Due to a lack of robust evidence, it is not clear whether gentamicin - an antibiotic given into the ear (intratympanic gentamicin) works to improve symptoms for people with Ménière's disease. It is also not clear whether there are any risks associated with treatment.
Larger, well-conducted studies are needed to identify whether this treatment may be effective, and to assess whether there are any harmful effects.
Further work also needs to be done to find out how best to measure the symptoms of people with Ménière's disease, to assess whether treatments are beneficial or not. This should include the development of a 'core outcome set' - a list of things that should be measured in all studies on Ménière's disease.
What is Ménière's disease?
Ménière's disease is a condition that affects the inner ear. It causes repeated attacks of dizziness or vertigo (a spinning sensation), together with hearing problems, tinnitus (ringing, humming or buzzing noises in the ear) and a feeling of fullness or pressure in the affected ear. It usually affects adults and starts in middle age.
How is Ménière's disease treated?
Oral medications (tablets) are often used as the first treatment for Ménière's disease. If these treatments do not control the symptoms, then a type of antibiotics known as aminoglycosides may be given directly into the ear. Typically this involves an antibiotic called gentamicin. This is most commonly given as an injection through the ear drum.
What did we want to find out?
We wanted to find out:
- whether there was evidence that intratympanic aminoglycosides (including gentamicin) work at reducing the symptoms of Ménière's disease;
- whether this treatment might cause any harm.
What did we do?
We searched for studies that compared any intratympanic aminoglycosides to either no treatment or sham (placebo) treatment.
What did we find?
We found five studies, which included a total of 137 people. They lasted between six months and two years. All of the studies looked at the antibiotic gentamicin.
- More people who received intratympanic gentamicin felt that their vertigo had improved, when compared to people who received no treatment (or a sham treatment). However, the studies were extremely small, so we cannot be sure that the treatment works to improve symptoms.
- When people used a scoring system to rate their vertigo symptoms or the frequency of their vertigo, the ratings were better in those who received intratympanic gentamicin when compared to those who received no treatment (or sham treatment). Again, the studies were so small that we are very uncertain if the treatment is effective.
- The studies included in this review did not provide any information on the risk of serious harms related to the treatment. Other types of studies have shown that this treatment might be associated with potential side effects (such as complete loss of hearing). However, we do not have any information from the studies included in this review on how common these problems are after treatment.
What are the limitations of the evidence?
We have very little confidence in the evidence because most of the studies conducted were very small, and had problems in their conduct, which mean that the results may be unreliable. Larger, well-conducted studies are needed to try and work out how effective the different treatments really are.
How up-to-date is this evidence?
This evidence is up-to-date to September 2022.
The evidence for the use of intratympanic gentamicin in the treatment of Ménière's disease is very uncertain. This is primarily due to the fact that there are few published RCTs in this area, and all the studies we identified enrolled a very small number of participants. As the studies assessed different outcomes, using different methods, and reported at different time points, we were not able to pool the results to obtain more reliable estimates of the efficacy of this treatment. More people may report an improvement in vertigo following gentamicin treatment, and scores of vertigo symptoms may also improve. However, the limitations of the evidence mean that we cannot be sure of these effects. Although there is the potential for intratympanic gentamicin to cause harm (for example, hearing loss) we did not find any information about the risks of treatment in this review.
Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analysis of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.
Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Aminoglycosides are sometimes administered directly into the middle ear to treat this condition. The aim of this treatment is to partially or completely destroy the balance function of the affected ear. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear.
To evaluate the benefits and harms of intratympanic aminoglycosides versus placebo or no treatment in people with Ménière's disease.
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022.
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with a diagnosis of Ménière's disease comparing intratympanic aminoglycosides with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified).
We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome.
We included five RCTs with a total of 137 participants. All studies compared the use of gentamicin to either placebo or no treatment. Due to the very small numbers of participants in these trials, and concerns over the conduct and reporting of some studies, we considered all the evidence in this review to be very low-certainty.
Improvement in vertigo
This outcome was assessed by only two studies, and they used different time periods for reporting. Improvement in vertigo was reported by more participants who received gentamicin at both 6 to ≤ 12 months (16/16 participants who received gentamicin, compared to 0/16 participants with no intervention; risk ratio (RR) 33.00, 95% confidence interval (CI) 2.15 to 507; 1 study; 32 participants; very low-certainty evidence) and at > 12 months follow-up (12/12 participants receiving gentamicin, compared to 6/10 participants receiving placebo; RR 1.63, 95% CI 0.98 to 2.69; 1 study; 22 participants; very low-certainty evidence). However, we were unable to conduct any meta-analysis for this outcome, the certainty of the evidence was very low and we cannot draw any meaningful conclusions from the results.
Change in vertigo
Again, two studies assessed this outcome, but used different methods of measuring vertigo and assessed the outcome at different time points. We were therefore unable to carry out any meta-analysis or draw any meaningful conclusions from the results. Global scores of vertigo were lower for those who received gentamicin at both 6 to ≤ 12 months (mean difference (MD) -1 point, 95% CI -1.68 to -0.32; 1 study; 26 participants; very low-certainty evidence; four-point scale; minimally clinically important difference presumed to be one point) and at > 12 months (MD -1.8 points, 95% CI -2.49 to -1.11; 1 study; 26 participants; very low-certainty evidence). Vertigo frequency was also lower at > 12 months for those who received gentamicin (0 attacks per year in participants receiving gentamicin compared to 11 attacks per year for those receiving placebo; 1 study; 22 participants; very low-certainty evidence).
Serious adverse events
None of the included studies provided information on the total number of participants who experienced a serious adverse event. It is unclear whether this is because no adverse events occurred, or because they were not assessed or reported.