. Betahistine-treated patients may have faster recovery, lesser recurrence, and longer relief of symptoms. The use of betahistine in combination with maneuvers can help prevent the development of residual dizziness.

Effects of Betahistine on the Development of Vestibular Compensation after Unilateral Labyrinthectomy in Rats

Background: Vestibular compensation (VC) after unilateral labyrinthectomy (UL) consists of the initial and late processes. These processes can be evaluated based on the decline in the frequency of spontaneous nystagmus (SN) and the number of MK801-induced Fos-positive neurons in the contralateral medial vestibular nucleus (contra-MVe) in rats. Histamine H3 receptors (H3R) are reported to be involved in the development of VC. Objective: We examined the effects of betahistine, an H3R antagonist, on the initial and late processes of VC in UL rats. Methods: Betahistine dihydrochloride was continuously administered to the UL rats at doses of 100 and 200 mg/kg/day using an osmotic minipump. MK801 (1.0 mg/kg) was intraperitoneally administered on days 7, 10, 12, and 14 after UL, while Fos-positive neurons were immunohistochemically stained in the contra-MVe. Results: The SN disappeared after 42 h, and continuous infusion of betahistine did not change the decline in the frequency of SN. The number of MK801-induced Fos-positive neurons in contra-MVe significantly decreased on days 7, 10, and 12 after UL in a dose-dependent manner in the betahistine-treated rats, more so than in the saline-treated rats. Conclusion: These findings suggest that betahistine facilitated the late, but not the initial, process of VC in UL rats.

SIMULTANEOUS ESTIMATION, VALIDATION, AND FORCED DEGRADATION STUDIES OF BETAHISTINE DIHYDROCHLORIDE AND DOMPERIDONE IN A PHARMACEUTICAL DOSAGE FORM USING RP-HPLC METHOD

Objective: This study describes the stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous estimation of betahistine dihydrochloride and domperidone in pharmaceutical dosage forms.Methods: The proposed RP-HPLC method was developed using Shimadzu Prominence-i LC-2030 HPLC system equipped with UV detector and chromatographic operation was carried on Shim-pack C18 (250 mm×4.6 mm, 5 μ) column at a flow rate of 1 ml/min and the run time was 10 min. The mobile phase consisted of methanol and water in the ratio of 80:20% v/v and eluents were scanned using a UV detector at 244 nm.Results: The retention time of betahistine dihydrochloride and domperidone was found to be 2.3 and 3.6 min, respectively. A linearity response was observed in the concentration range of 9.6 μg/ml–22.4 μg/ml for betahistine dihydrochloride and 6–14 μg/ml for domperidone, respectively. Limit of detection and limit of quantification for betahistine dihydrochloride were 0.52 μg/ml and 1.58 μg/ml and for domperidone are 0.64 μg/ml and 1.94 μg/ml, respectively.Conclusion: The stability-indicating method was developed by subjecting drugs to stress conditions such as acid and base hydrolysis, oxidation, photo and thermal degradation, and degraded products formed were resolved successfully from samples.

Betahistine dihydrochloride or betahistine mesilate: two sides of the same coin or two different coins

The antivertigo drug betahistine exerts a histamine modulatory action in the vestibular system and the brain. It is marketed both as the dihydrochloride and the mesilate salt in India. We conducted a published literature based systematic review to ascertain differences, in any, between the salt and ester forms of the drug. Search of the Medline database was supplemented by searching through references in full text papers and retrieving summary of product characteristic literature. Although the weight of published evidence is greater for betahistine dihydrochloride, in the absence of head-to-head studies comparing the efficacy of the two formulations in Ménière's disease and other vertigo disorders of vestibular origin, it is not possible to conclude that there are definite differences in this regard. However, potentially relevant differences exist to suggest that the two forms are not interchangeable for the treatment of vestibular dysfunction. Molecular weight comparison indicates that the pill burden would be higher for betahistine mesilate for delivering equivalent doses. There could be ethnically influenced differences in pharmacokinetic behavior. There are concerns of potential long-term DNA toxicity due to mesilate ester contaminants during production of betahistine mesilate, which is not there for the hydrochloride form. Detailed post-marketing surveillance data exists only for the dihydrochloride salt. Otorhinolaryngologists and other physicians seeking to optimize treatment with betahistine should be aware of these differences.