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Otolaryngology

Association of Central Noninvasive Brain Stimulation Interventions With Efficacy and Safety in Tinnitus ManagementA Meta-analysis

Educational Objective
To estimate the association between different central noninvasive brain stimulation interventions and relative efficacy and acceptability in patients with tinnitus.

1 Credit CME

JAMA Otolaryngology–Head & Neck Surgery

September 1, 2020

Original Investigation

Article Information and Disclosures

Jiann-Jy Chen, MD^1,2;

Bing-Syuan Zeng, MD³;

Ching-Nung Wu, MD⁴;

et al

Brendon Stubbs, MD, PhD^5,6,7;

Andre F. Carvalho, MD, PhD^8,9;

Andre R. Brunoni, MD, PhD^10,11;

Kuan-Pin Su, MD, PhD^5,12,13,14;

Yu-Kang Tu, DDS, PhD^15,16;

Yi-Cheng Wu, MD¹⁷;

Tien-Yu Chen, MD^18,19;

Pao-Yen Lin, MD, PhD^20,21;

Chih-Sung Liang, MD^22,23;

Chih-Wei Hsu, MD²⁰;

Shih-Pin Hsu, MD²⁴;

Hung-Chang Kuo, MD²⁴;

Yen-Wen Chen, MD²;

Ping-Tao Tseng, MD²;

Cheng-Ta Li, MD, PhD^25,26,27

Author Affiliations

¹Department of Neurology, E-Da Cancer Hospital, Kaohsiung, Taiwan
²Prospect Clinic for Otorhinolaryngology and Neurology, Kaohsiung City, Taiwan
³Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
⁴Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
⁵Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Department of Psychological Medicine, London, United Kingdom
⁶Physiotherapy Department, South London and Maudsley NHS (National Health Service) Foundation Trust, London, United Kingdom
⁷Positive Ageing Research Institute (PARI), Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, United Kingdom
⁸Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
⁹Centre for Addiction and Mental Health, Toronto, Ontario, Canada
¹⁰Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of Sao Paulo, Sao Paulo, Brazil
¹¹Interdisciplinary Center for Applied Neuromodulation, University Hospital, University of Sao Paulo, Sao Paulo, Brazil
¹²Department of Psychiatry and Mind-Body Interface Laboratory, China Medical University Hospital, Taichung, Taiwan
¹³College of Medicine, China Medical University, Taichung, Taiwan
¹⁴An-Nan Hospital, China Medical University, Tainan, Taiwan
¹⁵Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
¹⁶Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
¹⁷Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan
¹⁸Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
¹⁹Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan
²⁰Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
²¹Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
²²Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
²³Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
²⁴Department of Neurology, E-Da Hospital/School of Medicine, I-Shou University, Kaohsiung, Taiwan
²⁵Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
²⁶Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan
²⁷Institute of Brain Science and Brain Research Center, School of Medicine, National Yang-Ming University, Taipei, Taiwan

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Key Points

Question Which noninvasive brain stimulation treatment was associated with the best efficacy and acceptability in tinnitus management?

Findings In this meta-analysis of 32 unique studies including 1458 unique participants, the cathodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex combined with transcranial random noise stimulation over the bilateral auditory cortex was associated with the greatest improvement in both tinnitus severity and quality of life. Continuous theta-burst stimulation over both auditory cortices ranked more favorably than that over the left auditory cortex only.

Meaning Regarding the efficacy and acceptability for tinnitus treatment, these findings suggest that the cathodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex combined with transcranial random noise stimulation over the bilateral auditory cortex is preferable.

Abstract

Importance Tinnitus has a prevalence of 10% to 25% and is frequently associated with numerous complications, such as neuropsychiatric disease. Traditional treatments have failed to meet the needs of patients with tinnitus. Noninvasive brain stimulation (NIBS) can focally modify cortical functioning and has been proposed as a strategy for reducing tinnitus severity. However, the results have been inconclusive.

Objective To evaluate the association between different central NIBS therapies and efficacy and acceptability for treatment of tinnitus.

Data Sources ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, and Web of Science databases were searched from inception to August 4, 2019. No language restriction was applied. Manual searches were performed for potentially eligible articles selected from the reference lists of review articles and pairwise meta-analyses.

Study Selection Randomized clinical trials (RCTs) examining the central NIBS method used in patients with unilateral or bilateral tinnitus were included in the current network meta-analysis. The central NIBS method was compared with sham, waiting list, or active controls. Studies that were not clinical trials or RCTs and did not report the outcome of interest were excluded.

Data Extraction and Synthesis Two authors independently screened the studies, extracted the relevant information, and evaluated the risk of bias in the included studies. In cases of discrepancy, a third author became involved. If manuscript data were not available, the corresponding authors or coauthors were approached to obtain the original data. This network meta-analysis was based on the frequentist model.

Main Outcomes and Measures The primary outcome was change in the severity of tinnitus. Secondary outcomes were changes in quality of life and the response rate related to the NIBS method in patients with tinnitus.

Results Overall, 32 unique RCTs were included with 1458 unique participants (mean female proportion, 34.4% [range, 0%-81.2%]; mean age, 49.6 [range, 40.0-62.8] years; median age, 49.8 [interquartile range, 48.1-52.4] years). The results of the network meta-analysis revealed that cathodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex combined with transcranial random noise stimulation over the bilateral auditory cortex was associated with the greatest improvement in tinnitus severity (standardized mean difference [SMD], –1.89; 95% CI, –3.00 to –0.78) and quality of life (SMD, –1.24; 95% CI, –2.02 to –0.45) compared with the controls. Improvement in tinnitus severity ranked more favorably for continuous theta-burst stimulation (cTBS) over both auditory cortices (SMD, −0.79; 95% CI = −1.57 to −0.01) than cTBS over only the left auditory cortex (SMD, −0.30; 95% CI, −0.87 to 0.28), compared with controls. Repetitive transcranial magnetic stimulation with priming had a superior beneficial association with tinnitus severity compared with the strategies without priming. None of the investigated NIBS types had a significantly different dropout rate compared with that of the control group.

Conclusions and Relevance This network meta-analysis suggests a potential role of NIBS interventions in tinnitus management. Future large-scale RCTs focusing on longer follow-up and different priming procedure NIBS are warranted to confirm these findings.

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Article Information

Accepted for Publication: May 5, 2020.

Corresponding Authors: Ping-Tao Tseng, MD, Prospect Clinic for Otorhinolaryngology and Neurology, No. 252, Nanzixin Road, Nanzi District, Kaohsiung City 81166, Taiwan (ducktseng@gmail.com), and Cheng-Ta Li, MD, PhD, Division of Community and Rehabilitation Psychiatry, Department of Psychiatry, Taipei Veterans General Hospital, Taiwan, No. 201, Section 2, Shipai Road, Beitou District, Taipei City 11267, Taiwan (on5083@msn.com).

Published Online: July 9, 2020. doi:10.1001/jamaoto.2020.1497

Author Contributions: Drs J.-J. Chen and Zeng contributed equally as co–first authors, Drs Y-W Chen and Tseng had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: J.-J. Chen, Zeng, C.-N. Wu, Su, Tu, T.-Y. Chen, Liang, C.-W. Hsu, S.-P. Hsu, Kuo, Y.-W. Chen, Tseng.

Acquisition, analysis, or interpretation of data: J.-J. Chen, Zeng, Stubbs, Carvalho, Brunoni, Tu, Y.-C. Wu, T.-Y. Chen, Lin, Liang, Tseng, Li.

Drafting of the manuscript: J.-J. Chen, Zeng, Stubbs, Carvalho, Tu.

Critical revision of the manuscript for important intellectual content: C.-N. Wu, Stubbs, Carvalho, Brunoni, Su, Tu, Y.-C. Wu, T.-Y. Chen, Lin, Liang, C.-W. Hsu, S.-P. Hsu, Kuo, Y.-W. Chen, Tseng, Li.

Statistical analysis: J.-J. Chen, Carvalho, Tu, Liang, Y.-W. Chen, Tseng, Li.

Administrative, technical, or material support: J.-J. Chen, Zeng, Stubbs, T.-Y. Chen, Kuo, Tseng, Li.

Supervision: Stubbs, Brunoni, Su, Tu, Y.-C. Wu, Tseng, Li.

Conflict of Interest Disclosures: Dr Brunoni reported receiving academic support in the form of financial fees, outside the submitted work, from the University of Sao Paulo Medical School and the National Council for Scientific and Technological Development, and being a medical adviser for Flow Neuroscience with a small equity of the company (he receives no personal fees from the company). No other disclosures were reported.

Funding/Support: This study was supported by Clinical Lectureship ICA-CL-2017-03-001 jointly funded by Health Education England and the National Institute for Health Research (NIHR) (Dr Stubbs); the NIHR Biomedical Research Centre at South London and Maudsley NHS (National Health Service) Foundation Trust (Dr Stubbs); Maudsley Charity, King’s College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care funding (Dr Stubbs); grants MOST 106-2314-B-039-027-MY3, 107-2314-B-039-005, 108-2320-B-039-048, and 108-2314-B-039-016 from the Ministry of Science and Technology, Taiwan (Dr Su); grants DMR-107-091, DRM-108-091, CRS-108-048, CMU108-SR-106, DMR-108-216, CMRC-CMA-3, and DMR-109-102 from the Chinese Medicine Research Center from the China Medical University, Taiwan (Dr Su); grants MOST 106-2314-B-182A-085-MY2 and MOST 105-2314-B-182A-057 from the Ministry of Science and Technology, Taiwan (Dr Lin); grants CMRPG8F1371 and CMRPG8E1061F from Kaohsiung Chang Gung Memorial Hospital, Taiwan (Dr Lin); grant 106-2314-B-002-098-MY3 from the Ministry of Science and Technology, Taiwan (Dr Tu); grant MOST 108-2321-B-075-004-MY2) from the Ministry of Science and Technology; and grant 108BRC-B502 from the Brain Research Center within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan (National Yang-Ming University from The Featured Areas Research Center Program).

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions.

Additional Contributions: This article was edited by Wallace Academic Editing. The work was not funded by any source of funding.

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Association of Central Noninvasive Brain Stimulation Interventions With Efficacy and Safety in Tinnitus ManagementA Meta-analysis

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