TY - JOUR
T1 - Systemic pharmacological interventions for Ménière's disease
AU - Webster, Katie E.
AU - Galbraith, Kevin
AU - Harrington-Benton, Natasha A.
AU - Judd, Owen
AU - Kaski, Diego
AU - Maarsingh, Otto R.
AU - MacKeith, Samuel
AU - Ray, Jaydip
AU - van Vugt, Vincent A.
AU - Burton, Martin J.
N1 - Funding Information: Quote: "This study was not industry supported. The study was supported by grants from the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung (BMBF), support code 01KG0708; sponsor’s protocol code no 04T-617). This work was supported by the German Centre for Vertigo and Balance Disorders (DSGZ), University Hospital Munich, Campus Grosshadern, Funding Information: This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane ENT, as well as an Evidence Synthesis Programme Grant (NIHR132217). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Evidence Synthesis Programme, NIHR, NHS or the Department of Health. Funding Information: This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane ENT, as well as an Evidence Synthesis Programme Grant (NIHR132217). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Evidence Synthesis Programme, NIHR, NHS or the Department of Health. The development of the protocol (including the prioritisation of outcomes) for this review was informed by responses to a survey to encourage patient and public involvement in the review process. The development and distribution of this survey would not have been possible without the support of the Ménière's Society and the Migraine Trust, and the authors wish to thank them for their help. We would also like to thank the members and affiliates of the Ménière's Society who contributed to discussions about minimally important differences in vertigo outcomes. The authors would like to thank Lee Yee Chong for her work on generic text that has been used and adapted (with permission) in the methods section of the review protocol, and final review. We would also like to extend our thanks to Frances Kellie and Cochrane Pregnancy and Childbirth for their permission to use and reproduce the Cochrane Pregnancy and Childbirth Trustworthiness Screening Tool in this review. The authors are grateful to Professor Malcolm Hilton, Royal Devon University Hospital NHS Trust, for peer review of both the protocol and this review, as well as the others in the Ménière's disease series. We are also grateful to Brian Duncan for his consumer review of this review and the whole Ménière's disease series. Thanks also to Francesca Edwards for her consumer review of the protocol for this review, and to Anne Littlewood, Information Specialist with Cochrane Oral Health, for providing peer review comments on the draft search methods. Many thanks to Dr Richard Rosenfeld for the editorial sign-off of this review and the others in the Ménière's disease series, and to Professor Peter Tugwell for the editorial sign-off of the protocols. We would like to thank Samantha Cox, Ben George and Ambrose Lee, who contributed to the selection of studies for this review. We would also like to thank those who provided help with translation of publication abstracts: Jenny Bellorini, Yuan Chi, Yutaka Hayakawa, Tomohiko Kamo, Magdalena Koperny, Filip Lyng Lindgren, Stefano Morettini, Jungho Park, Stefan Plontke and Roderick Venekamp. We extend our thanks to Christine Adrion who kindly supplied additional data from the BEMED study for inclusion in this review. Finally, our grateful thanks to Jenny Bellorini, Managing Editor for Cochrane ENT, and Samantha Cox, Information Specialist, without whom the development of these reviews would not have been possible. Cochrane ENT supported the authors in the development of this review. The following people conducted the editorial process for this article: Sign-off Editor (final editorial decision): Dr Richard Rosenfeld, Editor Cochrane ENT. Managing Editor (selected peer reviewers, collated peer reviewer comments, provided editorial guidance to authors, edited the article): Jenny Bellorini, Cochrane ENT. Copy Editor (copy editing and production): Jenny Bellorini, Cochrane ENT. Peer reviewers (provided comments and recommended an editorial decision): Professor Malcolm Hilton, Royal Devon University Hospital NHS Trust (clinical/content review), Dr Richard Rosenfeld, Editor Cochrane ENT (clinical/content review), Dr Adrian James, Editor Cochrane ENT (clinical/content review), Brian Duncan (consumer review), Anne Littlewood, Cochrane Oral Health (search review). Sign-off Editor (final editorial decision): Dr Richard Rosenfeld, Editor Cochrane ENT. Managing Editor (selected peer reviewers, collated peer reviewer comments, provided editorial guidance to authors, edited the article): Jenny Bellorini, Cochrane ENT. Copy Editor (copy editing and production): Jenny Bellorini, Cochrane ENT. Peer reviewers (provided comments and recommended an editorial decision): Professor Malcolm Hilton, Royal Devon University Hospital NHS Trust (clinical/content review), Dr Richard Rosenfeld, Editor Cochrane ENT (clinical/content review), Dr Adrian James, Editor Cochrane ENT (clinical/content review), Brian Duncan (consumer review), Anne Littlewood, Cochrane Oral Health (search review). Publisher Copyright: Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.
PY - 2023/2/23
Y1 - 2023/2/23
N2 - BACKGROUND: Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have been used in the management of this condition, including betahistine, diuretics, antiviral medications and corticosteroids. The underlying cause of Ménière's disease is unknown, as is the way in which these treatments may work. The efficacy of these different interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear. OBJECTIVES: To evaluate the benefits and harms of systemic pharmacological interventions versus placebo or no treatment in people with Ménière's disease. SEARCH METHODS: 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. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable Ménière's disease comparing betahistine, diuretics, antihistamines, antivirals or systemic corticosteroids 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). DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: We included 10 studies with a total of 848 participants. The studies evaluated the following interventions: betahistine, diuretics, antivirals and corticosteroids. We did not identify any evidence on antihistamines. Betahistine Seven RCTs (548 participants) addressed this comparison. However, we were unable to conduct any meta-analyses for our primary outcomes as not all outcomes were considered by every study, and studies that did report the same outcome used different time points for follow-up, or assessed the outcome using different methods. Therefore, we were unable to draw meaningful conclusions from the numerical results. Some data were available for each of our primary outcomes, but the evidence was low- or very low-certainty throughout. One study reported on the outcome 'improvement in vertigo' at 6 to ≤ 12 months, and another study reported this outcome at > 12 months. Four studies reported on the change in vertigo, but again all used different methods of assessment (vertigo frequency, or a global score of vertigo severity) or different time points. A single study reported on serious adverse events. Diuretics Two RCTs addressed this comparison. One considered the use of isosorbide (220 participants), and the other used a combination of amiloride hydrochloride and hydrochlorothiazide (80 participants). Again, we were unable to conduct any meta-analyses for our primary outcomes, as only one study reported on the outcome 'improvement in vertigo' (at 6 to ≤ 12 months), one study reported on change in vertigo (at 3 to < 6 months) and neither study assessed serious adverse events. Therefore, we were unable to draw meaningful conclusions from the numerical results. The evidence was all very low-certainty. Other pharmacological interventions We also identified one study that assessed antivirals (24 participants), and one study that assessed corticosteroids (16 participants). The evidence for these interventions was all very low-certainty. Again, serious adverse events were not considered by either study. AUTHORS' CONCLUSIONS: The evidence for systemic pharmacological interventions for Ménière's disease is very uncertain. There are few RCTs that compare these interventions to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. 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-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.
AB - BACKGROUND: Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. A number of pharmacological interventions have been used in the management of this condition, including betahistine, diuretics, antiviral medications and corticosteroids. The underlying cause of Ménière's disease is unknown, as is the way in which these treatments may work. The efficacy of these different interventions at preventing vertigo attacks, and their associated symptoms, is currently unclear. OBJECTIVES: To evaluate the benefits and harms of systemic pharmacological interventions versus placebo or no treatment in people with Ménière's disease. SEARCH METHODS: 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. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable Ménière's disease comparing betahistine, diuretics, antihistamines, antivirals or systemic corticosteroids 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). DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: We included 10 studies with a total of 848 participants. The studies evaluated the following interventions: betahistine, diuretics, antivirals and corticosteroids. We did not identify any evidence on antihistamines. Betahistine Seven RCTs (548 participants) addressed this comparison. However, we were unable to conduct any meta-analyses for our primary outcomes as not all outcomes were considered by every study, and studies that did report the same outcome used different time points for follow-up, or assessed the outcome using different methods. Therefore, we were unable to draw meaningful conclusions from the numerical results. Some data were available for each of our primary outcomes, but the evidence was low- or very low-certainty throughout. One study reported on the outcome 'improvement in vertigo' at 6 to ≤ 12 months, and another study reported this outcome at > 12 months. Four studies reported on the change in vertigo, but again all used different methods of assessment (vertigo frequency, or a global score of vertigo severity) or different time points. A single study reported on serious adverse events. Diuretics Two RCTs addressed this comparison. One considered the use of isosorbide (220 participants), and the other used a combination of amiloride hydrochloride and hydrochlorothiazide (80 participants). Again, we were unable to conduct any meta-analyses for our primary outcomes, as only one study reported on the outcome 'improvement in vertigo' (at 6 to ≤ 12 months), one study reported on change in vertigo (at 3 to < 6 months) and neither study assessed serious adverse events. Therefore, we were unable to draw meaningful conclusions from the numerical results. The evidence was all very low-certainty. Other pharmacological interventions We also identified one study that assessed antivirals (24 participants), and one study that assessed corticosteroids (16 participants). The evidence for these interventions was all very low-certainty. Again, serious adverse events were not considered by either study. AUTHORS' CONCLUSIONS: The evidence for systemic pharmacological interventions for Ménière's disease is very uncertain. There are few RCTs that compare these interventions to placebo or no treatment, and the evidence that is currently available from these studies is of low or very low certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. 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-analyses of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits.
KW - Adrenal Cortex Hormones
KW - Adult
KW - Betahistine
KW - Diuretics
KW - Histamine Antagonists
KW - Humans
KW - Meniere Disease/therapy
KW - Tinnitus
KW - Vertigo
UR - http://www.scopus.com/inward/record.url?scp=85148964316&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/14651858.CD015171.pub2
DO - https://doi.org/10.1002/14651858.CD015171.pub2
M3 - Article
C2 - 36827524
SN - 1469-493X
VL - 2023
SP - CD015171
JO - Cochrane Database of Systematic Reviews
JF - Cochrane Database of Systematic Reviews
IS - 2
M1 - CD015171
ER -