Key messages

• Betahistine might reduce the number of vertigo attacks, intensity of vertigo, and lead to symptomatic improvement according to global judgement of patients with Ménière’s disease, but the certainty of the evidence is low.
• Betahistine probably does not have important adverse effects.

What is the evidence.
See evidence matrix  in Epistemonikos later

We found four systematic reviews [3],[4],[5],[6] including 12 primary studies relevant for our question [7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18], all of them randomized controlled trials.

What types of patients were included*

Some trials did not use the American Academy of Otolaryngology –Head and Neck Surgery guidelines’ criteria for Ménière’s disease [1]. In consequence, some systematic reviews did not include them into their analysis. In order to present direct evidence, these are presented in this table, but were not used to estimate the effect of benefits in the summary of findings table.

Six trials specified the inclusion of patients with clinical Ménière’s disease [8],[10],[11],[12],[14],[17].

One of the trials included patients with progressive episodic vertigo [9], two included patients with two or three months of peripheral vertigo [7],[13] and one with recurrent vertigo defined as two or more vertigo attacks in the last month [15]. Two trials did not specify the inclusion criteria [16],[18].

What types of interventions were included*

All trials compared betahistine against placebo.
Two trials used 4 mg six times per day [11],[16]. Two used 8 mg every 8 hours [12],[14], two used 16 mg every 8 hours [9],[15] and one trial two times per day [17]. Other trials used 12 mg every 8 hours [7], 18 mg two times per day [8], 24 mg every 8 hours [18] and every 12 hours [10]. One trial allowed a dose up to 48 mg per day [13].

What types of outcomes
were measured

Outcomes, according to how they were grouped in the identified systematic reviews were:

• Number, intensity and duration of acute attacks of vertigo
• Hearing
• Severity of tinnitus
• Perception of aural fullness
• Functional impairment and disability
• Overall wellbeing and quality of life
• Side effects of betahistine
• Vestibular function tested with objective tests
• Opinion on the response of vertigo symptoms
• Overall clinical evaluation of the change in patient`s condition
• Patients dropping out from study.

To whom this evidence does and does not apply

• The results of this summary apply to patients with Ménière’s disease who have symptoms of vertigo.
• In this summary we used the trials including patients who met the clinical definition of Ménière’s disease; however, the reviews assessing a broader set of patients with vertigo, arrived to similar conclusions, so it is reasonable to extrapolate the results to these patients. 

• The results of this summary apply to patients with Ménière’s disease who have symptoms of vertigo.
• In this summary we used the trials including patients who met the clinical definition of Ménière’s disease; however, the reviews assessing a broader set of patients with vertigo, arrived to similar conclusions, so it is reasonable to extrapolate the results to these patients. 

• Since the certainty of the evidence is low for reducing the number of vertigo attacks, vertigo intensity and global symptomatic improvement, it is difficult to make a balance between risk and benefits for betahistine in patients with Ménière’s disease. On the other hand, it probably does not have adverse effects.

• Betahistine has a relatively high cost. However, it is difficult to make a balance between costs and benefits, due to the uncertainty about the latter.

• Variability in decision-making for this intervention can be expected. Patients who put more emphasis on an uncertain benefit may be inclined to use it. Those who put more value on the certainty of the evidence or costs, are likely to lean against its use.
• One factor to consider among physicians is that during their clinical experience they have historically used betahistine and there is heterogeneity in existing recommendations in clinical practice guidelines. This is likely to contribute to even greater variability in decision-making.

Differences between this summary and other sources

• The conclusions of this summary are consistent with two of the four included systematic reviews [4],[5], and partially concordant with the others.
• These results are also consistent with clinical practice guidelines on Ménière’s disease from Spain [19], Mexico [20] and France [21], and partially concordant with Philippine`s guidelines, which strongly recomend its use [22]. American AAO-NHS guidelines are still in process.

• The probability of the conclusions of this summary changing with future trials is high because of the existing uncertainty about the benefits of betahistine.
• We identified at least two trials, not included in systematic reviews, that could help to clarify the evidence regarding this topic [23],[24].
• We searched for ongoing studies on the World Health Organization  International Clinical Trials Registry Platform and found at least one unpublished trial on this topic [25].