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. 2021 Aug 9;13:730758. doi: 10.3389/fnagi.2021.730758

Corrigendum: Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers

Jorge Piano Simoes 1,*,, Elza Daoud 2,*,, Maryam Shabbir 3,*,, Sana Amanat 4, Kelly Assouly 5,6,7, Roshni Biswas 3,8, Chiara Casolani 9,10,11, Albi Dode 12, Falco Enzler 2, Laure Jacquemin 13,14, Mie Joergensen 9,15, Tori Kok 16, Nuwan Liyanage 17,18, Matheus Lourenco 19,20, Punitkumar Makani 21,22, Muntazir Mehdi 23, Anissa L Ramadhani 24,25, Constanze Riha 26, Jose Lopez Santacruz 21,22, Axel Schiller 1, Stefan Schoisswohl 1, Natalia Trpchevska 27, Eleni Genitsaridi 3,28,*,
PMCID: PMC8381868  PMID: 34434102

In the original article, there was an error. For the sentence “NMDA receptor antagonists (AM-101) have been discontinued in phase III for not meeting endpoints (van de Heyning et al., 2014)” there was a typographical error (phase III should have been phase II). In addition, it was brought to our attention that clinical trials for AM-101 are ongoing.

A correction has been made to section 6. Treatment Development, Subsection 6.4. Pharmacology-Based Interventions, paragraph 1. The corrected paragraph is below.

A wide variety of therapeutic drugs have been used to relieve tinnitus (Elgoyhen and Langguth, 2010). For acute tinnitus, a dose-dependent reduction in tinnitus intensity was observed with intravenous lidocaine (Trellakis et al., 2006). However, its use is controversial due to its short-lasting response, its potentially life threatening arrhythmogenic side effects, and the low bioavailability of its oral form (Israel et al., 1982; Trellakis et al., 2007; Gil-Gouveia and Goadsby, 2009). A potential goal of pharmacologic tinnitus research could be to identify the mechanism by which lidocaine interferes with tinnitus and mimic this effect using a drug with better tolerance that can be orally administered. For chronic tinnitus, the off-label use of medicines like betahistine (Hall et al., 2018d), anticonvulsants (Hoekstra et al., 2011), and glutamate receptor antagonists have shown little or no effect in clinical trials. Prescription of antidepressants and benzodiazepines is limited to tinnitus-associated comorbidities such as depression, insomnia and anxiety (Langguth et al., 2019). Moreover, three clinical research programs, in the last few years, were discontinued in phase II and III. AMPA antagonist selurampanel (BGG492) has not resulted in a new compound (Cederroth et al., 2018). NMDA receptor antagonists (AM-101) did not meet the primary endpoint of improving minimum masking level in acute tinnitus in a phase II clinical trial but showed improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media (van de Heyning et al., 2014). Many other treatments decreasing tinnitus percept or targeting central auditory processing pathways are at a preclinical phase (Schilder et al., 2019). The modulator of voltage-gated potassium channels (Kv3.1) (AUT00063) was not effective in alleviating tinnitus symptoms (Hall et al., 2019b).

The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

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References

  1. Cederroth C. R., Dyhrfjeld-Johnsen J., Langguth B. (2018). An update: emerging drugs for tinnitus. Expert Opin. Emerg. Drugs 23, 251?260. 10.1080/14728214.2018.1555240 [DOI] [PubMed] [Google Scholar]
  2. Elgoyhen A. B., Langguth B. (2010). Pharmacological approaches to the treatment of tinnitus. Drug Discov. Today 15, 300?305. 10.1016/j.drudis.2009.11.003 [DOI] [PubMed] [Google Scholar]
  3. Gil-Gouveia R., Goadsby P. (2009). Neuropsychiatric side-effects of lidocaine: examples from the treatment of headache and a review. Cephalalgia 29, 496?508. 10.1111/j.1468-2982.2008.01800.x [DOI] [PubMed] [Google Scholar]
  4. Hall D. A., Ray J., Watson J., Sharman A., Hutchison J., Harris P., et al. (2019b). A balanced randomised placebo controlled blinded phase iia multi-centre study to investigate the efficacy and safety of aut00063 versus placebo in subjective tinnitus: the quiet-1 trial. Hear. Res. 377, 153?166. 10.1016/j.heares.2019.03.018 [DOI] [PubMed] [Google Scholar]
  5. Hall D. A., Wegner I., Smit A. L., McFerran D., Stegeman I. (2018d). Betahistine for tinnitus. Cochrane Database Syst. Rev. 2018:CD013093. 10.1002/14651858.CD013093.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hoekstra C. E., Rynja S. P., van Zanten G. A., Rovers M. M. (2011). Anticonvulsants for tinnitus. Cochrane Database Syst. Rev. 7:CD007960. 10.1002/14651858.CD007960.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Israel J. M., Connelly J. S., McTigue S. T., Brummett R. E., Brown J. (1982). Lidocaine in the treatment of tinnitus aurium: a double-blind study. Arch. Otolaryngol. 108, 471–473. [DOI] [PubMed] [Google Scholar]
  8. Langguth B., Elgoyhen A. B., Cederroth C. R. (2019). Therapeutic approaches to the treatment of tinnitus. Annu. Rev. Pharmacol. Toxicol. 59, 291?313. 10.1146/annurev-pharmtox-010818-021556 [DOI] [PubMed] [Google Scholar]
  9. Schilder A. G., Su M. P., Blackshaw H., Lustig L., Staecker H., Lenarz T., et al. (2019). Hearing protection, restoration, and regeneration: an overview of emerging therapeutics for inner ear and central hearing disorders. Otol. Neurotol. 40, 559?570. 10.1097/MAO.0000000000002194 [DOI] [PubMed] [Google Scholar]
  10. Trellakis S., Benzenberg D., Urban B. W., Friederich P. (2006). Differential lidocaine sensitivity of human voltage-gated potassium channels relevant to the auditory system. Otol. Neurotol. 27, 117?123. 10.1097/01.mao.0000186443.11832.8a [DOI] [PubMed] [Google Scholar]
  11. Trellakis S., Lautermann J., Lehnerdt G. (2007). Lidocaine: neurobiological targets and effects on the auditory system. Prog. Brain Res. 166, 303?322. 10.1016/S0079-6123(07)66028-2 [DOI] [PubMed] [Google Scholar]
  12. van de Heyning P., Muehlmeier G., Cox T., Lisowska G., Maier H., Morawski K., et al. (2014). Efficacy and safety of am-101 in the treatment of acute inner ear tinnitus a double-blind, randomized, placebo-controlled phase II study. Otol. Neurotol. 35:589. 10.1097/MAO.0000000000000268 [DOI] [PMC free article] [PubMed] [Google Scholar]

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