NIHR Signal Steroid injections into the inner ear may be safe for treating Ménière’s disease

Published on 13 June 2017

Injecting steroids into the space behind the ear drum may be a safer alternative to injections of gentamycin for treating Ménière’s disease. This disease is marked by severe attacks of dizziness and balance problems.

This NIHR-funded trial randomised 60 people with Ménière’s disease who experienced severe attacks of vertigo and had not responded to standard treatment. They were randomly chosen to receive either the corticosteroid methylprednisolone or the antibiotic gentamicin. Participants were followed for two years.

Both were very effective at stopping or reducing symptoms by about 90%. Few side effects were reported in either group.

Gentamicin works by permanently damaging the inner ear function that is concerned with balance, and rarely can cause deafness. Because of this, specialist healthcare professionals may prefer to use of methylprednisolone instead.

Steroid injections into the inner ear may be safe for treating Ménière’s disease

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Why was this study needed?

Ménière’s disease is an inner ear condition that can cause attacks of dizziness, balance problems (vertigo), nausea and vomiting, ringing in the ears (tinnitus) and hearing loss. An estimated one in 1,000 people in the UK have Ménière's disease.

In most people with Ménière's disease, attacks of vertigo can be reduced with a low salt diet, lifestyle changes and the drug betahistine.

In those who experience severe and frequent attacks of vertigo, injecting gentamicin through the eardrum into the middle ear can help. This benefit is achieved through its toxic effects on the parts of the inner ear involved with balance. Gentamicin injections can also cause attacks of vertigo and hearing loss.

Steroids have also been used to treat Ménière’s disease, because unlike gentamicin, they do not damage inner ear function. However, little evidence is available to compare the effectiveness of these approaches.

What did this study do?

The participants had Ménière's disease in one ear, and severe attacks of vertigo that had not responded to standard treatment.

Two middle ear injections were given, two weeks apart. Participants were assessed for vertigo symptoms, balance and hearing at baseline (0 months) and at one, two, six, 12, 18 and 24 months.

If vertigo returned then additional injections were given: either the same drug or switching to the other drug as chosen by a separate unblinded clinician (the patient and other clinicians remained blinded).  

This study did not have a placebo control group, so it is possible that any reduction in attacks of vertigo could be part of the fluctuating course of Ménière’s disease rather than a true effect of either treatment. The small number of participants means the study was underpowered for some results.

What did it find?

  • The average number of vertigo attacks decreased by 90% in the methylprednisolone group (from 16.4 attacks in the six months before treatment to 1.6 in the final six months of follow-up) and 87% in the gentamicin group (from 19.9 attacks to 2.5). The difference was not statistically significant.
  • Two thirds (67%) of people in the methylprednisolone group and a similar proportion (63%) in the gentamicin group had no attacks of vertigo between 18 and 24 months after treatment.
  • The total number of injections per patient was 2.7 (SD1.7) in the gentamicin group and 3.7 (SD2.5) in the methylprednisolone group.Two patients in the methylprednisolone group were deemed treatment failures and received gentamicin.
  • Both groups also had substantial improvements in tinnitus and dizziness.
  • Though inner ear function tests were worse in people who received gentamicin, there were no differences between the groups on questionnaires about balance.
  • Hearing ability did not change in either group compared to baseline.
  • Three people in each group reported mild adverse events, mostly minor ear infections.

What does current guidance say on this issue?

The NICE 2012 Clinical Knowledge Summary on Ménière’s disease  recommends healthcare professionals should consider prescribing betahistine (initially 16 mg three times a day) to reduce the frequency and severity of attacks of hearing loss, tinnitus and vertigo.

It adds that some people with severe, poorly-controlled Ménière’s disease may need referral to an ear, nose and throat specialist for consideration of other drug treatments such as an injection of gentamicin into the middle ear.

What are the implications?

Both steroids and antibiotics appeared to be effective for people with severe Ménière’s disease. Although gentamicin affected inner ear function, this did not translate into serious hearing or balance problems in this small study population.

Specialists should discuss both treatment options with patients, taking into account the permanent damage that could be caused by gentamicin versus the potentially higher number of injections that might be required with steroids. Half of the people in the methylprednisolone group required more than two injections, which may affect patient choice.

Steroid injections would be particularly worth trying for people who are affected in both ears; because gentamicin would not be an option for them because of the small chance it could cause permanent hearing loss.

Citation and Funding

Patel M, Agarwal K, Arshad Q, et al. Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial. Lancet. 2016;388(10061):2753-62.

This project was funded by the Ménière's Society and the National Institute for Health Research Biomedical Research Centre based at Imperial College.

Bibliography

NICE CKS. Meniere's disease. London: National Institute for Health and Care Excellence Clinical Knowledge Summary; 2012.

NHS Choices. Ménière’s disease. London: Department of Health; updated 2015.

Phillips JS, Westerberg B. Intratympanic steroids for Meniere's disease or syndrome. Cochrane Database Syst Rev. 2011;(7):CD008514.

Pullens B, van Benthem PP. Intratympanic gentamicin for Ménière's disease or syndrome. Cochrane Database Syst Rev. 2011;(3):CD008234.

Rauch SD. Ménière's disease: damaged hearing but reduced vertigo. Lancet. 2016;388(10061):2716-17.

Why was this study needed?

Ménière’s disease is an inner ear condition that can cause attacks of dizziness, balance problems (vertigo), nausea and vomiting, ringing in the ears (tinnitus) and hearing loss. An estimated one in 1,000 people in the UK have Ménière's disease.

In most people with Ménière's disease, attacks of vertigo can be reduced with a low salt diet, lifestyle changes and the drug betahistine.

In those who experience severe and frequent attacks of vertigo, injecting gentamicin through the eardrum into the middle ear can help. This benefit is achieved through its toxic effects on the parts of the inner ear involved with balance. Gentamicin injections can also cause attacks of vertigo and hearing loss.

Steroids have also been used to treat Ménière’s disease, because unlike gentamicin, they do not damage inner ear function. However, little evidence is available to compare the effectiveness of these approaches.

What did this study do?

The participants had Ménière's disease in one ear, and severe attacks of vertigo that had not responded to standard treatment.

Two middle ear injections were given, two weeks apart. Participants were assessed for vertigo symptoms, balance and hearing at baseline (0 months) and at one, two, six, 12, 18 and 24 months.

If vertigo returned then additional injections were given: either the same drug or switching to the other drug as chosen by a separate unblinded clinician (the patient and other clinicians remained blinded).  

This study did not have a placebo control group, so it is possible that any reduction in attacks of vertigo could be part of the fluctuating course of Ménière’s disease rather than a true effect of either treatment. The small number of participants means the study was underpowered for some results.

What did it find?

  • The average number of vertigo attacks decreased by 90% in the methylprednisolone group (from 16.4 attacks in the six months before treatment to 1.6 in the final six months of follow-up) and 87% in the gentamicin group (from 19.9 attacks to 2.5). The difference was not statistically significant.
  • Two thirds (67%) of people in the methylprednisolone group and a similar proportion (63%) in the gentamicin group had no attacks of vertigo between 18 and 24 months after treatment.
  • The total number of injections per patient was 2.7 (SD1.7) in the gentamicin group and 3.7 (SD2.5) in the methylprednisolone group.Two patients in the methylprednisolone group were deemed treatment failures and received gentamicin.
  • Both groups also had substantial improvements in tinnitus and dizziness.
  • Though inner ear function tests were worse in people who received gentamicin, there were no differences between the groups on questionnaires about balance.
  • Hearing ability did not change in either group compared to baseline.
  • Three people in each group reported mild adverse events, mostly minor ear infections.

What does current guidance say on this issue?

The NICE 2012 Clinical Knowledge Summary on Ménière’s disease  recommends healthcare professionals should consider prescribing betahistine (initially 16 mg three times a day) to reduce the frequency and severity of attacks of hearing loss, tinnitus and vertigo.

It adds that some people with severe, poorly-controlled Ménière’s disease may need referral to an ear, nose and throat specialist for consideration of other drug treatments such as an injection of gentamicin into the middle ear.

What are the implications?

Both steroids and antibiotics appeared to be effective for people with severe Ménière’s disease. Although gentamicin affected inner ear function, this did not translate into serious hearing or balance problems in this small study population.

Specialists should discuss both treatment options with patients, taking into account the permanent damage that could be caused by gentamicin versus the potentially higher number of injections that might be required with steroids. Half of the people in the methylprednisolone group required more than two injections, which may affect patient choice.

Steroid injections would be particularly worth trying for people who are affected in both ears; because gentamicin would not be an option for them because of the small chance it could cause permanent hearing loss.

Citation and Funding

Patel M, Agarwal K, Arshad Q, et al. Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial. Lancet. 2016;388(10061):2753-62.

This project was funded by the Ménière's Society and the National Institute for Health Research Biomedical Research Centre based at Imperial College.

Bibliography

NICE CKS. Meniere's disease. London: National Institute for Health and Care Excellence Clinical Knowledge Summary; 2012.

NHS Choices. Ménière’s disease. London: Department of Health; updated 2015.

Phillips JS, Westerberg B. Intratympanic steroids for Meniere's disease or syndrome. Cochrane Database Syst Rev. 2011;(7):CD008514.

Pullens B, van Benthem PP. Intratympanic gentamicin for Ménière's disease or syndrome. Cochrane Database Syst Rev. 2011;(3):CD008234.

Rauch SD. Ménière's disease: damaged hearing but reduced vertigo. Lancet. 2016;388(10061):2716-17.

Intratympanic methylprednisolone versus gentamicin in patients with unilateral Meniere's disease: a randomised, double-blind, comparative effectiveness trial

Published on 21 November 2016

Patel, M.,Agarwal, K.,Arshad, Q.,Hariri, M.,Rea, P.,Seemungal, B. M.,Golding, J. F.,Harcourt, J. P.,Bronstein, A. M.

Lancet , 2016

BACKGROUND: Meniere's disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin, the standard treatment for refractory Meniere's disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin. METHODS: In this double-blind comparative effectiveness trial, patients aged 18-70 years with refractory unilateral Meniere's disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone (62.5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18-24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529. FINDINGS: Between June 19, 2009, and April 15, 2013, 256 patients with Meniere's disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the final 6 months compared with the 6 months before the first injection (primary outcome) decreased from 19.9 (SD 16.7) to 2.5 (5.8) in the gentamicin group (87% reduction) and from 16.4 (12.5) to 1.6 (3.4) in the methylprednisolone group (90% reduction; mean difference -0.9, 95% CI -3.4 to 1.6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group. INTERPRETATION: Methylprednisolone injections are a non-ablative, effective treatment for refractory Meniere's disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. FUNDING: Meniere's Society and National Institute for Health Research Imperial Biomedical Research Centre.

Expert commentary

Antibiotics and steroids injected directly into the ear have both been used to control the disabling vertigo attacks that are the main problem for people with Meniere’s disease. This study compared the two drugs by selecting 60 patients and giving half of them gentamicin and half of them methylprednisolone. Neither the doctors nor the patients knew which they had received. After two years both groups had experienced a 90% improvement. This is good news since gentamicin sometimes causes hearing loss and cannot be used in the 50% of patients who develop Ménière’s disease in both ears.

Mr Peter Prinsley, Consultant Ear, Nose & Throat Surgeon, Norfolk & Norwich University Hospital NHS Trust

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