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Medwave 2018 Mar-Abr;18(2):e7187 doi: 10.5867/medwave.2018.02.7187

�Son efectivos los diur�ticos en la enfermedad de M�ni�re?

Are diuretics effective for M�ni�re`s disease?

Andr�s Rosenbaum, Mat�as Winter

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Abstract

INTRODUCTION
M�ni�re`s disease is an inner ear disorder characterized by episodes of spontaneous vertigo, fluctuating hearing loss and tinnitus. Diuretics have been widely used for the treatment of attacks, but there is controversy about their effectiveness.

METHODS
To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach.

RESULTS AND CONCLUSIONS
We identified three systematic reviews including nineteen studies overall, of which four were randomized trials. We concluded it is not clear whether diuretics lead to a symptomatic improvement of vertigo or an objective decrease in hearing loss in patients with M�ni�re`s disease, because the certainty of the evidence is very low.

Problem

Ménière`s disease is an inner ear disorder characterized by episodes of spontaneous vertigo, fluctuating hearing loss and tinnitus. The American Academy of Otolaryngology and Head and Neck Surgery (AAO-HNS) has created guidelines to define the diagnosis, including two episodes of vertigo greater than 20 minutes, sensorineural hearing loss confirmed by audiometry, added to tinnitus or aural fullness [1]. However, these guidelines are not universally accepted. Pathophysiologically, Ménière`s disease is secondary to an increase in endolymphatic pressure in the inner ear, whose cause is idiopathic. The attacks of this disorder occur on average between 6 to 11 months per year [2].
The ideal treatment aims to reduce the number and severity of vertigo attacks, to reduce hearing loss and tinnitus associated with the attacks, to alleviate chronic symptoms and to prevent the progression of the disease in terms of hearing and balance. While no treatment has met all of these goals, diuretics are frequently used. Different diuretics act by different mechanisms, but all of them would reduce volume and pressure of endolymph, either by increasing clearance or decreasing production. Despite the above, there is controversy regarding the efficacy of this treatment in Ménière’s disease.

Methods

To answer the question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others, to identify systematic reviews and their included primary studies. We extracted data from the identified reviews and reanalyzed data from primary studies included in those reviews. With this information, we generated a structured summary denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos) using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies when it is possible, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

It is not clear whether the use of diuretics leads to a symptomatic improvement of vertigo or to an objective decrease in hearing loss in Ménière`s disease, because the certainty of the evidence is very low.
The use of diuretics in Ménière`s disease is probably associated with minimal adverse effects.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We identified three systematic reviews [3],[4],[5] including nineteen studies overall [6],[7],[8],[9],[10], [11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21], [22],[23],[24], of which four were randomized trials [8],[15],[17],[20]. One trial [20] used isosorbide as an intervention, which is not considered as a diuretic. Another trial [8] did not compare the intervention against placebo, but against betahistine. Both trials were excluded from the analysis. This table and the summary in general are based on the two relevant trials [15],[17], since the observational studies did not increase the certainty of the existing evidence or provide additional relevant information.
What types of patients were included*	Both trials used criteria different to AAO-HNS [1] to define Ménière´s disease [15],[17].
What types of interventions were included*	The trials used hydrochlorothiazide at a dose of 25 mg every 8 hours [15] and hydrochlorothiazide plus triamterene (50 mg/ 25 mg) 2 capsules every 48 hours [17]. Both trials compared the intervention against placebo [15],[17].
What types of outcomes were measured	The outcomes, according to how they were grouped in the identified systematic reviews, were: Number and severity of vertigo attacks Changes in hearing loss Intensity of tinnitus Changes in the perception of aural fullness Functional disability Global changes in wellbeing and quality of life Adverse effects of the treatment The average follow-up was between 4 and 31.7 months.

* The information about primary studies is extracted from the systematic reviews identified, unless otherwise specified.

Summary of Findings

The information on the effects of diuretics for Ménière`s disease is based on two randomized trials involving 63 patients overall [15],[17].

Both trials reported symptomatic improvement in vertigo, changes in hearing loss and adverse effects. None of the identified reviews could conduct a meta-analysis of the identified trials. The summary of findings is the following:

It is not clear whether the use of diuretics leads to a symptomatic improvement of vertigo in Ménière's disease, because the certainty of the evidence is very low.
It is not clear whether the use of diuretics leads to an objective improvement of hearing loss in Ménière's disease, because the certainty of the evidence is very low.
The use of diuretics in Ménière's disease is probably associated with minimal adverse effects. The certainty of the evidence is moderate.

Other considerations for decision-making

To whom this evidence does and does not apply

The conclusions of this summary apply to patients with Ménière`s disease who present with symptoms of vertigo and hearing loss.
All of the trials included in this summary used inclusion criteria different form the AAO-HNS definition [1], so they may not correspond the clinical definition of Ménière`s disease consistent with international guidelines.

About the outcomes included in this summary

The outcomes included in the table are those considered critical for decision-making, according to the opinion of the authors of this summary.
There could be effects on other outcomes such as tinnitus and aural fullness, but they were not reported in the systematic reviews identified.

Balance between benefits and risks, and certainty of the evidence

It is not possible to make an adequate balance between the risks and benefits of diuretics in Ménière's disease due to the uncertainty about the benefits.
On the other hand, diuretics probably have few or no adverse effects in the dose used in Ménière's disease.

Resource considerations

Diuretics are generally low cost drugs.
However, it is not possible to make a balance between costs and benefits due to the uncertainty about the latter.

What would patients and their doctors think about this intervention

Variability in decision-making regarding this intervention can be expected. Patients who put more value on the uncertain benefit could lean in favor of its use. Those who put more value on the certainty of the evidence, the costs or the adverse effects, are likely to lean against it.
One factor to consider is diuretics have been used frequently by clinicians, especially in the early stages of the disease. In addition, there is heterogeneity in existing recommendations in clinical guidelines. This would probably lead to even greater variability in decision-making.

Differences between this summary and other sources

This summary presents information concordant with two of the three systematic reviews evaluated. The Cochrane review [3] did not identify studies of sufficient quality that could be included. The second review [4] concluded the use of diuretics could be beneficial in Ménière's disease, more to reduce the frequency of vertigo attacks than to improve hearing loss. The third review concluded diuretics reduce the symptoms of vertigo, without evidence in the reduction of hearing loss and tinnitus [5].
We did not identify international guidelines widely recognized in this topic. However, Mexican otorhinolaryngology society guidelines [25] are consistent with these results, referring to the systematic reviews previously discussed. The American AAO-NHS guidelines on Ménière are currently being developed.

Could this evidence change in the future?

The likelihood of future research changing the conclusions of this summary is high because of the uncertainty of the existing evidence.
We did not identify clinical trials on this topic that have not been included in systematic reviews.
We performed a search in the World Health Organization's clinical trials platform and did not identify ongoing trials.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Diuretics for Ménière's disease

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier.

After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

This article is part of the Epistemonikos Evidence Synthesis project. It is elaborated with a pre-established methodology, following rigorous methodological standards and internal peer review process. Each of these articles corresponds to a summary, denominated FRISBEE (Friendly Summary of Body of Evidence using Epistemonikos), whose main objective is to synthesize the body of evidence for a specific question, with a friendly format to clinical professionals. Its main resources are based on the evidence matrix of Epistemonikos and analysis of results using GRADE methodology. Further details of the methods for developing this FRISBEE are described here (http://dx.doi.org/10.5867/medwave.2014.06.5997)

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

Potential conflicts of interest

The authors do not have relevant interests to declare.

Licencia Creative Commons

Esta obra de Medwave est� bajo una licencia Creative Commons Atribuci�n-NoComercial 3.0 Unported. Esta licencia permite el uso, distribuci�n y reproducci�n del art�culo en cualquier medio, siempre y cuando se otorgue el cr�dito correspondiente al autor del art�culo y al medio en que se publica, en este caso, Medwave.

Edici�n Julio 2022

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