Supplementary Material for: Betahistine in Ménière’s Disease or Syndrome: A Systematic Review

Background: Ménière’s disease is characterized by recurrent episodes of vertigo, hearing loss, and tinnitus, often with a feeling of fullness in the ear. Although betahistine is thought to be specifically effective for Ménière’s disease, no evidence for a benefit from the use of betahistine exists, despite its widespread use. Reassessment of the effect of betahistine for Ménière’s disease is now warranted. Search Methods: We searched for randomized controlled trials (RCTs) in the Central Register of Controlled Trials (CENTRAL), Ovid Medline, Ovid Embase, CINAHL, Web of Science, Clinicaltrials.gov, ICTRP, and additional sources for published and unpublished trials, in which betahistine was compared to placebo. Data Collection and Analysis: Our outcomes involved vertigo, significant adverse effect (upper gastrointestinal discomfort), hearing loss, tinnitus, aural fullness, other adverse effects, and disease-specific health-related quality of life. We used GRADE to assess the quality of the evidence. Main Results: We included 10 studies: 5 studies used a crossover design and the remaining 5 were parallel-group RCTs. One study with a low risk of bias found no significant difference between the betahistine groups and placebo with respect to vertigo after a long-term follow-up period. No significant difference in the incidence of upper gastrointestinal discomfort was found in 2 studies (low-certainty evidence). No differences in hearing loss, tinnitus, or well-being and disease-specific health-related quality of life were found (low- to very low-certainty of evidence). Data on aural fullness could not be extracted. No significant difference between the betahistine and the placebo groups (low-certainty evidence) could be demonstrated in the other adverse effect outcome with respect to dull headache. The pooled risk ratio for other adverse effect in the long term demonstrated a lower risk in favor of placebo over betahistine. Conclusions: High-quality studies evaluating the effect of betahistine on patients with Ménière’s disease are lacking. However, one study with low risk of bias found no evidence of a difference in the effect of betahistine on the primary outcome, vertigo, in patients with Ménière’s disease when compared to placebo. The main focus of future research should be on the use of comparable outcome measures by means of patient-reported outcome measures.

背景：梅尼埃病（Ménière’s disease）以反复发作的眩晕、听力损失与耳鸣为主要特征，常伴随耳胀满感。尽管倍他司汀（betahistine）被认为对梅尼埃病具有特异疗效，但即便其临床应用广泛，目前仍无证据证实其治疗获益。当前亟需重新评估倍他司汀治疗梅尼埃病的效果。
检索方法：本研究于对照试验中央注册库（Central Register of Controlled Trials, CENTRAL）、Ovid Medline、Ovid Embase、CINAHL、Web of Science、Clinicaltrials.gov、ICTRP及其他已发表与未发表试验来源中，检索以倍他司汀对比安慰剂的随机对照试验（randomized controlled trial, RCT）。
数据收集与分析：本研究的结局指标涵盖眩晕、严重不良反应（上消化道不适）、听力损失、耳鸣、耳胀满感、其他不良反应以及疾病特异性健康相关生活质量。我们采用GRADE对证据质量进行评估。
主要结果：本研究共纳入10项研究，其中5项采用交叉设计，剩余5项为平行组随机对照试验。1项偏倚风险较低的研究显示，长期随访后，倍他司汀组与安慰剂组在眩晕结局上无显著差异。2项研究（低确定性证据）表明，上消化道不适的发生率无显著差异。在听力损失、耳鸣、健康状况及疾病特异性健康相关生活质量方面均未发现显著差异（证据确定性为低至极低）。耳胀满感相关数据无法提取。在钝性头痛相关的其他不良反应结局中，倍他司汀组与安慰剂组未显示出显著差异（低确定性证据）。长期随访中其他不良反应的合并风险比显示，安慰剂组的风险低于倍他司汀组。
结论：目前缺乏评估倍他司汀对梅尼埃病患者疗效的高质量研究。但1项偏倚风险较低的研究证实，与安慰剂相比，倍他司汀对梅尼埃病患者的主要结局指标——眩晕，并无显著疗效差异。未来研究的核心应聚焦于采用统一的患者报告结局指标（patient-reported outcome measures, PROMs）作为标准化结局测量工具。