Current Pharmacological Treatment of Tinnitus : Matrix Science Pharma

Secondary Logo

Journal Logo

Review Article

Current Pharmacological Treatment of Tinnitus

Swain, Santosh Kumar; Dubey, Debasmita1

Author Information
Matrix Science Pharma 6(3):p 53-57, Jul–Sep 2022. | DOI: 10.4103/mtsp.mtsp_11_22
  • Open


Tinnitus is the phantom perception of sound. The pathophysiology of tinnitus is poorly understood in medicine. It is a highly prevalent disorder and treatment is still elusive. Tinnitus is a common otologic symptom presented by patients in the outpatient department of otolaryngology. In some people, tinnitus is a fairly minor irritation but for many, it intrudes to such a degree that it affects their ability to lead a normal life. Individuals who suffer from disabling tinnitus often need medical treatment from an otologist, neurologist, or psychiatrist with the hope of finding a medication that can completely switch off their tinnitus and bring back silence. The available treatment for tinnitus patients is diverse. These include counseling, cognitive behavioral therapies, tinnitus retraining therapy, and input to the auditory system such as hearing aids and cochlear implants. The pharmacological treatment for tinnitus patients is often less discussed in the literature. The search for effective tinnitus treatment faces considerable challenges. Tinnitus is only a symptom that might be the result of different underlying pathologies. Thus, heterogeneity within tinnitus patients is expected and the drug discovery endeavor faces a “one drug will not fit all” scenario. Tinnitus today is still clinically challenging and most patients want a drug that could reduce or even abolish their phantom sound. The objective of this review article is to discuss the current pharmacological treatment of tinnitus.


Tinnitus is derived from the Latin word tinnire and refers to a condition where patient experiences a ringing, buzzing, or hissing auditory sensation in the absence of an external sound.[1] Although many advances have been made in the medical sciences, tinnitus is still thought of as a scientific and clinical enigma for a clinician.[2] Tinnitus is broadly classified into subjective or objective. The objective type of tinnitus is rare and refers to a condition where a real sound is generated by internal biological activity, such as vascular turbulence or pulsations or spasm of the muscle in the middle ear, Eustachian tube, or soft palate.[3] Subjective tinnitus is the most common type and it refers to a phantom auditory sensation for which no objective sound can be identified.[4] The treatment goals for tinnitus patients are aimed at symptomatic relief and its associated distress. There are no standard protocols for treatment of the tinnitus.[5] Drug therapy is one of the treatment approaches for tinnitus. The literature related to pharmacotherapy for tinnitus is vast. Here, this review article will only focus on some of the recent pharmacotherapeutic treatments employed for tinnitus. Despite considerable developments in the understanding of tinnitus, its pharmacological treatment has little progress. The objective of this review article is to discuss the current pharmacological treatment of tinnitus.


Multiple systematic methods were used to find current research publications on the current pharmacological treatment of tinnitus. We started by searching the Scopus, PubMed, MEDLINE, and Google Scholar databases online. A search strategy using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was developed. This search strategy recognized the abstracts of published articles, whereas other research articles were discovered manually from the citations. Randomized controlled studies, observational studies, comparative studies, case series, and case reports were evaluated for eligibility. There were a total number of articles 68 (21 case reports, 24 cases series, and 23 original articles) [Figure 1]. This article focuses only on the current pharmacological treatment of tinnitus. This review article describes the epidemiology and different pharmacological treatment options for patients with tinnitus. This review article provides a better understanding of the pharmacological treatment of disabling tinnitus. It will also serve as a catalyst for additional study into a newer pharmacological agent for the treatment of tinnitus.

Figure 1:
Flowchart showing methods of literature search


Tinnitus is one of the most common hearing disturbances, affecting approximately 17% of the population and approximately 33% of the elderly.[6] The prevalence of tinnitus increases with the degree of age-related hearing impairment.[7] Chronic tinnitus is more prevalent among elderly persons (12% after the age of 60 years) than in young adults (5% of the 20–30 years of age) but can occur in any age group.[7] However, many patients with hearing loss do not present tinnitus, and some individuals with normal hearing present tinnitus. More than 4 million prescriptions are written every year for tinnitus relief in Europe and USA, but these are all off-label prescriptions of a wide variety of drugs.[8]


There is no effective treatment available for management of the tinnitus, although much research work is underway into the pathophysiology and treatment of tinnitus.[9] There is no specific pharmacological agent which has been established for the treatment of tinnitus.[10] There are a large variety of drugs [Table 1] approved for the treatment of tinnitus in clinical practice. There is a fully satisfactory drug still remains elusive. There are different pharmacotherapies available for patients with tinnitus such as lidocaine, vasodilators, benzodiazepines, spasmodic drugs, tricyclic antidepressants, and Ginkgobiloba.[11]

Table 1:
Pharmacological agents used in the treatment of tinnitus


Lidocaine is often used as a local anesthetic agent or to treat cardiac arrhythmias. It is thought to bind to fast voltage-gated sodium channels, reducing the magnitude of sodium current at the time of depolarization.[12] However, the mechanism of action of lidocaine is more complex, as it is known to affect calcium-, potassium-, and glycine-induced chloride currents at micromolar concentrations.[13] Although intravenous lidocaine is thought to be effective in tinnitus, the effect is transient and the route of administration is not practical in a clinical setting of a chronic condition. The location of action of intravenous lidocaine is not properly understood, but there is evidence that it affects both the cochlea and the central nervous system (CNS).[14] In one study with human brain imaging where lidocaine either increased or decreased the loudness of tinnitus, the changes in loudness were associated with altered neural activity in the right auditory cortex.[15] Tocainide is an analog of lidocaine that can be taken orally and was assessed as a potential long-term therapy for tinnitus. Tocainide has little benefit for tinnitus.[15] Intravenous lidocaine has been used to ameliorate tinnitus, but in general, its effect has been limited. The longer-acting local anesthetic agent such as ropivacaine may be more effective to relieve tinnitus.[16]

Glutamate receptor antagonist

Glutamate receptor antagonists have been tried the patients with tinnitus. The rationale behind their use is that imbalance between the inhibitory and excitatory neurotransmission is found in several parts of the auditory pathway.[17] Blockage of the glutamatergic neurotransmission could exert neuroprotectant effects as it is known that noise exposure is followed by an excitotoxic injury of the hair cells. Hence, the administration of glutamate antagonists might prevent labyrinthine damage and, possibly, tinnitus development in the acute phase.[18]


Antidepressants are usually used for the treatment of tinnitus. The cause for the use of such antidepressants can be found in well-documented comorbidity between depressive disorders and tinnitus.[19] Tricyclic groups of drugs are mainly used for tinnitus due to their analgesic effects.[20] This nature of tricyclic antidepressants could be interesting in view of proposed etiological similarities between neuropathic pain and tinnitus. Among the tricyclic antidepressants (trimipramine, amitriptyline, and nortriptyline), nortriptyline is worth mentioning. One study showed that in subjects with severe tinnitus and severe depression or depressive symptoms, nortriptyline significantly decreased the depression scores, tinnitus disability scores, and tinnitus loudness in comparison to placebo.[21] Antidepressants such as serotonin uptake inhibitors such as paroxetine and sertraline are tested for tinnitus. In one randomized double-blind placebo-control study in patients without severe hearing loss but at high risk for developing severe tinnitus, sertraline was more effective than placebo in decreasing tinnitus loudness and severity of tinnitus.[22]


Severe tinnitus is often a stressful situation and heavily affects every aspect of a patient's life. Anxiolytics like benzodiazepines have been used to help patients cope with their tinnitus. In one study, alprazolam decreased tinnitus loudness in 76% of patients, measured with a tinnitus synthesizer and a visual analog scale, whereas only 5% showed a reduction in tinnitus loudness in the control group.[23] In a prospective, randomized, single-blind clinical trial taking 10 patients per group, clonazepam significantly reduced tinnitus loudness and annoyance (visual analog scale) relative to the control group.[24]


Zinc is a trace element, which is seen in minute quantities in living cells but plays a vital role in the metabolism of the body. Zinc is helpful for the proper functioning of the immune system. Zinc is also protective against reactive oxygen species.[25] Zinc appears to be essential for neurogenesis, neuronal migration, and synaptogenesis, and its deficiency is thought to interfere with neurotransmission and, in turn, neuropsychologic behavior.[26] Zinc is widely distributed in the CNS. It acts as a synaptic modulator and plays a role in neuronal death in certain pathogenic conditions. Zinc is also found in the synapse of the auditory system.[27] A study showed that patients with tinnitus may have low blood zinc levels and clinical improvement can be achieved by oral zinc medication.[28]


Acamprosate blocks excitatory glutamatergic N-methyl-d-aspartate (NMDA) receptors, whereas enhancing gamma-aminobutyric acid (GABA)-mediated nerve inhibition.[29] The rationale behind the treatment of tinnitus arises from excess glutamatergic activity through NMDA receptors and/or hyperactivity resulting from the loss of GABA-medicated inhibition.[30]


Caroverine is used as a spasmolytic drug and acts as an antagonist of calcium and non-NMDA and NMDA glutamate receptors.[30] Due to limited uptake with oral administration, caroverine is given intravenously or locally. It has been thought that cochlear synaptic tinnitus is from a synaptic disturbance of NMDA or non-NMDA on the afferent dendrites of the spiral ganglion neurons.[31]


Melatonin is a naturally occurring circulating hormone secreted in the pineal gland and other tissues, binds to the melatonin receptors, and plays a vital role in regulating circadian rhythms.[32] It is also a potent antioxidant that protects mitochondrial and nuclear DNA and has been found to protect against noise- and drug-induced hearing impairment.[32] As sleep disturbances are an important complaint and complicating factor in tinnitus, melatonin was evaluated for the treatment of tinnitus. A recent study showed that melatonin reduced the subjective ratings of tinnitus and tinnitus loudness more than placebo; these improvements were larger if melatonin was combined with the antipsychotic sulpiride, a selective dopamine D2 antagonist.[33]


Memantine is presently used for the treatment of Alzheimer's disease and has shown positive effects in managing depression.[34] It also acts as a voltage-dependent antagonist of NMDA receptors and decreases excitotoxicity by preventing the prolonged influx of calcium.[34] Excitotoxicity mediated by NMDA receptors has been proposed as a mechanism for cochlear tinnitus. High doses of salicylate, the active ingredient in aspirin, reliably enhance tinnitus and augment current through NMDA receptors on cochlear spiral ganglion neurons. NMDA antagonists applied locally to the inner ear blocked behavioral evidence of salicylate-induced tinnitus.[35]


This drug is similar to memantine and is being used for Alzheimer's disease, drug dependence, depression, and pain. Like memantine, neramexane acts as a noncompetitive, voltage-dependent NMDA antagonist. It also blocks α9 and α10 nicotinic cholinergic receptors which are expressed on inner hair cells and α10 nicotinic receptors which are expressed on the inner hair cells in the labyrinth.[36] It is helpful for the treatment of tinnitus.


There are several vasoactive drugs investigated that increase the blood flow which causes increased oxygenation of peripheral and central auditory structures that reduce tinnitus as a consequence.[37] The L-type Ca2+ channel antagonist nimodipine is effective for relieving tinnitus, especially in quinine-induced tinnitus in rates.[38] Vasodilatory properties of histamine were studied for the treatment of tinnitus. Betahistine is one of the commonly prescribed treatments for tinnitus, but its effectiveness is mostly limited to the tinnitus associated with Meniere's disease. Prostaglandins have also properties of vasodilation and are found in both the cochlea and CNS. It has been documented that reduction in prostaglandin metabolism is associated with a response to noise exposure, nonsteroidal anti-inflammatory drugs, aminoglycosides, and loop diuretics; all of which have been reported to be tinnitogenic.[39]

Ginkgo biloba

The extracts derived from the Chinese tree G. biloba yield extract of Ginkgo biloba 761(EGb-761), the active component, which contains flavonoids, terpenes, and vasoactive compounds. G. biloba extract has been used to treat a wide range of disorders including tinnitus due to its vasodilating and antioxidant properties.[40] Studies showed that Ginkgo alleviates tinnitus symptoms, specifically in patients with short-duration symptom.[41] One behavioral study reported with rats taking EGb-761 reduced the behavioral manifestations of salicylate-induced tinnitus.[40] However, the study showed that Ginkgo is no more effective in alleviating tinnitus symptoms than a placebo.[42] Preparations of G. biloba are not standardized and so it is difficult to compare and evaluate the results from different studies, but placebo-controlled trials have so far failed to reveal any particular efficacy, even when combined with various therapies used for tinnitus.[42]

Osmotic regulators

Several conditions are associated with tinnitus as a result of an imbalance in ion distribution and fluid compartmentalization in the cochlea and vestibular apparatus as in Meniere's syndrome.[43] These ion imbalances can cause an increase in the pressure perilymph (perilymphatic hypertension) and result in dysfunction in the cochlea. There are several diuretics have been studied in an attempt to rectify these imbalances and restore normal fluid pressure. The loop diuretic furosemide was documented to be effective in cases of tinnitus that were deemed to be cochlear in origin.

Botulinum toxin

The use of botulinum toxin Type A (BTXA) is used to treat tinnitus due to stapedius myoclonus. Local application of botulinum toxin is helpful in relive tinnitus due to stapedius myoclonus. A piece of gel foam containing BTXA (25 U/ml) is usually placed through a perforation I tympanic membrane, into the middle-ear cavity of a patient presenting with tinnitus due to stapedius myoclonus.[44]

Hyperbaric oxygen therapy

Hyperbaric oxygen therapy involves breathing pure oxygen in a specially designed chamber. It permits a controlled increase of partial oxygen pressure in the blood. This technique can be utilized in patients with tinnitus and sudden deafness when the development in the inner ear and the brain lead to a lack of oxygen and so to a limited energy provision.[45] Hyperbaric oxygen therapy is thought to be beneficial in patients with tinnitus by enhancing oxygen supply to the inner ear and improving tinnitus.[45]


Neurokinin receptors are found in the labyrinth, which has a potential treatment target for relieving tinnitus.[46] Vestipitant is a blocker of the neurokinin-1 receptor, which often binds the substance P.[46] Vestipitant and the combination of paroxetine and vestipitant are currently under clinical trials for the treatment of tinnitus. Transdermal lidocaine acts as a vector for delivering low-dose lidocaine to treat tinnitus. This has been developed for the delivery of lidocaine (LidoPAIN TV, EpiCept) applied over the preauricular skin. Its clinical efficacy is also under clinical trial.


Tinnitus is an extremely prevalent clinical condition that impinges on the lives of sufferers to varying degrees. Tinnitus is a distressing symptom that is characterized by a perceived sensation of sound without a corresponding external stimulus. Although a diverse array of pharmacological agents have been tried, only a few are routinely prescribed by clinicians. There is a pressing need for a drug or a combination of drugs to relieve tinnitus. Antidepressants and anxiolytics are commonly used in pharmacological protocols for the treatment of tinnitus. Most patients and clinicians are waiting for drugs that can relieve tinnitus significantly.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1. Møller AR. Tinnitus: Presence and future Prog Brain Res. 2007;166:3–16
2. Swain SK. Impact of tinnitus on quality of life: A review Int J Adv Med. 2021;8:1006–10
3. Swain SK. Middle ear myoclonus BLDE Univ J Health Sci. 2022;7:179–83
4. Swain SK, Baliarsingh P. Self-reported tinnitus in pediatric age group: Our experiences at a tertiary care teaching hospital in Eastern India Int J Contemp Pediatr. 2022;9:884–8
5. Swain SK. Tinnitus: A morbid clinical entity in COVID-19 patient BLDE Univ J Health Sci. 2022;7:14–8
6. Jastreboff P, Gray WC, Mattox DECummings CW. Tinnitus and hyperacusis Otolaryngology Head Neck Surgery. 19983rd St. Louis Mosby-Year Book
7. Ahmad N, Seidman M. Tinnitus in the older adult: Epidemiology, pathophysiology and treatment options Drugs Aging. 2004;21:297–305
8. Vio MM, Holme RH. Hearing loss and tinnitus: 250 million people and a US$10 billion potential market Drug Discov Today. 2005;10:1263–5
9. Swain SK. Hearing loss, tinnitus and vertigo among pediatric patients with COVID-19 infections: A review Int J Contemp Pediatr. 2021;8:1756–61
10. Swain SK. Cochlear implant and tinnitus: A review Int J Otorhinolaryngol Head Neck Surg. 2021;7:1960–4
11. Swain SK, Nayak S, Ravan JR, Sahu MC. Tinnitus and its current treatment – Still an enigma in medicine J Formos Med Assoc. 2016;115:139–44
12. Lenkowski PW, Shah BS, Dinn AE, Lee K, Patel MK. Lidocaine block of neonatal Nav1.3 is differentially modulated by co-expression of beta1 and beta3 subunits Eur J Pharmacol. 2003;467:23–30
13. Yu M, Chen L. Modulation of major voltage and ligand gated ion channels in cultured neurons of the rat inferior colliculus by lidocaine 1 Acta pharmacol Sin. 2008;29:1409–18
14. Baguley DM, Jones S, Wilkins I, Axon PR, Moffat DA. The inhibitory effect of intravenous lidocaine infusion on tinnitus after translabyrinthine removal of vestibular schwannoma: A double-blind, placebo-controlled, crossover study Otol Neurotol. 2005;26:169–76
15. Reyes SA, Salvi RJ, Burkard RF, Coad ML, Wack DS, Galantowicz PJ, et al Brainimaging of the effects of lidocaine on tinnitus Hear Res. 2002;171:43–50
16. Kallio H, Niskanen ML, Havia M, Neuvonen PJ, Rosenberg PH, Kentala E. I.V. ropivacaine compared with lidocaine for the treatment of tinnitus Br J Anaesth. 2008;101:261–5
17. Eggermont JJ, Roberts LE. The neuroscience of tinnitus Trends Neurosci. 2004;27:676–82
18. Guitton MJ, Wang J, Puel JL. New pharmacological strategies to restore hearing and treat tinnitus Acta Otolaryngol. 2004;124:411–5
19. Belli S, Belli H, Bahcebasi T, Ozcetin A, Alpay E, Ertem U. Assessment of psychopathological aspects and psychiatric comorbidities in patients affected by tinnitus Eur Arch Otorhinolaryngol. 2008;265:279–85
20. Hajhashemi V, Amin B. Effect of glibenclamide on antinociceptive effects of antidepressants of different classes Clinics (Sao Paulo). 2011;66:321–5
21. Sullivan M, Katon W, Russo J, Dobie R, Sakai C. A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms Arch Intern Med. 1993;153:2251–9
22. Zöger S, Svedlund J, Holgers KM. The effects of sertraline on severe tinnitus suffering – A randomized, double-blind, placebo-controlled study J Clin Psychopharmacol. 2006;26:32–9
23. Johnson RM, Brummett R, Schleuning A. Use of alprazolam for relief of tinnitus. A double-blind study Arch Otolaryngol Head Neck Surg. 1993;119:842–5
24. Bahmad FM Jr., Venosa AR, Oliveira CA. Benzodiazepines and GABAergics in treating severe disabling tinnitus of predominantly cochlear origin Int Tinnitus J. 2006;12:140–4
25. Speich M, Pineau A, Ballereau F. Minerals, trace elements and related biologic variables in athletes and during physical activity Clin Chim Acta. 2001;312:1–11
26. Bhatnagar S, Taneja S. Zinc and cognitive development Br J Nutr. 2001;85(Suppl 2):S139–45
27. Zirpel L, Parks TN. Zinc inhibition of group 1 mGluR-mediated calcium homeostasis in auditory neurons J Assoc Res Otolaryngol. 2001;2:180–7
28. Arda HN, Tuncel U, Akdogan O, Ozluoglu LN. The role of zinc in the treatment of tinnitus Otol Neurotol. 2003;24:86–9
29. Pierrefiche O, Daoust M, Naassila M. Biphasic effect of acamprosate on NMDA but not onGABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratorynetwork Neuropharmacology. 2004;47:35–45
30. Brozoski TJ, Spires TJ, Bauer CA. Vigabatrin, a GABA transaminase inhibitor, reversibly eliminates tinnitus in an animal model J Assoc Res Otolaryngol. 2007;8:105–18
31. Guitton MJ, Dudai Y. Blockade of cochlear NMDA receptors prevents long-term tinnitus during abrief consolidation window after acoustic trauma Neural Plast. 2007;2007:1–11
32. Bas E, Martinez-Soriano F, Láinez JM, Marco J. An experimental comparative study of dexamethasone, melatonin and tacrolimus in noise-induced hearing loss Acta Otolaryngol. 2009;129:385–9
33. Lopez-Gonzalez MA, Santiago AM, Esteban-Ortega F. Sulpiride and melatonin decrease tinnitus perception modulating the auditolimbic dopaminergic pathway J Otolaryngol. 2007;36:213–9
34. Rogawski MA, Wenk GL. The neuropharmacological basis for the use of memantine in thetreatment of Alzheimer's disease CNS Drug Rev. 2003;9:275–308
35. Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL. Salicylate induces tinnitus through activation of cochlear NMDA receptors J Neurosci. 2003;23:3944–52
36. Gilling K, Jatzke C, Wollenburg C, Vanejevs M, Kauss V, Jirgensons A, et al A novel class of amino-alkylcyclohexanes as uncompetitive, fast, voltage-dependent, N-methyl-D-aspartate (NMDA) receptor antagonists – In vitro characterization J Neural Transm (Vienna). 2007;114:1529–37
37. Swain SK, Pati BK, Mohanty JN. Otological manifestations in pregnant women – A study at a tertiary care hospital of eastern India J Otol. 2020;15:103–6
38. Jastreboff PJ, Brennan JF, Sasaki CT. Quinine-induced tinnitus in rats Arch Otolaryngol Head Neck Surg. 1991;117:1162–6
39. Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine Otolaryngol Clin North Am. 1993;26:791–810
40. Jastreboff PJ, Zhou S, Jastreboff MM, Kwapisz U, Gryczynska U. Attenuation of salicylate-induced tinnitus by Ginkgo biloba extract in rats Audiol Neurootol. 1997;2:197–212
41. Morgenstern C, Biermann E. The efficacy of Ginkgo special extract EGb 761 in patients with tinnitus Int J Clin Pharmacol Ther. 2002;40:188–97
42. Patterson MB, Balough BJ. Review of pharmacological therapy for tinnitus Int Tinnitus J. 2006;12:149–59
43. Swain SK, Panda S, Jena PP. Hearing loss and tinnitus among pediatric patients with COVID-19 infection: Our experience MGM J Med Sci. 2022;9:66–71
44. Liu HB, Fan JP, Lin SZ, Zhao SW, Lin Z. Botox transient treatment of tinnitus due to stapedius myoclonus: Case report Clin Neurol Neurosurg. 2011;113:57–8
45. Bennett M, Kertesz T, Yeung P. Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss and tinnitus: A systematic review of randomized controlled trials J Laryngol Otol. 2005;119:791–8
46. Sun W, Ding DL, Wang P, Sun J, Jin X, Salvi RJ. Substance P inhibits potassium and calcium currents in inner ear spiral ganglion neurons Brain Res. 2004;1012:82–92

Ginkgobiloba; lidocaine; pharmacological treatment; tinnitus

© 2022 Matrix Science Pharma | Published by Wolters Kluwer – Medknow