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The closed testing procedure was intended to handle multiple comparison issues between the three arms. Committee for Medicinal Products for Human Use. No patients were involved in setting the research question or the outcome measures, nor were they involved in developing plans for participant recruitment, or the design and implementation of the study. Long term use of Betahistine | Meniere's Disease - Patient Thirdly, they provided diary information within the 90 day assessment period (that is, there was availability of measurements of the primary variable within the period of interest). There are no plans to explicitly involve patients in dissemination. Using the GRADE system, we judged the quality of evidence overall to be low for two outcomes (proportion of patients with improvement and proportion with adverse events).Pooled data showed that the proportion of patients reporting an overall reduction in their vertigo symptoms was higher in the group treated with betahistine than the placebo group: risk ratio (RR) 1.30, 95% confidence interval (CI) 1.05 to 1.60; 606 participants; 11 studies). Betahistine dihydrochloride tablets were over-encapsulated with mannitol and aerosil as filling material. doi: 10.1002/14651858.CD013093.pub2. Exclusion criteria were diagnosis of other central or peripheral vestibular disorders such as vestibular migraine, benign paroxysmal positioning vertigo, paroxysmal brainstem attacks, as well as phobic postural vertigo. The lower panels show the estimated individual incidences per month over time. Betahistine (AS) | healthdirect Am J Transl Res. For each patient, we calculated the median duration and severity of attacks within months seven, eight, and nine (time period of primary interest). Betahistine may be worth trying for people with undiagnosed vertigo Furthermore, we used pure tone audiometry to determine hearing loss (recorded in dB) during bone conduction for test conditions 250 Hz, 500 Hz, 1000 Hz, and 2000 Hz, and to determine the tinnitus intensity (in dB). Benign paroxysmal positional vertigo (BPPV): Causes and treatment Betahistine for symptoms of vertigo - PMC - National Center for Patients were instructed to take six capsules per day (two capsules in the morning, two at noon, and two in the evening). We used a closed testing approach to avoid the adjustment of the significance level because of multiple testing. Hence, patients who prematurely discontinued the study or treatment before month 7 were excluded from the per protocol sample. At the end . Betahistine | Memorial Sloan Kettering Cancer Center Other reasons (for example, a desire for another treatment option such as an operation; or moving abroad) were named in 158 patients. At this site, 410 patients were screened, and 86 of 221 patients randomised (that is, about 40% of all study participants). Table 7 summarises adverse events deemed clinically important. Frequency of clinically important adverse events occurring in nine month treatment period (plus post-treatment adverse events occurring within a three week gap period). doi: 10.1002/14651858.CD008419.pub2. We also performed electronystagmography, including bithermal caloric irrigation to measure caloric nystagmus response, and pure tone audiometry. It is generally safe to take. As secondary endpoints, the trial also studied the treatment effect on vertigo related impairment in quality of life as well as on vestibular and audiological function. Li W, Sun J, Zhao Z, Xu J, Wang H, Ding R, Zhang Y. Firstly, this group included patients for whom no major protocol violations were detected (for example, poor compliance, errors in treatment assignment). Effective at controlling symptoms such as sneezing, itching, watery eyes, and runny nose. Owing to variable methodological rigour and shortcomings in previous trials including the potential risk of bias, the medical treatment of Menieres disease with betahistine (BEMED) trial was designed. 2015 Mar 10;(3):CD008419. For the FAS population as well as the per protocol sample, the percentages of patients with longlasting attacks or more severe attacks did not significantly differ across treatment groups (duration: P=0.348 (FAS), P=0.515 (per protocol); severity: P=0.390 (FAS), P=0.438 (per protocol)). Likewise, these secondary outcomes were defined for the selected ear. Treatment should aim to stop or reduce the number and severity of acute attacks of vertigo, reduce or eliminate tinnitus, and prevent impaired vestibular function and hearing loss. If any of these effects last or get worse, tell your doctor or pharmacist promptly. Diary based secondary efficacy endpoints were the median duration and median severity of evaluated Menieres attacks during months seven to nine within the nine month treatment period. Statistical analyses were performed using the statistical software package R version 3.1.1.54 We used the R packages lme4 (version lme4_1.1-7) to fit frequentist generalised linear mixed effects models,55 56 ordinal to fit cumulative logit models,57 and mice for multiple imputation techniques applied for key secondary efficacy outcomes.52 53 All statistical tests were two sided, and P<0.05 was considered significant. Informed consent for data sharing was not obtained from participants, but the data presented are anonymised and the risk of identification is very low. These may include nausea, upset stomach, vomiting, diarrhea and stomach cramping. It will be less likely to upset your stomach. National Library of Medicine We'll keep an eye on you. Regardless of the cause, this study found that if 100 people with vertigo are treated with betahistine, 60 will report improvement. Unauthorized use of these marks is strictly prohibited. It is used to relieve the symptoms of hay fever (seasonal allergic rhinitis) and hives of the skin (chronic idiopathic urticaria) . The trial also aimed to ascertain the speed of effectthat is, whether the two active doses can be distinguished from each other or from placebo by how quickly reduction in attack frequency is achieved.38 Additionally, the tolerance and adverse events were examined. This work was supported by the German Centre for Vertigo and Balance Disorders (DSGZ), University Hospital Munich, Campus Grosshadern, Munich, Germany. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 8); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. You should seek medical advice in relation to medicines and use only as directed by a healthcare professional. Initial evaluation of the post-treatment frequency of attacks caused by Menieres disease within the first 30 days of treatment (pseudobaseline) showed the three groups to be comparable at the outset (table 2). These may include nausea, upset stomach, vomiting, diarrhea, dry mouth and stomach cramping. A total of 1450 patients were screened for eligibility at 17 outpatient sites; 221 patients were randomised at 14 sites. Selection criteria: About betahistine Who can and cannot take it How and when to take it Side effects Pregnancy, breastfeeding and fertility Taking betahistine with other medicines and herbal supplements Common questions This type of dizziness is thought to originate in the inner ear labyrinth or its neural connections. Betahistine for symptoms of vertigo | Cochrane Side effects reported in this Cochrane review were uncommon and usually mild. Capsules containing the active ingredient were refilled from original pharmacy packaging into vials under sterile conditions and relabelled by the pharmacy of the university hospital of the University of Heidelberg. Primary efficacy analysis on full analysis set, plus use of two varying definitions of Menieres attacks as supportive efficacy analyses. Pilot data from an observational study by Strupp and colleagues36 supported the assumption that the probability to achieve a better result on betahistine than placebo is 0.75. The primary analysis considered time courses for each patient in a longitudinal manner, taking into account patients who did not provide attack information for the three month assessment period at the end of the treatment period. The analysis found no evidence for between treatment differences in mean change scores. A total of 221 eligible patients at 14 study sites were randomly assigned in a 1:1:1 ratio to receive either high dose or low dose betahistine, or placebo for nine months (fig 1). FOIA The NB GLMM has fixed effects for treatment group, time (numerical variable for months one to nine), and treatment by time interaction. Betahistine (Serc, Betaserc) is used by many people to reduce the frequency and severity of these attacks but there is conflicting evidence relating to its effects. MS, JW, CSF, RG, and all investigators of the 14 study sites acquired the data. Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. MethodsThe BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). We saw no significant difference between the three groups concerning treatment duration (Kruskal-Wallis test used as global testing procedure; FAS P=0.824; per protocol P=0.600). The principal model was established by use of data from a previous open non-interventional study36 together with statistical methodology that has been published elsewhere.49. Betahistine - Oral | HealthLink BC This medication may also rarely cause drowsiness. The advice from the neurotologist was simple - just live your life and be grateful that betahistine works for you. Any side effects that persist or outweigh the relief of symptoms of the original condition may warrant that the patient consult their physician to adjust or change the medication. doi: 10.1002/14651858.CD015171.pub2. A key secondary endpoint measured during clinic visits was peripheral vestibular function determined by electronystagmography under caloric irrigation (two test conditions for the right and left ear: 30C for the cool irrigation, 44C for the warm irrigation). While attending a GP update course in Glasgow I was concerned when one of the presenters suggested that, in the light of a BMJ article (BMJ 2016,352:h6816) regarding a German study looking at the efficacy of betahistine treatment for Meniere's disease, that as GPs we should review all our patients taking . TEAEs of severe intensity were reported for 20 (27%), 20 (28%), and 19 (26%) patients in the placebo, low dose betahistine, and high dose betahistine groups, respectively. We review the evidence for the existence of clozapine-induced withdrawal symptoms, and in particular focus on withdrawal-associated psychosis, cholinergic rebound, catatonia and serotonergic discontinuation symptoms. He has a Master of Science in sociology from Portland State University. Based on this target parameter, the recalculated sample size of 46 participants per group (138 in total) will have 80% power to detect the difference between two independent groups using a Mann-Whitney U test with a two sided 5% significance level (nQuery Advisor 7.0). Opioid withdrawal can be dangerous, and symptoms can be severe. Patients experiencing chronic digestive problems may lower their dose to the minimum effective range and by taking betahistine with meals. Objectives We assumed a dropout rate of about 37%. The majority were at high risk of bias, but in some the risk of bias was unclear. To approximate the robust comparison as mentioned at the beginning of this section, we averaged the individual attack rates over the prespecified assessment period (months seven to nine) to derive a (marginal) population based, mean attack rate per 30 days for each treatment arm. We do not capture any email address. Betahistine hydrochloride is a medication indicated for the treatment of Meniere's syndrome, which often results in vertigo, nausea, vomiting, hearing loss and inner ear inflammation. The most commonly reported adverse events leading to drug discontinuation were tinnitus, vertigo, ear discomfort, and nervous system disorders, which were all more commonly reported with high dose betahistine than with low-dose betahistine treatment and placebo. Official answer. Collaborators on behalf of the of BEMED (medical treatment of Menieres disease with betahistine) study group: Michael Strupp, Carolin Simone Fischer, Eike Krause, Robert Grkov, Sabrina Holzapfel, Martin Westhofen, Thomas Lempert, Hubert Lwenheim, Michael v Brevern, Thomas Lenarz, Hans-Christoph Diener, Hermann Hilber, Ines Repik, Trker Basel, Daniel Wei, Dirk Beutner, and Holger A Rambold. Search methods: Sixteen studies including 953 people compared betahistine with placebo. What is betahistine used for? - Drugs.com An NB GLMM (negative binomial mixed effects model) assessed a general decline in the incidence of attacks caused by Menieres disease over the nine 30 day intervals. Other patients were being treated with betahistine and did not want to change or stop treatment (n=93). Hence, sex did not affect the time course of Menieres attacks, nor did it affect the decline in attack rates. Prochlorperazine: medicine to help stop you feeling or being sick - NHS Some nervous system events may also partly be attributable to the underlying condition rather than the medication used to treat it. The doses and placebo were administered continuously for nine months, and investigators observed their effect on the frequency, duration, and severity of acute attacks caused by Menieres disease, vertigo related impairment of quality of life, and vestibular and audiological function. Effects of vestibular rehabilitation, with or without betahistine, on Only 237 (5%) episodes of vertigo were characterised as both an R and P attack. TESAEs reported by more than one patient during the study were vertigo (4.1% of patients in the placebo and high dose betahistine groups) and inguinal hernia and intervertebral disc protrusion (both 2.8% of patients in the low dose betahistine group). See: http://creativecommons.org/licenses/by-nc/3.0/. The decay rate of the daily attack rate (fixed effect for time) on placebo was set to 0.06, and a treatment effect of 0.08 (treatment by time interaction) was chosen. It can be caused by problems in the ear or the brain. We presented the primary results of the BEMED trial and articulated open questions that might guide future studies on treatment options in Menieres disease (for example, planning figures for sample size calculation). Moreover, groups were well balanced with regard to disease duration and age at onset of vertiginous symptoms (data not shown). Patients taking betahistine hydrochloride may experience several hypersensitivity and allergic reactions. The site is secure. Systemic pharmacological interventions for Mnire's disease. 4 5 Annual incidence of the disease in the USA was 15.3 per 100000 people (age adjusted rate).6 The peak age of onset is during the fifth and sixth decade.7. Secondary outcomes assessed during clinic visitsthat is, both the observer-reported outcome and the quality of life scores, were analysed in a descriptive manner. Web appendix 2 provides results of the complete case analyses. Vertigo is a symptom in which individuals experience a false sensation of movement. Betahistine | Prescribing information | Mnire's disease - CKS Clozapine discontinuation withdrawal symptoms in schizophrenia In figure 3, the upper panels show the observed individual profiles of monthly incidences of attacks caused by Menieres disease during the nine month treatment period, stratified by treatment group. The study database was stored in SAS (Unix Version 9.2, SAS Institute). Fexofenadine is an antihistamine. Table 1 shows the demographic and clinical characteristics as well as three total scores on quality of life assessed at the baseline visit of all 221 patients randomised. Pooling of sites within the catchment area of the DSGZ in Munich, which recruited about 40% of all randomised patients, showed no evidence of a centre effect (P=0.542, global likelihood ratio test comparing the main model with the adjusted one (pooled pseudosite Munich yes v no)). Leave 6 to 8 hours between doses. Betahistine is belongs to a group of medications used to treat vertigo associated with Mnire's disease. Abbott did not have any influence on the analyses or interpretation of the data or on the content or form of the manuscript. We report the prespecified efficacy and safety analyses at nine months for the BEMED trial. Explorative, not preplanned efficacy analyses were performed on specific types of vertigo spells: rotatory or postural attacks, and rotatory only attacks. Data collection and analysis: Efficacy and safety of betahistine treatment in patients with Meniere's Web appendix 1 shows a template of the vertigo diary. A second prespecified adjusted analysis explored whether estimated treatment effects varied significantly between age subcategories of trial participants. Firstly, it increases dose-dependent cochlear blood flow,27 mainly via the H3 receptor as an inverse agonist.28 Because betahistine has a strong first pass effect and is metabolised in the liver into three metabolites, not only betahistine but also its major metabolite aminoethylpyridine increases cochlear blood flow.29 Secondly, betahistine increases histamine turnover in the central nervous and vestibular system, also mainly via the H3 receptor. Marginal mean attack rates per month over study assessment periods for each treatment group (FAS population). Both diary based endpoints (attack duration and severity) were reported on an ordinal rating scale by use of predetermined codes (codes for attack duration: 2 (1-20 min), 3 (20-60 min), 4 (60-180 min), 5 (>180 min); codes for attack severity: 1 (mild), 2 (moderate), 3 (severe), 4 (very severe)). Opiates: Definition, Types, Impact, and Risks - Verywell Mind The withdrawal was upheld by a US court of appeals in 1968. . Common questions about betahistine - NHS This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Carpenter JR, Kenward MG. An event was defined as end of treatment before day 241 (start of grey region), according to the prespecified minimum exposure to the treatment regimen defined as per protocol and the corresponding definition of a major protocol deviation. Hence, a total of 220 patients had to be enrolled in the trial. Report / Delete 1 Reply. PMID: 15587054 Abstract A 73-year-old man was admitted because of delirium that had already persisted for 5 days. The results might not hold for patients with other vestibular disorders or taking higher doses of betahistine. 2012 Apr 18;2012(4):CD008675. How betahistine might have an effect in the prophylactic treatment of Menieres disease is so far unknown. Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat. Adjustment for sex effect did not significantly improve the model used for the primary efficacy analysis (P=0.202, global likelihood ratio test). Abstract Background: Vertigo is a symptom in which individuals experience a false sensation of movement. The BEMED trial aimed to determine whether treatment with high or low dose betahistine or placebo differed in effectiveness. It specifically assessed the frequency, duration, and severity of acute attacks caused by Menieres disease during a nine month treatment period. Publication RM03/JH17/MK. They are usually mild and will stop by themselves. Patients were enrolled in the study from 31 March 2008 (first patient, first visit) to 5 November 2013 (last patient, last visit), including a three month follow-up. The full analysis set (FAS) population included all patients randomised (irrespective of whether they were treated or not), and who did not fail to satisfy a major entry criterion. The protocol was approved by local independent ethics committees and was performed in accordance with the Declaration of Helsinki and other applicable guidelines, laws, and regulations. Betahistine may also cause several digestive-related side effects. Symptoms of hives include raised, red, itchy bumps, streaks, or blotches on the skin. Lower panels: Estimated individual trajectories of incidence of attacks per month depending on fixed and random effects after fitting an NB GLMM (that is, conditional estimates resulting from the longitudinal model used for the primary efficacy analysis). 2023 Mar 31;102(13):e33421. The corresponding estimated factors, representing rate ratios compared with placebo, were 1.036 (0.942 to 1.140) and 1.012 (0.919 to 1.114) for the low and high dose groups, respectively (table 3). The basic effect quantity of a U test is the probability to achieve a better result in the experimental arm than in the control arm. Notably, these supportive efficacy analyses demonstrated the robustness of the key results with respect to the definition of the primary endpoint. Most TEAEs were of mild or moderate intensity. NIHR-RP-011-045/DH_/Department of Health/United Kingdom, NCI CPTC Antibody Characterization Program. This manuscript is part of the doctoral thesis of Christine Adrion. What will it do for me? Federal government websites often end in .gov or .mil. The package insert for Serc, a trade name for betahistine, states that patients may experience several gastrointestinal side effects 2. Are there any other medicines to help with my symptoms of Mnire's disease? The key findings of the BEMED trial are as follows: A significant decline of attack rates in each treatment arm was observed over the nine month treatment period, The effects of two different doses of betahistine could not be distinguished from a patient reported effect caused by placebo intervention in terms of the incidence of attacks as well as vestibular and audiological function and quality of life. Objectives: To assess the effects of betahistine in patients with . Accessibility Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function. Eye irritation and palpitations were more commonly reported with high dose betahistine than with low dose betahistine and placebo. Wegner I, Hall DA, Smit AL, McFerran D, Stegeman I. Cochrane Database Syst Rev. Treatment compliance based on drug accountability was not calculated owing to insufficient data quality and a high proportion of missing data. and because "the major report of effectiveness contained deficiencies and misrepresentations" (Sampson, 2003). About betahistine - NHS Cochrane Database Syst Rev. In case of a high proportion of missing values at baseline or at the nine month visit, multiple imputation techniques based on chained equations (the MICE method52 53) assuming MAR were applied within the ANCOVA. Written informed consent was obtained from all patients before initiation of the first study specific procedure. Betahistine as a treatment for vertigo: A systematic review of Below, we reconsider these aspects using the PICO approach (patient, intervention, comparison, outcome) to discuss the strengths and limitations of the BEMED trial. Web appendix 2 shows the definition of the total scores for the dizziness and self-assessment scales. Electing the (number of) Menieres attacks in a given time period as the efficacy endpoint, documented by diaries in the patients natural environment (PRO), runs the risk of having missing or inaccurate information compared with objective measurements such as audiogram or questionnaires.