2021/03/23 by Sean Holmes, Anil K. Lalwani, Gauri Mankekar · 5 citations
Medicine · Neuroscience · #Adverse effect #Allergic Rhinitis and Sensitization #Alternative medicine #Anesthesia #Antihistamine #Betahistine #Disease #Endolymphatic hydrops #Glaucoma and retinal disorders #Internal medicine #Medicine #Meniere's disease #Otorhinolaryngology #Pediatrics #Placebo #Surgery #Vertigo #Vestibular and auditory disorders
paper · pdf · doi:10.1002/lary.29535
published in The Laryngoscope 131(12), 2639-2640 (Wiley)
openalex publication_date 2021/03/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Ménière's disease (MD) or endolymphatic hydrops is an idiopathic disorder commonly affecting adults between 40 and 60 years of age. Medical therapy is focused on treatment of acute episodes, prophylaxis, and mitigation of disease progression during the interval between attacks. Patients who receive no improvement after lifestyle changes are frequently treated with diuretic or betahistine or antihistamine therapies. Betahistine, a partial H1 receptor agonist and potent H3 receptor antagonist, is widely used in Europe and rest of the world in the treatment of MD. However, lacking Food and Drug Administration approval, it is unavailable in the United States. Betahistine is known to increase cochlear blood flow and well tolerated at doses of 16 to 48 mg daily with no reported significant adverse events. It is contraindicated in patients with asthma, renal or cardiac disease, and allergies or hypersensitivities to the medication. In this Triological Society Best Practice, we review the current literature to determine whether betahistine is effective in the treatment of MD. The majority of reviews on betahistine as a medical treatment for MD did not arise until the early 2000s. The first Cochrane review on betahistine for MD by Burton et al. was published in 2001.1 Seven trials were recruited for a total of 243 patients. Only one trial used American Academy of Otolaryngology and Head Neck Surgery (AAO-HNS) guidelines to establish a diagnosis of MD using accepted criteria, while others reported their own criteria for diagnosis. All studies compared betahistine hydrochloride with placebo. Doses ranging from 16 mg to 36 mg daily were divided into various dosing regimens, except one trial with 24 mg betahistine thrice daily. In this review, long-term follow-up data up to 40 weeks were reported by several trials, in contrast to previously noted studies with a lack of adequate follow-up. Overall, authors noted that due to the heterogeneity of the trials with lack of uniformity in dosing/timing and methods of assessment of outcome measures, a statistical summary was not possible. Of note, a trial by Mira et al. from 2003, included in the review, reported statistically significant reduction in vertigo attack frequency and intensity scores from 1 month onwards and significant improvement in balance in both the placebo and betahistine groups. Nauta et al. included 14 randomized, double-blind, placebo-controlled clinical studies in their meta-analysis to compare betahistine with placebo for treatment of MD/vestibular vertigo.2 A total of 1,038 patients were randomized within each of these studies to include 506 patients to the betahistine group, 500 to the placebo, and 32 patients whose assigned group was not reported. The main outcome measure was response to treatment of symptoms of vertigo. Eleven of 14 studies showed a positive effect in favor of betahistine with improvement of vertigo symptoms. Four of those 11 demonstrated statistically significant decrease in vertigo symptoms and also highly significant calculated average odds ratios. For all the studies reported in this meta-analysis, the range of daily dosing of betahistine was 24 mg to 48 mg and treatment duration was between 14 days to 3 months. The authors concluded that benefit/risk ratio is positive for this safe and effective medical therapy in treatment of MD. Murdin et al. published a Cochrane review in 2016 on betahistine for symptoms of vertigo, which included 17 randomized controlled trials (RCTs) for a total of 1025 participants randomized to either betahistine or placebo.3 Their main outcome measure was the proportion of patients with reduction in vertigo symptoms. They noted a pooled risk ratio of 1.30 in favor of betahistine; however, the statistical heterogeneity of their data was high and follow-up period was 3 months—they stated that outcomes should be interpreted with caution. Dosage ranged from 16 mg to 48 mg daily in their included RCTs. The rates of adverse events were the same for both groups, without any major events. The authors concluded that betahistine is well tolerated and low risk, and that in patients suffering from vertigo there may be positive effect in reduction of vertigo symptoms. In June 2020, a meta-analysis was published by Devantier et al. on betahistine in the treatment of patients with MD.4 They were only able to identify one RCT that matched inclusion criteria, the BEMED trial published in 2016 by Adrion et al. This multicenter, double-blind RCT was conducted across 14 German tertiary referral centers. Two-hundred twenty-one patients with MD per 1995 AAO-HNS guidelines were included in the trial under three arms: placebo, high-dose betahistine (24 mg thrice daily), and low-dose betahistine (24 mg twice daily). The key findings of the trial were a significant decline in attack rates in all groups, but no clear evidence that placebo compared to high or low dose of histamine reduced the number of vertigo attacks. There were no safety concerns with betahistine, even with high doses. Devantier et al. went on to report that overall certainty of evidence was low, and further that there is no RCT evidence to support that betahistine provides significant or adequate symptomatic relief for patients with MD. They also cited the need for further RCTs to consolidate the effect of betahistine in MD. A study published in December 2020 by Liu et al. reported an RCT with 66 patients comparing three patient groups: betahistine group, vestibular rehabilitation therapy group, and control group that received no treatment.5 Betahistine dosing was 12 mg thrice daily for a total study duration of 1 month. There was a statistically significant improvement in Dizziness Handicap Index and fall index scores for the betahistine group compared with control and for the vestibular rehabilitation group compared to control; however, improvements in the vestibular rehab were greater than betahistine. This may be explained by the fact that vestibular rehabilitation integrates visual, proprioceptive, and residual vestibular function to build patient strength and confidence to maintain balance. The authors conclude that both betahistine and vestibular rehabilitation can improve the quality of life and reduce the risk of falling in patients with MD. Though some studies show benefit, there is absence of high-quality data demonstrating the efficacy of betahistine in the treatment of MD. Despite mixed results, it remains popular due to a very low-risk profile. Definitive large-scale RCTs with standardized diagnostic criteria, dosing regimens, and long-term follow-ups are required to assess the efficacy of betahistine in MD. Level I and II evidence was utilized to formulate this best practice. Of note, there is a possible risk of bias in all the studies, as some of the patients included would be diagnosed with vestibular migraine today. The authors thank Dr Nathan, Chairman, Department of Otolaryngology and Head Neck Surgery, LSU Health, Shreveport, for her encouragement and support.