Betahistine Dihydrochloride Research Articles

Multiple Bccs after Lisinopril Intake – Significant Connections to The Drug Related Photo- (Nitroso)-Carcinogenesis in The Context of Oncopharmacogenesis

An 80-year-old female presented to the dermatology department due to an atrophic lesion in the area of the nasal apex, dating for the past 5-6 years. Moreover, there was a slowly developing tumor-like growth in her left temporal region, initially noticed 1-2 years ago. Over the last month, the formation began to bleed upon light touch. Furthermore, there was another lesion in the sacral area with an irregular hyperpigmented edge, also dating back 1-2 years. The patient denied having any allergies or family history of skin malignancies. Regarding comorbidities, she underwent cholecystectomy in 2016. She has been managing arterial hypertension with lisinopril dehydrate 10 mg once daily for the past 10 years. Additionally, she has been treating vertigo with a daily intake of betahistine dihydrochloride 16 mg for the same duration. She is also taking spironolactone 25 mg once daily at noon and diosmin 600 mg once daily at noon both for the past two months (prior to the consultation). The patient presented with a request for physical evaluation of the lesions and further therapeutic approach to be established.

The Utility of Betahistine Dihydrochloride, a Structural Analog of Histamine, in Clozapine-associated Daytime Sedation: A Case Series

The Utility of Betahistine Dihydrochloride, a Structural Analog of Histamine, in Clozapine-associated Daytime Sedation: A Case Series

USE OF BETASERCA IN PATIENTS WITH HD WITH COCHLEOVESTIBULAR DISORDERS

Betahistine dihydrochloride is a synthetic drug that has the ability to bind to H1 histamine receptors, which are embedded in the neuroreceptor cells of the inner ear. It has a powerful stimulating effect by increasing the release of neurotransmitters (histamine) from the nerve endings of the inner ear receptor cells into the synapse. The neurotransmitter acts on the precapillary sphincters, causing vasodilation of the vessels of the inner ear, increasing their permeability and thereby normalizing intralabyrinthine pressure, i.e. eliminating hydrops.

The Epley Maneuver versus Betahistine in Treatment of Benign Paroxysmal Positional Vertigo

Background: Benign paroxysmal positional vertigo (BPPV) is considered the most common cause of vertigo. The necessity for early and effective management resulted in the improvement of the patient’s life quality. The objective was to compare the efficacy between Epley’s maneuver and betahistine dihydrochloride in BPPV treatment. Patients and Methods: A prospective follow-up comparative study on 60 patients with BPPV, who diagnosed with a positive Dix–Hallpike test, were divided equally and randomly into two groups; Group “A” treated with Epley’s maneuver and Group “B” treated with betahistine dihydrochloride. The efficacy of each modality was assessed, regarding the sense of vertigo and its associated symptoms, data of vertigo scales as the Visual Analog Scale (VAS), and Dizziness Handicap Inventory (DHI). Results: There were 23 males (38.33%), and 37 females (61.66%), with mean age (54 ± 7.521) years. The total vertigo improvement was (78.33%); being (93.33%) in group “A” and (63.33%) in group “B”, nausea and vomiting symptoms improvement was (76.66%) in group “A”, and (70%) in group “B”. The baseline VAS score in Group “A” (7.69 ± 1.235 SD) and in Group “B” (6.35 ± 3.267 SD) after treatment improved to 0.56 ± 0.731 SD and 1.86 ± 1.375 SD, respectively, as well as the baseline DHI value in Group “A” (51.86 ± 23.583 SD) and in Group “B” (49.37 ± 18.152 SD) then improved to 2.31 ± 3.986 and 7.98 ± 9.512 SD, respectively. Conclusions: The Epley maneuver was more effective and “statistically significant” in relieving vertigo, and both the VAS and DHI scales compared to betahistine, while regarding associated nausea and vomiting symptoms, it shows no statically significant difference.

Ведение пациента с жалобами на головокружение на первичном приеме

Vertigo and balance disorders are one of the most common causes of patients seeking medical help. Vertigo and balance disorders study primarily consists of the following: complaint report, anamnestic data and neurovestibular study. Currently, an algorithm is used based on the identification of three vestibular syndromes: acute, recurrent and chronic, as well as on the analysis of vertigo triggers and concomitant symptoms. Primarily, it is important to determine which vestibular syndrome is acute, recurrent or chronic at the first patient visit with vertigo and balance disorders. Besides, using the otoneurological examination methods is essential for determining the presence or absence of signs concerning the central nervous system disorder or the labyrinth. At the same time, it should be understood that the nervous system disorders accompanied by vertigo can pose a particular danger to the patient and should be excluded first of all. For the treatment and rehabilitation of patients with vertigo, individual selection of therapy and vestibular rehabilitation programs is most effective, taking into account the origin of vestibular disorder, the progression severity, as well as the age, physical and emotional condition. Vestibular rehabilitation can significantly reduce the vertigo severity and improve resistance indicators in patients with vestibular disorders. To improve vestibular compensation, it is advisable to use drug therapy with betahistine dihydrochloride, 48 mg per day, in a modified-release dosage form for better adherence. KEYWORDS: dizziness, balance disorder, acute vestibular syndrome, chronic vestibular syndrome, recurrent vestibular syndrome, betahistine, neurovestibular study FOR CITATION: Amelin A.V., Lilenko S.V., Zamergrad M.V., Guseva A.L., Zaitseva O.V., Voronov V.A., Demidenko D.Yu., Koreshkina M.I., Ovchinnikov D.A. Patient management with complaints of vertigo at the first visit. Russian Medical Inquiry. 2023;7(10):658–665 (in Russ.). DOI: 10.32364/2587-6821-2023-7-10-8.

Efficacy and Safety of a Fixed-Dose Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg in the Treatment of Patients with Vestibular Vertigo: An Individual Patient Data Meta-Analysis of Randomised, Double-Blind, Controlled Clinical Trials

Background and ObjectiveThe source data of four individual randomised, double-blind, reference- and/or placebo-controlled clinical trials with virtually identical study design were pooled for the present meta-analysis. The main objective was to further evaluate the efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in comparison to various other antivertigo treatments in patients suffering from central and/or peripheral vestibular vertigo.MethodsAdult male and female outpatients were subjected to a 4-week treatment with the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg, cinnarizine (20 mg, 50 mg), dimenhydrinate (40 mg, 100 mg), betahistine dimesylate (12 mg), betahistine dihydrochloride (16 mg) and placebo, respectively. The primary efficacy endpoint was the reduction of a validated mean vertigo score (MVS), a composite score of 12 individual vertigo symptoms, the intensities of which were each evaluated by the patients on a 5-point visual analogue scale. For analysis of primary and further secondary efficacy endpoints, baseline-adjusted analysis of covariance (ANCOVA) was used to calculate adjusted least squares means (LSM) with associated two-sided 95% confidence intervals (CIs) for the difference in MVS reductions between treatment groups. Moreover, various sensitivity analyses, responder and subgroup analyses as well as descriptive analyses with respect to safety/tolerability of the treatments were conducted.ResultsOf 795 randomised patients, 779 belonged to the intent-to treat (ITT) and 723 to the per-protocol (PP) population. The main efficacy analysis was based on the ITT population (mean age 52.1 years, 61% female). The mean decrease of the MVS from baseline to Week 4 in the cinnarizine/dimenhydrinate group (−1.10) proved to be significantly larger than in any of the comparator groups. LSM differences for comparators versus the fixed combination ranged between 0.16 (95% confidence interval (CI) 0.03; 0.30, p = 0.017) for cinnarizine 20 mg and 0.60 (95% CI 0.42; 0.78; p < 0.001) for betahistine dimesylate 12 mg in favour of the fixed combination. Furthermore, after 4 weeks of treatment, 74 patients (24.7%) in the cinnarizine/dimenhydrinate group were completely symptom free (MVS = 0), a significantly greater proportion than in any of the comparator groups. Sensitivity analyses showed that baseline characteristics such as age, sex, duration of vertigo and antivertigo pretreatment had only a very minor and clinically non-relevant impact on the efficacy results regarding the primary efficacy outcome. Subgroup analyses with respect to age groups (< 65 years/≥ 65 years) and sex showed no significant differences in efficacy within any of the treatment groups. All treatments were well tolerated. A total of 55 patients (6.9%) reported 75 non-serious adverse events (AEs), and 19 patients (2.4%) discontinued the study prematurely because of AEs. Nearly 95% of the patients (cinnarizine/dimenhydrinate group: 97.9%) rated the tolerability of the study medications as either “good” or “very good”.ConclusionThe findings of the present meta-analysis indicate that the fixed combination of cinnarizine and dimenhydrinate is a safe and potentially superior treatment option for patients suffering from central and/or peripheral vestibular vertigo, as compared to current standard treatments such as cinnarizine, dimenhydrinate or betahistine given alone in monotherapy.

Does the use of betahistine dihydrochloride affect positional nystagmus?

Aim: In this study, we aimed to investigate the effect of betahistine dihydrochloride (BD) use on positional nystagmus as an objective criterion for the diagnosis of benign paroxysmal positional vertigo (BPPV).Methods: The retrospective study included 59 patients (15 males, 44 females) who were aged between 18 and 80 years and referred with suspected BPPV to the otorhinolaryngology clinic of the Istanbul Training and Research Hospital. Only patients who had no central pathology on oculomotor tests were included. Of the patients included, those not using BD were classified as Group I and those using BD medication (24 mg/day) within the last 48 hours as Group II. The positional nystagmus latency, duration, and slow-phase velocity (SPV) values were compared using videonystagmography.Results: There was no significant difference between the two groups in terms of oculomotor gains (p&amp;gt;0.05). While there was no difference between the two groups in terms of positional nystagmus latency and SPV values, nystagmus duration was found to be significantly longer in Group II. Conclusion: Although the BD use appears to prolong the duration of nystagmus in BPPV, it does not affect the other parameters of nystagmus, including SPV, and the prolonged duration is still within normal limits. Positional nystagmus can be investigated in patients with a history of suspected BPPV and BD prescription.

Investigation of inhibitive performance of Betahistine dihydrochloride on mild steel in 1 M HCl solution

This study evaluated the corrosion retardation of mild steel with the use of Betahistine dihydrochloride drug as a sustainable inhibitor in HCl solution and various techniques like weight loss measurements, electrochemical analysis was used to understand the inhibition process. The thermodynamic and adsorption parameters were calculated and discussed on the inhibition behaviour. The corrosion inhibition (% IE) gave a sharp rise with the increased concentration of the Betahistine dihydrochloride drug and reduced efficiency was observed with increased temperature and increased immersion time. Approximately 96% corrosion inhibition efficiency was attained with optimized conditions of 1500 ppm of Betahistine dihydrochloride, 2 h, 1 M HCl at 298 K temperature. Inhibitor adsorption to mild steel abided by the Langmuir adsorption isotherm. Electrochemical impedance spectroscopy revealed the reduction in the value of constant phase element, dip in the values of double-layer capacitance and increase in the charge transfer resistance with increased concentration of Betahistine dihydrochloride drug. Furthermore, potentiodynamic polarization experiments substantiated the mixed type of behaviour. The techniques like scanning electron microscopy, atomic force microscopy, along with ultraviolet–visible spectroscopy, fourier transform infrared spectroscopy, were employed for surface morphology and theoretical models like quantum chemical and molecular dynamics simulations authenticated the experimental observation.

Current aspects of the treatment of different types of vertigo

Dizziness is one of the most frequent complaints of patients in daily clinical practice. The prevalence of vertigo increases significantly in older patients. In most cases, vertigo is caused by pathology of the peripheral vestibular system: benign paroxysmal positional vertigo, vestibular neuronitis, Meniere’s disease. Episodes of recurrent vestibular vertigo without hearing loss can be associated with vestibular migraine, a diagnosis of which remains low in our country. Modern treatment regimens have been developed for patients with various causes of vertigo and unsteadiness. High effectiveness is achieved with a comprehensive approach to the management of patients with vertigo, which includes vestibular exercises, psychological training, and medications that help to reduce the severity and frequency of vertigo attacks and improve vestibular compensation. Many studies have shown high efficacy of the low-dose combination drug cinnarizine 20 mg + dimenhydrinate 40 mg for the treatment of peripheral and central vertigo, which is well tolerated and does not delay vestibular compensation. The efficacy of the low-dose combination drug cinnarizine + dimenhydrinate and betahistine dihydrochloride was compared in the treatment of patients with unilateral vestibular neuronitis, Meniere’s disease, and other diseases of the peripheral and central vestibular system. Studies have shown no less efficacy of the combined drug cinnarizine + dimenhydrinate in the treatment of Meniere’s disease than of betahistine, a more pronounced improvement in vestibular function in the treatment of vestibular neuronitis with the combined drug than with betahistine. For patients with peripheral vestibulopathy of various etiologies, treatment with the combination drug was more effective than therapy with betahistine.

Interventions for Menière’s disease: an umbrella systematic review

ObjectivesTo systematically review the efficacy of interventions for Menière’s disease (MD) to report clinical implications of the results and to identify areas for future valuable research.MethodsIn line with the Preferred...

A comparative study on the response to Epley’s maneuver and betahistine dihydrochloride management among patients with benign paroxysmal positional vertigo

The objective of this study is to evaluate the effectiveness of Epley’s maneuver and Betahistine dihydrochloride on the improvement of patients from BPPV and to comparing the outcome of the use of Betahistine dihydrochloride with the outcome of the use of Epley’s maneuver. This is a prospective and comparative randomized study in Basra Teaching Center of Otolaryngology in which fifty patients were included in this study their age range between (42-65) years, all of them complaining from BPPV. These patients divided into two groups. The first group was treated by Epley’s maneuver and the second group was treated by oral intake of Betahistine dihydrochloride tablet. All patients evaluated at the end of this period by presence or relieving from symptoms and by positive or negative Dix-Hallpike test. A 50 patients were 33 males (66%) and 17 females (34%) and the mean age value for all the patients were in the sixth decade (56.5) years. The improvement from vertigo symptom was statistically significant for the two groups and it was also significant when comparing the two groups which was better in first group and the improvement from associated symptoms like nausea and vomiting and headache was significantly different between the two groups and it was better in the second group.

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.

Pharmacokinetics and Dose Proportionality of Betahistine in Healthy Individuals

Betahistine dihydrochloride is widely used to reduce the severity and frequency of vertigo attacks associated with Ménière’s disease. Betahistine is an analogue of histamine, and is a weak histamine H1 receptor agonist and potent histamine H3 receptor antagonist. The recommended therapeutic dose for adults ranges from 24 to 48 mg given in doses divided throughout the day. Betahistine undergoes extensive first-pass metabolism to the major inactive metabolite 2-pyridyl acetic acid (2PAA), which can be considered a surrogate index for quantitation of the parent drug due to extremely low plasma levels of betahistine. The aim of the present investigation was to assess the pharmacokinetics and dose proportionality of betahistine in Arabic healthy adult male subjects under fasting conditions. A single dose of betahistine in the form of a 8, 16, or 24 mg tablet was administered to 36 subjects in randomized, cross-over, three-period, three-sequence design separated by a one week washout period between dosing. The pharmacokinetic parameters Cmax, AUC0–t, AUC0–∞, Tmax, and Thalf were calculated for each subject from concentrations of 2-PAA in plasma, applying non-compartmental analysis. The current study demonstrated that betahistine showed linear pharmacokinetics (dose proportionality) in an Arabic population over the investigated therapeutic dose range of 8–24 mg.

Betahistine, prevents kindling, ameliorates the behavioral comorbidities and neurodegeneration induced by pentylenetetrazole

A seizure may occur because of the imbalance between glutamate and gamma-aminobutyric acid (GABA). Recurrent seizures induce some cognitive problems, such as, depression, learning and memory deficits, and neurodegeneration. Histamine is an appropriate therapeutic target for epilepsy via its effect on regulating neurotransmitter release. Also, evidence indicates the effect of histamine on neuroprotection and alleviating cognitive disorders. An ideal antiepileptic drug is a substance, which has both anticonvulsant effects and decreases the comorbidities that are induced by repeated seizures. Betahistine dihydrochloride (betahistine) is a structural analog of histamine. It acts as histamine H1 receptor agonist and H3 receptor antagonist, which enhances histaminergic neuronal activities. In the present study, we examined the effect of betahistine administration on seizure scores, memory deficits, depression, and neuronal loss induced by pentylenetetrazole (PTZ). Eight- to ten-week-old BALB/c male mice (20–25 g) received betahistine, 1, and 10 mg/kg daily from 7 days before the onset of PTZ-induced kindling until the end of the establishment of the kindling. We found that betahistine prevented generalized tonic–clonic seizures induction and diminished forelimb clonic seizures intensity. Also, it decreased cell death in the hippocampus and cortex, ameliorated the memory deficit and depression induced by PTZ in the kindled animals. Altogether, these results indicate that pretreatment and repetitive administration with betahistine exerts antiepileptogenic and anticonvulsant activity. These findings might be due to the neuroprotective impact of betahistine in the hippocampus and cortex.

Conductometric determination of Betahistine dihydrochloride and Heptaminol hydrochloride using silver nitrate

A simple, precise and cost effective conductometric method was developed for determination of betahistine dihydrochloride and heptaminol hydrochloride in pure form and pharmaceutical formulations. The method is based on the precipitation of chloride ions present in cited drugs with silver ions, yielding silver chloride, the conductance of the solution is measured as a function of the volume of titrant. Effect of solvent, reagent concentration, temperature were studied and evaluated. The suggested method was applied for determination of betahistine dihydrochloride and heptaminol hydrochloride in pure forms and pharmaceutical preparations. The described procedure allowed the determination of betahistine dihydrochloride and heptaminol hydrochloride in the range of 2-10mg/ml and 2-13mg /ml respectively.The molar ratio was (2:1),(1:1) (drug:reagent) between betahistine dihydrochloride and heptaminol hydrochloride with silver nitrate respectively. The suggested procedure was applied successfully to the analysis of these drugs in their pharmaceutical formulations, and the results obtained were in agreement with those given by the official methods

Mining electronic health records to identify influential predictors associated with hospital admission of patients with dementia: an artificial intelligence approach

BackgroundEarly prediction of the outcomes of dementia is important and challenging. This study aimed to identify influential predictors from primary care electronic health records that can robustly predict whether patients with dementia will be admitted to hospital or remain under GP care. MethodsHealth records of patients with dementia were collected from general practice (GP) and hospital data in Wales between 1980 and 2015. These records were linked at individual patient level via the Secure Anonymised Information Linkage databank. The GP records of each patient were selected 1 year before diagnosis up to hospital admission. An artificial intelligence technique, neural network with entropy regularisation (a multilayer feedforward neural network whose weights between input layer and the first hidden layer were regularised by an entropy metric into the fitness function during training process) was used to automatically identify the most influential predictors from initial GP read codes, sex, and age. 10-fold cross validation was used to assess the predictive performance of the identified signals. Findings52·5 million individual records of 59 298 patients (20 674 men, 38 624 women) with dementia were used. 30 178 were admitted to hospital and 29 120 remained with GP care. More men were admitted to hospital than stayed with GP care (11 233 vs 9441), whereas more women stayed with GP care than were admitted (19 679 vs 18 945). From the 54 649 initial event codes, the ten most important signals identified for admission for dementia were two diagnostic events (nightmares, essential hypertension), five medication events (betahistine dihydrochloride, ibuprofen gel, simvastatin, influenza vaccine, calcium carbonate and colecalciferol chewable tablets), and three procedural events (third party encounter, social group 3—skilled, blood glucose raised). They performed significantly above chance to predict admission to hospital with sensitivity of 0·758 (95% CI 0·731–0·785), specificity 0·759 (0·71–0·808), precision 0·766 (0·735–0·797), and negative predictive value 0·751 (0·741–0·761). Linear regression with all raw features yielded values of 0·286 (0·26–0·313), 0·804 (0·792–0·816), 0·487 (0·463–0·511), and 0·633 (0·615–0·651), respectively, and with ten identified features yielded values of 0·684 (0·679–0·691), 0·712 (0·705–0·718), 0·747 (0·738–0·754), and 0·644 (0·64–0·651). InterpretationOutperforming traditional methods, the artificial intelligence technique provides an effective means of identifying influential clinical signals to predict hospital admission of patients with dementia significantly above chance. FundingHealth Data Research UK Wales and Northern Ireland Site, National Centre for Population Health and Wellbeing Research (CA02), Major Project of National Social Science Foundation of China (16ZDA0092), Guangxi University Digital ASEAN Cloud Big Data Security and Mining Technology Innovation Team.

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.

Vestibular vertigo treatment in a polymorbid patient

Many physicians have difficulty managing patients with vertigo. Incorrect routine diagnoses are frequently made in patients with peripheral vestibulopathy, which makes therapy fail. Most cases of vestibular vertigo are caused by peripheral vestibular disorders (otolithiasis, hydrops, neuronitis). Rehabilitation maneuvers are effective in the treatment of benign paroxysmal positional dizziness; salt-free diet, diuretics, and betahistine dihydrochloride are for MОniПre’s disease (syndrome); vestibular rehabilitation is for vestibular neuronitis. Betahistine dihydrochloride is most effective among all the medicines used in different causes of vestibular vertigo, including that of unclear origin. The paper gives the positive experience with betahistine made in Russia for vestibular vertigo.

Treatment of vertigo in elderly patients with chronic cerebrovascular disease

Dizziness can be caused by different problems in elderly patients; the possibilities of drug therapy are limited; betahistine dihydrochloride is most commonly used. Objective : to investigate the efficiency and safety of combination therapy with mexidol and betahistine in patients with vertigo according to the global assessment scale for treatment efficiency. Patients and methods . The investigation enrolled 89 elderly patients (mean age, 73.7 years) with chronic cerebrovascular disease and complaints of dizziness. Neurological, otoneurological (the orthostatic test, the forced hyperventilation test, the Dix–Hallpike test, the Tinetti test, and the visual vertigo analogue scale), somatic, cognitive and emotional statuses were evaluated in all the patients. The patients were randomized into two groups. A study group included patients who took betahistine 48 mg/day, intravenous Mexidol® 5.0 ml for 10 days, then 375 mg tablets daily for 50 days; a comparison group consisted of patients who used only betahistine 48 mg/day for 60 days. The efficiency of treatment in both groups was evaluated using the global scale on day 60 of therapy, by taking into account the opinion of a physician and a patient. Results . In the elderly patients, vertigo was caused by several problems in the majority (75%) of cases. The combined (betahistine + mexidol) treatment group showed a more significant (more than double) reduction in the symptoms of vertigo than the comparison group. Conclusion . In elderly patients with chronic cerebrovascular disease and vertigo, combined therapy with betahistine and mexidol, which has neuroprotective properties, improves the results of treatment.

Menière's disease: combined pharmacotherapy with betahistine and the MAO-B inhibitor selegiline-an observational study.

Since oral betahistine has a very high first-pass effect (ca. 99%), metabolized by monoamine oxidases (MAO), the benefits of a high-dosage betahistine monotherapy were compared with those of a lower dosage of betahistine in combination with the MAO-B inhibitor (MAO-B) selegiline on the frequency of acute attacks of vertigo in patients with Menière's disease (MD). Thirteen adults aged 40-75years (mean 58.9years; six females) had initially been treated with a high dosage of betahistine dihydrochloride for at least 1year. Under this therapy, all of them had ≤ 1 attack for ≥ 3months prior to the combination pharmacotherapy. Subsequently, they received 5mg/day selegiline and the dosage of betahistine was reduced to about one tenth and then individually adjusted to the dosage needed to achieve the same treatment response (≤ 1 per 3months, observational period of at least 6months). The initial dosage for the long-term "titration" of the attacks of vertigo was 9-80 24-mg tablets/day (mean 37.3), i.e. 216-1920mg/day (mean 895.4mg/day). After the combination with selegiline, the dosage needed to achieve the same benefit for ≥ 3months was 3-36 24-mg tablets (mean 8.5), i.e., 72-864mg/day [mean 204.9mg/day, p < 0.001 (paired t test)]. One patient transiently stopped the treatment with selegiline, another one reduced the dosage to 2.5mg/day and the attacks re-occurred after 2-4weeks. Six out of 13 patients reported transient fullness of the head during the combined treatment; in 2 of them this went away when they switched to 2.5mg bid. In the longer term (> 9months), one patient had to increase the selegiline dosage to 5mg bd, one patient stopped the treatment with selegiline. The achievement of the same clinical effect with a significantly lower (about 1/5) dosage of betahistine can be explained by the inhibition of the MAO-B by selegiline leading to higher serum concentrations of betahistine. This approach is in line with recent developments to bypass the first-pass effect of betahistine by transbuccal or intranasal application. Despite the substantial methodological limitations of such an observational study, this combined pharmacotherapy could be an alternative to a high-dosage monotherapy with betahistine of MD.