A triple blind, placebo controlled, randomised controlled trial of betahistine dihydrochloride in the treatment of primary tinnitus.

OBJECTIVES: To evaluate the effectiveness of betahistine in the treatment of primary tinnitus. DESIGN: To evaluate the effectiveness of betahistine in the treatment of primary tinnitus. SETTING: Universidade estadual Paulista Julio de Mesquita Filho, Botucatu Medical School, São paulo, Brazil. PARTICIPANTS: Adult patients with primary tinnitus who had not undergone treatment for tinnitus in the last 6 months were included. Patients with profound sensorineural deafness, hearing aid users and patients with metabolic, neurological, psychiatric or decompensated cardiovascular diseases were excluded. STUDY GROUPS: in the betahistine group, patients received betahistine 24 mg every 12 h for 90 days; in the control group, patients received placebo tablets every 12 h for 90 days. MEAN OUTCOME MEASURES: Primary outcome measure: Tinnitus Handicap Inventory (THI). SECONDARY OUTCOME MEASURES: Clinical Global Impression Improvement (CGI-I) and a question of 'Yes' or 'No' to participants about their perception of improvement in symptoms. RESULTS: Of 284 participants initially identified, 62 were randomised (betahistine group n = 31; control group n = 31). Median age (IQR) 54 (48-60) years, with a balanced number of men and women. There was no difference in THI outcome between the study groups (median difference, -2 points; 95% CI, -8 to 6 points); the THI after the intervention was a median (IQR) 4 (-4 to 14) lower points in the betahistine group, and a median (IQR) 2 (-6 to 10) in the control group. There was no statistical difference in secondary outcome measures. Adverse events were mild and there was no statistical difference between groups. CONCLUSIONS: Betahistine dihydrochloride was ineffective in the treatment of primary tinnitus in adults.

Betahistine add-on therapy for treatment of subjects with posterior benign paroxysmal positional vertigo: a randomized controlled trial / Terapia adjuvante de betaistina para o tratamento de indivíduos com vertigem posicional paroxística benigna posterior: um ensaio clínico randomizado

Abstract Introduction Benign paroxysmal positional vertigo is a common vestibular disorder that accounts for one fifth of hospital admissions due to vertigo, although it is commonly undiagnosed. Objective To evaluate the effects of betahistine add-on therapy in the treatment of subjects with posterior benign paroxysmal positional vertigo. Methods This randomized controlled study was conducted in a population of 100 subjects with posterior benign paroxysmal positional vertigo. Subjects were divided into the Epley maneuver + betahistine group (group A) and Epley maneuver only (group B) group. Subjects were evaluated before and 1-week after the maneuver using a visual analog scale and dizziness handicap inventory Results One hundred subjects completed the study protocol. The Epley maneuver had an overall success rate of 95% (96% in group A; 94% in group B, p= 0.024). Groups A and B had similar baseline visual analog scale scores (6.98 ± 2.133 and 6.27 ± 2.148, respectively, p= 0.100). After treatment, the visual analog scale score was significantly lower in both groups, and was significantly lower in group A than group B (0.74 ± 0.853 vs. 1.92 ± 1.288, respectively, p= 0.000). The change in visual analog scale score after treatment compared to baseline was also significantly greater in group A than group B (6.24 ± 2.01 vs. 4.34 ± 2.32, respectively, p= 0.000). The baseline dizziness handicap inventory values were also similar in groups A and B (55.60 ± 22.732 vs. 45.59 ± 17.049, respectively, p= 0.028). After treatment, they were significantly lower in both groups. The change in score after treatment compared to baseline was also significantly greater in group A than group B (52.44 ± 21.42 vs. 35.71 ± 13.51, respectively, p= 0.000). Conclusion The Epley maneuver is effective for treatment of benign paroxysmal positional vertigo. Betahistine add-on treatment in posterior benign paroxysmal positional vertigo resulted in improvements in both visual analog scale score and dizziness handicap inventory.

Resumo Introdução A vertigem posicional paroxística benigna é um distúrbio vestibular comum, responsável por um quinto das internações hospitalares por vertigem, embora seja comumente não diagnosticada. Objetivo Avaliar os efeitos da terapia adjuvante com betaistina no tratamento de indivíduos com vertigem posicional paroxística benigna posterior. Método Este estudo randomizado controlado foi feito em uma população de 100 indivíduos com vertigem posicional paroxística benigna posterior. Os indivíduos foram divididos nos grupos: manobra de Epley + betaistina (grupo A) e manobra de Epley apenas (grupo B). Os indivíduos foram avaliados antes e uma semana após a manobra por meio da escala visual analógica EVA e do questionário dizziness handicap inventory. Resultados Cem indivíduos completaram o protocolo do estudo. A manobra de Epley demonstrou uma taxa de sucesso global de 95% (96% no grupo A; 94% no grupo B, p = 0,024). Os grupos A e B tiveram escores basais semelhantes na EVA (6,98 ± 2,133 e 6,27 ± 2,148, respectivamente, p = 0,100). Após o tratamento, o escore na EVA foi significantemente menor em ambos os grupos e foi menor no grupo A do que no grupo B (0,74 ± 0,853 vs. 1,92 ± 1,288, respectivamente, p = 0,000). A mudança no escore da EVA após o tratamento em comparação com a linha basal também foi significativamente maior no grupo A do que no grupo B (6,24 ± 2,01 vs. 4,34 ± 2,32, respectivamente, p = 0,000). Os valores basais no dizziness handicap inventory também foram semelhantes nos grupos A e B (55,60 ± 22,732 vs. 45,59 ± 17,049, respectivamente, p = 0,028). Após o tratamento, eles foram significantemente menores em ambos os grupos. A mudança no escore após o tratamento em comparação com a linha basal também foi significantemente maior no grupo A do que no grupo B (52,44 ± 21,42 vs. 35,71 ± 13,51, respectivamente, p = 0,000). Conclusão A manobra de Epley é eficaz no tratamento da vertigem posicional paroxística benigna. O tratamento complementar com betaistina na vertigem posicional paroxística benigna posterior resultou em melhoria tanto no escore da EVA quanto no do dizziness handicap inventory.

Betahistine alleviates benign paroxysmal positional vertigo (BPPV) through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

BACKGROUND: Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. METHODS: We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. RESULTS: After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. CONCLUSION: Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

Betahistine add-on therapy for treatment of subjects with posterior benign paroxysmal positional vertigo: a randomized controlled trial.

INTRODUCTION: Benign paroxysmal positional vertigo is a common vestibular disorder that accounts for one fifth of hospital admissions due to vertigo, although it is commonly undiagnosed. OBJECTIVE: To evaluate the effects of betahistine add-on therapy in the treatment of subjects with posterior benign paroxysmal positional vertigo. METHODS: This randomized controlled study was conducted in a population of 100 subjects with posterior benign paroxysmal positional vertigo. Subjects were divided into the Epley maneuver + betahistine group (group A) and Epley maneuver only (group B) group. Subjects were evaluated before and 1-week after the maneuver using a visual analog scale and dizziness handicap inventory RESULTS: One hundred subjects completed the study protocol. The Epley maneuver had an overall success rate of 95% (96% in group A; 94% in group B, p =  0.024). Groups A and B had similar baseline visual analog scale scores (6.98 ±â€¯2.133 and 6.27 ±â€¯2.148, respectively, p = 0.100). After treatment, the visual analog scale score was significantly lower in both groups, and was significantly lower in group A than group B (0.74 ±â€¯0.853 vs. 1.92 ±â€¯1.288, respectively, p = 0.000). The change in visual analog scale score after treatment compared to baseline was also significantly greater in group A than group B (6.24 ±â€¯2.01 vs. 4.34 ±â€¯2.32, respectively, p = 0.000). The baseline dizziness handicap inventory values were also similar in groups A and B (55.60 ±â€¯22.732 vs. 45.59 ±â€¯17.049, respectively, p = 0.028). After treatment, they were significantly lower in both groups. The change in score after treatment compared to baseline was also significantly greater in group A than group B (52.44 ±â€¯21.42 vs. 35.71 ±â€¯13.51, respectively, p = 0.000). CONCLUSION: The Epley maneuver is effective for treatment of benign paroxysmal positional vertigo. Betahistine add-on treatment in posterior benign paroxysmal positional vertigo resulted in improvements in both visual analog scale score and dizziness handicap inventory.

Betahistine alleviates benign paroxysmal positional vertigo (BPPV) through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway

BACKGROUND: Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. METHODS: We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. RESULTS: After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. CONCLUSION: Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

Betahistine in the Treatment of Peripheral Vestibular Vertigo: Results of a Real-Life Study in Primary Care.

The present research was carried out with the objective to establish the clinical effect and safety of betahistine (48 mg daily), for the management of peripheral vestibular vertigo, in patients treated by primary care physicians in Colombia. An observational prospective cohort study was conducted including patients older than 15 years with clinical diagnosis of peripheral vestibular vertigo who were candidates to be treated with betahistine (48 mg daily). A sample size of 150 individuals was calculated, and weekly follow-ups were planned for 12 weeks. Rotatory movement sensation, loss of balance, and global improvement scale from 0 to 100 points were evaluated. Complete improvement was defined when the patient reached a level of 100 points. We calculated average weekly improvement, cumulative incidence of complete improvement, incidence rate of complete improvement, and the probability of complete improvement as a function of time. After the first week, the average improvement was 56.6 points (95% confidence interval [CI]: 50.4-62.7). At the end of week 12, it was 89.3 points (95% CI: 86.5-92.2). Sixty-one percent of the patients had achieved complete improvement at the end of the second week. After the sixth week, the percentage of cumulative improvement was 72%, and after 12 weeks of follow-up, the cumulative incidence of complete improvement was 73% (95% CI: 65%-80%). Based on the follow-up times, a complete improvement incidence rate of 16 cases per 100 people/week was calculated (95% CI: 13-19). We concluded that Betahistine (48 mg daily) has a positive effect, controlling the symptoms associated with benign paroxysmal vertigo, with an adequate safety profile.

Comparação da bioequivalência entre duas formulações de dicloridrato de betaistina 24 mg comprimidos em voluntários sadios após a administração de dose única / Comparison of the bioequivalence between two formulations of betahistine hydrochloride 24 mg tablets in healthy volunteers after a single dose dministration

A biodisponibilidade de uma dose única de dicloridrato de betaistina em comprimidos de 24 mg produzidos por Aché Laboratórios Farmacêuticos S.A. foi comparada com o medicamento referência (à época do estudo) dicloridrato de betaistina 24 mg (Labirin®, Apsen Farmacêutica S.A.). Um estudo de dose única, randomizado, aberto, cruzado em dois períodos foi realizado em 34 voluntários brasileiros, sadios, de ambos os gêneros. Dezenove coletas de sangue foram realizadas durante 24 horas. As amostras foram mantidas congeladas até o momento de análise. As concentrações plasmáticas de ácido 2-piridilacético, um metabólito da betaistina, foram determinadas utilizando um método de CLAE-EM/EM validado. Os intervalos com 90% de confiança para concentração plasmática máxima (Cmáx) e área sob a curva (ASC0-t) foram determinados utilizando os dados após transformação logarítmica. As formulações teste e referência foram consideradas bioequivalentes se os intervalos com 90% de confiança para a média geométrica da razão teste/referência ficassem compreendidos na faixa de 80% a 125%. Os intervalos com 90% de confiança para as razões das médias geométricas para Cmáx foi 105,18% (97,31%-113,70%) e para ASC0-t foi 99,33% (95,55%-103,26%). Em conclusão, os comprimidos de dicloridrato de betaistina 24 mg testados (Aché Laboratórios Farmacêuticos S.A.) foram bioequivalentes aos comprimidos de Labirin® 24 mg, de acordo com taxa e extensão de absorção.

Dicloridrato de betaistina na síndrome vestibular periférica canina / Betahistine dihydrochloride in canine peripheral vestibular syndrome

A síndrome vestibular periférica é uma condição clínica comum em cães. Várias doenças podem causar essa síndrome. Entretanto, sua patofisiologia ainda é pouco conhecida. As alterações clínicas geralmente são autolimitantes, a recuperação pode ser longa e, em casos crônicos, os déficits neurológicos podem ser irreversíveis. Em medicina veterinária, há poucas opções terapêuticas. Na Medicina, o dicloridrato de betaístina é amplamente utilizado. Essa medicação foi empregada em seis cães com síndrome vestibular periférica. Os resultados mostraram melhora clínica com sete a dez dias de tratamento e recuperação quase completa entre vinte e trinta dias. Este trabalho descreve a utilização da betaistina em cães com síndrome vestibular periférica, a rápida melhora clínica e ausência de efeitos adversos. Os resultados obtidos parecem justificar o uso de dicloridrato de betaistina na terapia de distúrbios vestibulares periféricos em animais de companhia.

Vestibular disease is a common syndrome in small animals that may resulst of central or peripheral disease. The pathophysiology of peripheral vestibular syndrome is unknown, however it can be related to an abnormal dynamic of endolymphatic fluid or neuritis of the vestibular portion of the VIII cranial nerve. The recovery of neurological sings is slow and, in chronic cases, the neurological deficits can be irreversible. In veterinary medicine, thera are few medical options to treat this condition, however, in Medicine, betahistine dihydrochloride is used to treat peripheral vestibular disorders. These drug was used in four dogs with vestibular syndrome. The results showed clinical improvement in 7 to 10 days of treatment and completed recovery in 20 to 30 days, followed by the cure. One year after the treatment, the dogs did not have recurrence of the syndrome. This report shows the use of betahistine dihydrochloride in dogs with peripheral vestibular syndrome, with rapid clinical recover, without laboratorial abnormalities or recurrence of the clinical signs .The results encourage the use of betahistine dihydrochloride in the treatment of peripheral vestibular disorders in small animals.

Dicloridrato de betaistina na síndrome vestibular periférica canina / Betahistine dihydrochloride in canine peripheral vestibular syndrome

A síndrome vestibular periférica é uma condição clínica comum em cães. Várias doenças podem causar essa síndrome. Entretanto, sua patofisiologia ainda é pouco conhecida. As alterações clínicas geralmente são autolimitantes, a recuperação pode ser longa e, em casos crônicos, os déficits neurológicos podem ser irreversíveis. Em medicina veterinária, há poucas opções terapêuticas. Na Medicina, o dicloridrato de betaístina é amplamente utilizado. Essa medicação foi empregada em seis cães com síndrome vestibular periférica. Os resultados mostraram melhora clínica com sete a dez dias de tratamento e recuperação quase completa entre vinte e trinta dias. Este trabalho descreve a utilização da betaistina em cães com síndrome vestibular periférica, a rápida melhora clínica e ausência de efeitos adversos. Os resultados obtidos parecem justificar o uso de dicloridrato de betaistina na terapia de distúrbios vestibulares periféricos em animais de companhia.(AU)

Vestibular disease is a common syndrome in small animals that may resulst of central or peripheral disease. The pathophysiology of peripheral vestibular syndrome is unknown, however it can be related to an abnormal dynamic of endolymphatic fluid or neuritis of the vestibular portion of the VIII cranial nerve. The recovery of neurological sings is slow and, in chronic cases, the neurological deficits can be irreversible. In veterinary medicine, thera are few medical options to treat this condition, however, in Medicine, betahistine dihydrochloride is used to treat peripheral vestibular disorders. These drug was used in four dogs with vestibular syndrome. The results showed clinical improvement in 7 to 10 days of treatment and completed recovery in 20 to 30 days, followed by the cure. One year after the treatment, the dogs did not have recurrence of the syndrome. This report shows the use of betahistine dihydrochloride in dogs with peripheral vestibular syndrome, with rapid clinical recover, without laboratorial abnormalities or recurrence of the clinical signs .The results encourage the use of betahistine dihydrochloride in the treatment of peripheral vestibular disorders in small animals.(AU)