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Review
. 2018 Dec 28;12(12):CD013093.
doi: 10.1002/14651858.CD013093.pub2.

Betahistine for tinnitus

Inge Wegner  1 , Deborah A Hall, Adriana Leni Smit, Don McFerran, Inge Stegeman
Affiliations
Review

Betahistine for tinnitus

Inge Wegner et al. Cochrane Database Syst Rev. .

Abstract

Background: Tinnitus is a symptom defined as the perception of sound in the absence of an external source. In England alone there are an estimated ¾ million general practice consultations every year where the primary complaint is tinnitus, equating to a major burden on healthcare services. Clinical management strategies include education and advice, relaxation therapy, tinnitus retraining therapy, cognitive behavioural therapy, sound enrichment using ear-level sound generators or hearing aids, and drug therapies to manage co-morbid symptoms such as sleep difficulties, anxiety or depression. As yet, no drug has been approved for tinnitus by a regulatory body. Nonetheless, over 100,000 prescriptions for betahistine are being filled every month in England, and nearly 10% of general practitioners prescribe betahistine for tinnitus.

Objectives: To assess the effects of betahistine in patients with subjective idiopathic tinnitus.

Search methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL, via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 July 2018.

Selection criteria: Randomised controlled trials (RCTs) recruiting patients of any age with acute or chronic subjective idiopathic tinnitus were included. We included studies where the intervention involved betahistine and this was compared to placebo, no intervention or education and information. We included all courses of betahistine, regardless of dose regimens or formulations and for any duration of treatment.

Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes included tinnitus loudness and significant adverse effects (upper gastrointestinal discomfort). Our secondary outcomes included tinnitus symptom severity as measured by the global score on a multi-item tinnitus questionnaire, depressive symptoms, symptoms of generalised anxiety, health-related quality of life, other adverse effects (e.g. headache, drowsiness, allergic skin reactions (pruritis, rashes) and exacerbation of tinnitus) and tinnitus intrusiveness. We used GRADE to assess the quality of evidence for each outcome; this is indicated in italics.

Main results: This review included five studies (with a total of 303 to 305 participants) comparing the effects of betahistine with placebo in adults with subjective idiopathic tinnitus. Four studies were parallel-group RCTs and one had a cross-over design. The risk of bias was unclear in all of the included studies.Due to heterogeneity in the outcomes measured and measurement methods used, very limited data pooling was possible. When we pooled the data from two studies for the primary outcome tinnitus loudness, the mean difference on a 0- to 10-point visual analogue scale at one-month follow-up was not significant between betahistine and placebo (-0.16, 95% confidence interval (CI) -1.01 to 0.70; 81 participants) (very low-quality evidence). There were no reports of upper gastrointestinal discomfort (significant adverse effect) in any study.As a secondary outcome, one study found no difference in the change in the Tinnitus Severity Index between betahistine and placebo (mean difference at 12 weeks 0.02, 95% CI -1.05 to 1.09; 50 participants) (moderate-quality evidence). None of the studies reported the other secondary outcomes of changes in depressive symptoms or depression, anxiety symptoms or generalised anxiety, or health-related quality of life as measured by a validated instrument, nor tinnitus intrusiveness.Other adverse effects that were reported were not treatment-related.

Authors' conclusions: There is an absence of evidence to suggest that betahistine has an effect on subjective idiopathic tinnitus when compared to placebo. The evidence suggests that betahistine is generally well tolerated with a similar risk of adverse effects to placebo treatments. The quality of evidence for the reported outcomes, using GRADE, ranged from moderate to very low.If future research into the effectiveness of betahistine in patients with tinnitus is felt to be warranted, it should use rigorous methodology. Randomisation and blinding should be of the highest quality, given the subjective nature of tinnitus and the strong likelihood of a placebo response. The CONSORT statement should be used in the design and reporting of future studies. We also recommend the development of validated, patient-centred outcome measures for research in the field of tinnitus.

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Conflict of interest statement

Deborah A Hall: is an NIHR Senior Investigator and Section Editor for the journal Hearing Research, Elsevier. She leads the Core Outcome Measures in Tinnitus (COMiT) initiative whose work is currently supported by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 764604 and the NIHR Nottingham Biomedical Research Centre.

Inge Wegner: none known.

Adriana L Smit: none known.

Don McFerran: receives royalties for writing books on tinnitus has received consultancy honoraria from GlaxoSmithKline, Autifony and Otonomy.

Inge Stegeman: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 1 Tinnitus loudness VAS (1 month).
1.2
1.2. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 2 Tinnitus loudness VAS (2 months).
1.3
1.3. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 3 Change in tinnitus loudness VAS (short‐term).
1.4
1.4. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 4 Significant adverse effects (short‐term).
1.5
1.5. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 5 Significant adverse effects (long‐term).
1.6
1.6. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 6 Change in Tinnitus Severity Index (long‐term).
1.7
1.7. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 7 Tinnitus severity score (long‐term).
1.8
1.8. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 8 Other adverse effects (short‐term).
1.9
1.9. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 9 Other adverse effects (long‐term).
1.10
1.10. Analysis
Comparison 1 Betahistine versus placebo (without concurrent medication), Outcome 10 Change in tinnitus severity score (long‐term).
2.1
2.1. Analysis
Comparison 2 Betahistine versus placebo (with concurrent medication), Outcome 1 Change in tinnitus loudness match (short‐term).
2.2
2.2. Analysis
Comparison 2 Betahistine versus placebo (with concurrent medication), Outcome 2 Significant adverse effects (short‐term).
2.3
2.3. Analysis
Comparison 2 Betahistine versus placebo (with concurrent medication), Outcome 3 Other adverse effects (short‐term).
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013093

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