Artículo

Langguth, B.; Salvi, R.; Elgoyhen, A.B. "Emerging pharmacotherapy of tinnitus" (2009) Expert Opinion on Emerging Drugs. 14(4):687-702
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Abstract:

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.

Registro:

Documento: Artículo
Título:Emerging pharmacotherapy of tinnitus
Autor:Langguth, B.; Salvi, R.; Elgoyhen, A.B.
Filiación:University of Regensburg, Interdisciplinary Tinnitus Clinic, Department of Psychiatry and Psychotherapy, Universitaetsstraße 84, 93053 Regensburg, Germany
University at Buffalo, Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, Buffalo, 14214 NY, United States
Departamento de Farmacologa, Universidad de Buenos Aires, Instituto de Investigaciones en Ingeniera Gentica y Biologa Molecular (INGEBI), Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:Anticonvulsants; Antidepressants; Anxiolytics; Auditory system; GABA; Glutamate; Hearing; Inner ear; NMDA; Pain; Phantom perception; acamprosate; acetylsalicylic acid; amitriptyline; anticonvulsive agent; antidepressant agent; benzodiazepine derivative; betahistine; carbamazepine; caroverine; cinnarizine; clonazepam; dihydroergocristine; dihydroergocryptine; dopamine receptor blocking agent; dopamine receptor stimulating agent; flunarizine; Ginkgo biloba extract; lidocaine; melatonin; neramexane; nicergoline; nimodipine; pentoxifylline; piracetam; piribedil; placebo; prednisolone; sulpiride; tocainide; unindexed drug; alcoholism; anxiety; auditory stimulation; clinical feature; clinical trial; cognitive therapy; depression; drug blood level; drug mechanism; drug research; heart arrhythmia; human; insomnia; low drug dose; nonhuman; off label drug use; quality of life; review; subarachnoid hemorrhage; tinnitus; Antineoplastic Combined Chemotherapy Protocols; Anxiety; Body Mass Index; Cognition Disorders; Cognitive Therapy; Depression; Depressive Disorder; Health Status; Humans; Irritable Mood; Lung Neoplasms; Quality of Life; Questionnaires; Randomized Controlled Trials as Topic; Receptors, Cannabinoid; Risk Factors; Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic; Time Factors; Tinnitus; United States; United States Food and Drug Administration
Año:2009
Volumen:14
Número:4
Página de inicio:687
Página de fin:702
DOI: http://dx.doi.org/10.1517/14728210903206975
Título revista:Expert Opinion on Emerging Drugs
Título revista abreviado:Expert Opin. Emerg. Drugs
ISSN:14728214
CODEN:EOEDA
CAS:acamprosate, 77337-73-6; acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; amitriptyline, 50-48-6, 549-18-8; betahistine, 5579-84-0, 5638-76-6; carbamazepine, 298-46-4, 8047-84-5; caroverine, 23465-76-1, 55750-05-5; cinnarizine, 298-57-7; clonazepam, 1622-61-3; dihydroergocristine, 17479-19-5; dihydroergocryptine, 14271-05-7, 25447-66-9; flunarizine, 30484-77-6, 52468-60-7; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; melatonin, 73-31-4; neramexane, 209185-99-9, 219810-59-0, 457068-92-7; nicergoline, 27848-84-6; nimodipine, 66085-59-4; pentoxifylline, 6493-05-6; piracetam, 7491-74-9; piribedil, 3605-01-4; prednisolone, 50-24-8; sulpiride, 15676-16-1; tocainide, 41708-72-9; Receptors, Cannabinoid
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14728214_v14_n4_p687_Langguth

Referencias:

  • Henry, J.A., Dennis, K.C., Schechter, M.A., General review of tinnitus: Prevalence, mechanisms, effects, and management (2005) J Speech Lang Hear Res, 48 (5), pp. 1204-1235
  • Axelsson, A., Ringdahl, A., Tinnitus-a study of its prevalence and characteristics (1989) Br J Audiol, 23 (1), pp. 53-62
  • Hoffman, H.J., Reed, G.W., Epidemiology of Tinnitus (2004) Tinnitus: Theory and Management, pp. 16-41. , Snow JB, editor, London: BC Decker
  • Vio, M.M., Holme, R.H., Hearing loss and tinnitus: 250 million people and a US$10 billion potential market (2005) Drug Discov Today, 10 (19), pp. 1263-1265
  • Norena, A., Micheyl, C., Chery-Croze, S., Collet, L., Psychoacoustic characterization of the tinnitus spectrum: Implications for the underlying mechanisms of tinnitus (2002) Audiol Neurootol, 7 (6), pp. 358-369
  • Roberts, L.E., Moffat, G., Bosnyak, D.J., Residual inhibition functions in relation to tinnitus spectra and auditory threshold shift (2006) Acta Otolaryngol Suppl, 556, pp. 27-33
  • Konig, O., Schaette, R., Kempter, R., Gross, M., Course of hearing loss and occurrence of tinnitus (2006) Hear Res, 221 (1-2), pp. 59-64
  • House, J.W., Brackmann, D.E., Tinnitus: Surgical treatment (1981) Ciba Found Symp, 85, pp. 204-216
  • Heller, M.F., Bergman, M., Tinnitus aurium in normally hearing persons (1953) Ann Otol Rhinol Laryngol, 62 (1), pp. 73-83
  • Del Bo, L., Forti, S., Ambrosetti, U., Tinnitus aurium in persons with normal hearing: 55 years later (2008) Otolaryngol Head Neck Surg, 139 (3), pp. 391-394
  • Langguth, B., Goodey, R., Azevedo, A., Consensus for tinnitus patient assessment and treatment outcome measurement: Tinnitus Research Initiative meeting Regensburg July, 2006 (2007) Prog Brain Res, 166, pp. 525-536
  • Henry, J.A., Meikle, M.B., Psychoacoustic measures of tinnitus (2000) J Am Acad Audiol, 11, pp. 138-155
  • Vernon, J.A., Meikle, M.B., Tinnitus: Clinical measurement (2003) Otolaryngol Clin North Am, 36 (2), pp. 293-305. , vi
  • Tyler, R.S., Oleson, J., Noble, W., Clinical trials for tinnitus: Study populations, designs, measurement variables, and data analysis (2007) Prog Brain Res, 166, pp. 499-509
  • Hiller, W., Goebel, G., Factors influencing tinnitus loudness and annoyance (2006) Arch Otolaryngol Head Neck Surg, 132 (12), pp. 1323-1330
  • Jastreboff, P.J., Phantom auditory perception (tinnitus): Mechanisms of generation and perception (1990) Neurosci Res, 8, pp. 221-254
  • Moller, A.R., Pathophysiology of tinnitus (2003) Otolaryngol Clin North Am, 36, pp. 249-266
  • Bauer, C.A., Turner, J.G., Caspary, D.M., Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlear trauma (2008) J Neurosci Res, 86 (11), pp. 2564-2578
  • Eggermont, J.J., Pathophysiology of tinnitus (2007) Prog Brain Res, 166, pp. 19-35
  • Kaltenbach, J.A., The dorsal cochlear nucleus as a contributor to tinnitus: Mechanisms underlying the induction of hyperactivity (2007) Prog Brain Res, 166, pp. 89-106
  • Melcher, J.R., Sigalovsky, I.S., Guinan Jr., J.J., Levine, R.A., Lateralized tinnitus studied with functional magnetic resonance imaging: Abnormal inferior colliculus activation (2000) J Neurophysiol, 83, pp. 1058-1072
  • Reyes, S.A., Salvi, R.J., Burkard, R.F., Brain imaging of the effects of lidocaine on tinnitus (2002) Hear Res, 171, pp. 43-50
  • Langguth, B., Eichhammer, P., Kreutzer, A., The impact of auditory cortex activity on characterizing and treating patients with chronic tinnitus-first results from a PET study (2006) Acta Otolaryngol Suppl, (556), pp. 84-88
  • Smits, M., De Rd, K.S., Lateralization of functional magnetic resonance imaging (fMRI) activation in the auditory pathway of patients with lateralized tinnitus (2007) Neuroradiology, 49 (8), pp. 669-679
  • Schlee, W., Hartmann, T., Langguth, B., Weisz, N., Abnormal resting-state cortical coupling in chronic tinnitus (2009) BMC Neurosci, 10 (11)
  • Muroi, Y., Chanda, B., Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel (2009) J Gen Physiol, 133 (1), pp. 1-15
  • Trellakis, S., Lautermann, J., Lehnerdt, G., Lidocaine: Neurobiological targets and effects on the auditory system (2007) Prog Brain Res, 166, pp. 303-322
  • Cronlein, T., Langguth, B., Geisler, P., Hajak, G., Tinnitus and insomnia (2007) Prog Brain Res, 166, pp. 227-233
  • Langguth, B., Kleinjung, T., Fischer, B., Tinnitus severity, depression, and the big five personality traits (2007) Prog Brain Res, 166, pp. 221-225
  • Biassoni, E.C., Serra, M.R., Richtert, U., Recreational noise exposure and its effects on the hearing of adolescents (2005) Int J Audiol, 44 (2), pp. 74-85. , Part II: Development of hearing disorders
  • Serra, M.R., Biassoni, E.C., Richter, U., Recreational noise exposure and its effects on the hearing of adolescents (2005) Int J Audiol, 44 (2), pp. 65-73. , Part I: An interdisciplinary long-term study
  • http://www.vba.va.gov/bln/21/, Available from:; Dobie, R.A., A review of randomized clinical trials in tinnitus (1999) Laryngoscope, 109, pp. 1202-1211
  • Dobie, R., Clinical trials and drug therapy for tinnitus (2004) Tinnitus: Theory and Management, pp. 266-277. , Snow JB, editor. Hamilton: BC Decker
  • Vio, M., (2003) Tinnitus Market Situation Analysis, , London: RNID
  • Eggermont, J.J., Tinnitus: Neurobiological substrates (2005) Drug Discov Today, 10 (19), pp. 1283-1290
  • Moller, A.R., Tinnitus and pain (2007) Prog Brain Res, 166, pp. 47-53
  • Moller, A.R., A double-blind placebo-controlled trial of baclofen in the treatment of tinnitus (1997) Am J Otol, 18 (2), pp. 268-269
  • Barany, R., Die beeinflussung des ohrensausens durch intravenös injizierte lokalanästhetica (1935) Acta Otolarngologica, 23, pp. 201-203
  • Melding, P.S., Goodey, R.J., Thorne, P.R., The use of intravenous lignocaine in the diagnosis and treatment of tinnitus (1978) J Laryngol Otol, 92 (2), pp. 115-121
  • Martin, F.W., Colman, B.H., Tinnitus: A double-blind crossover controlled trial to evaluate the use of lignocaine (1980) Clin Otolaryngol, 5, pp. 3-11
  • Sanchez, T.G., Balbani, A.P., Bittar, R.S., Lidocaine test in patients with tinnitus: Rationale of accomplishment and relation to the treatment with carbamazepine (1999) Auris Nasus Larynx, 26 (4), pp. 411-417
  • Trellakis, S., Benzenberg, D., Urban, B.W., Friederich, P., Differential lidocaine sensitivity of human voltage-gated potassium channels relevant to the auditory system (2006) Otol Neurotol, 27 (1), pp. 117-123
  • Haginomori, S., Makimoto, K., Araki, M., Effect of lidocaine injection of EOAE in patients with tinnitus (1995) Acta Otolaryngol, 115 (4), pp. 488-492
  • Baguley, D.M., Jones, S., Wilkins, I., The inhibitory effect of intravenous lidocaine infusion on tinnitus after translabyrinthine removal of vestibular schwannoma: A double-blind, placebo-controlled, crossover study (2005) Otol Neurotol, 26 (2), pp. 169-176
  • Schwartz, M.L., Meyer, M.B., Covino, B.G., Antiarrhythmic effectiveness of intramuscular lidocaine: Influence of different injection sites (1974) J Clin Pharmacol, 14 (2), pp. 77-83
  • Clarkson, C.W., Follmer, C.H., Eick, T., Evidence for two components of sodium channel block by lidocaine in isolated cardiac myocytes (1988) Circ Res, 63 (5), pp. 869-878
  • Courtney, K.R., Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA (1975) J Pharmacol Exp Ther, 195 (2), pp. 225-236
  • Lenkowski, P.W., Shah, B.S., Dinn, A.E., Lidocaine block of neonatal Nav1.3 is differentially modulated by co-expression of beta1 and beta3 subunits (2003) Eur J Pharmacol, 467 (1-3), pp. 23-30
  • Josephson, I.R., Lidocaine blocks Na, Ca and K currents of chick ventricular myocytes (1988) J Mol Cell Cardiol, 20 (7), pp. 593-604
  • Plewnia, C., Reimold, M., Najib, A., Dose-dependent attenuation of auditory phantom perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation (2007) Hum Brain Mapp, 28 (3), pp. 238-246
  • Hulshof, J.H., Vermeij, P., The value of tocainide in the treatment of tinnitus (1985) Arch Otorhinolaryngol, 241, pp. 279-283. , A double-blind controlled study
  • Blayney, A.W., Phillips, M.S., Guy, A.M., Colman, B.H., A sequential double blind cross-over trial of tocainide hydrochloride in tinnitus (1985) Clin Otolaryngol, 10, pp. 97-101
  • Lenarz, Th., Treatment of tinnitus with lidocaine and tocainide (1987) Scandinavian Audiology, SUPPL. 26, pp. 49-51
  • Sieghart, W., Pharmacology of benzodiazepine receptors: An update (1994) J Psychiatry Neurosci, 19 (1), pp. 24-29
  • Johnson, R.M., Brummett, R., Schleuning, A., (1993) Use of alprazolam for relief of tinnitus, 119 (8), pp. 842-845. , A double-blind study Arch Otolaryngol Head Neck Surg
  • Kay, N.J., Oral chemotherapy in tinnitus (1981) Br J Audiol, 15 (2), pp. 123-124
  • Gananca, M.M., Caovilla, H.H., Gananca, F.F., Clonazepam in the pharmacological treatment of vertigo and tinnitus (2002) Int Tinnitus J, 8 (1), pp. 50-53
  • Bahmad Jr., F.M., Venosa, A.R., Oliveira, C.A., Benzodiazepines and GABAergics in treating severe disabling tinnitus of predominantly cochlear origin (2006) Int Tinnitus J, 12 (2), pp. 140-144
  • Busto, U., Fornazzari, L., Naranjo, C.A., Protracted tinnitus after discontinuation of long-term therapeutic use of benzodiazepines (1988) J Clin Psychopharmacol, 8 (5), pp. 359-362
  • Busto, U., Sellers, E.M., Naranjo, C.A., Withdrawal reaction after long-term therapeutic use of benzodiazepines (1986) N Engl J Med, 315 (14), pp. 854-859
  • Moller, A.R., Similarities between severe tinnitus and chronic pain (2000) J Am Acad Audiol, 11, pp. 115-124
  • Gross, G., Xin, X., Gastpar, M., Trimipramine: Pharmacological reevaluation and comparison with clozapine (1991) Neuropharmacology, 30 (11), pp. 1159-1166
  • Bayar, N., Boke, B., Turan, E., Belgin, E., Efficacy of amitriptyline in the treatment of subjective tinnitus (2001) J Otolaryngol, 30 (5), pp. 300-303
  • Podoshin, L., Ben-David, Y., Fradis, M., Idiopathic subjective tinnitus treated by amitriptyline hydrochloride/biofeedback (1995) Int Tinnitus J, 1 (1), pp. 54-60
  • Sullivan, M.D., Dobie, R.A., Sakai, C.S., Katon, W.J., Treatment of depressed tinnitus patients with nortriptyline (1989) Ann Otol Rhinol Laryngol, 98 (11), pp. 867-872
  • Sullivan, M., Katon, W., Russo, J., A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms (1993) Arch Intern Med, 153 (19), pp. 2251-2259
  • Katon, W., Sullivan, M., Russo, J., Depressive symptoms and measures of disability: A prospective study (1993) J Affect Disord, 27 (4), pp. 245-254
  • Mihail, R.C., Crowley, J.M., Walden, B.E., The tricyclic trimipramine in the treatment of subjective tinnitus (1988) Ann Otol Rhinol Laryngol, 97 (2 PART 1), pp. 120-123
  • Mendis, D., Johnston, M., An unusual case of prolonged tinnitus following low-dose amitriptyline (2008) J Psychopharmacol, 22 (5), pp. 574-575
  • Feder, R., Tinnitus associated with amitriptyline (1990) J Clin Psychiatry, 51 (2), pp. 85-86
  • Tandon, R., Grunhaus, L., Greden, J.F., Imipramine and tinnitus (1987) J Clin Psychiatry, 48 (3), pp. 109-111
  • Robinson, S.K., Viirre, E.S., Bailey, K.A., Randomized placebo-controlled trial of a selective serotonin reuptake inhibitor in the treatment of nondepressed tinnitus subjects (2005) Psychosom Med, 67 (6), pp. 981-988
  • Zoger, S., Svedlund, J., Holgers, K.M., The effects of sertraline on severe tinnitus suffering-a randomized, double-blind, placebo-controlled study (2006) J Clin Psychopharmacol, 26 (1), pp. 32-39
  • Robinson, S., Antidepressants for treatment of tinnitus (2007) Prog Brain Res, 166, pp. 263-271
  • Willow, M., Gonoi, T., Catterall, W.A., Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells (1985) Mol Pharmacol, 27 (5), pp. 549-558
  • Cardenas, C.A., Cardenas, C.G., De Armendi, A.J., Scroggs, R.S., Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels (2006) Neurosci Lett, 408 (2), pp. 129-134
  • Shea, J.J., Harell, M., Management of tinnitus aurium with lidocaine and carbamazepine (1978) Laryngoscope, 88 (9 PART 1), pp. 1477-1484
  • Melding, P.S., Goodey, R.J., The treatment of tinnitus with oral anticonvulsants (1979) J Laryngol Otol, 93 (2), pp. 111-122
  • Donaldson, I., Tegretol: A double blind trial in tinnitus (1981) J Laryngol Otol, 95 (9), pp. 947-951
  • Hulshof, J.H., Vermeij, P., The value of carbamazepine in the treatment of tinnitus (1985) ORL J Otorhinolaryngol Relat Spec, 47, pp. 262-266
  • Marks, N.J., Onisiphorou, C., Trounce, J.R., The effect of single doses of amylobarbitone sodium and carbamazepine in tinnitus (1981) J Laryngol Otol, 95 (9), pp. 941-945
  • Levine, R.A., Typewriter tinnitus: A carbamazepine-responsive syndrome related to auditory nerve vascular compression (2006) ORL J Otorhinolaryngol Relat Spec, 68 (1), pp. 43-46
  • Mardini, M.K., Ear-clicking "tinnitus" responding to carbamazepine (1987) N Engl J Med, 317 (24), p. 1542
  • Zheng, Y., Hooton, K., Smith, P.F., Darlington, C.L., Carbamazepine reduces the behavioural manifestations of tinnitus following salicylate treatment in rats (2008) Acta Otolaryngol, 128 (1), pp. 48-52
  • Zapp, J.J., Gabapentin for the treatment of tinnitus: A case report (2001) Ear Nose Throat J, 80 (2), pp. 114-116
  • Shulman, A., Gabapentin and tinnitus relief (2008) Int Tinnitus J, 14 (1), pp. 1-5
  • Bauer, C.A., Brozoski, T.J., Assessing tinnitus and prospective tinnitus therapeutics using a psychophysical animal model (2001) J Assoc Res Otolaryngol, 2 (1), pp. 54-64
  • Witsell, D.L., Hannley, M.T., Stinnet, S., Tucci, D.L., Treatment of tinnitus with gabapentin: A pilot study (2007) Otol Neurotol, 28 (1), pp. 11-15
  • Bakhshaee, M., Ghasemi, M., Azarpazhooh, M., Gabapentin effectiveness on the sensation of subjective idiopathic tinnitus: A pilot study (2008) Eur Arch Otorhinolaryngol, 265 (5), pp. 525-530
  • Piccirillo, J.F., Finnell, J., Vlahiotis, A., Relief of idiopathic subjective tinnitus: Is gabapentin effective? (2007) Arch Otolaryngol Head Neck Surg, 133 (4), pp. 390-397
  • Bauer, C.A., Brozoski, T.J., Effect of gabapentin on the sensation and impact of tinnitus (2006) Laryngoscope, 116 (5), pp. 675-681
  • Brozoski, T.J., Spires, T.J., Bauer, C.A., Vigabatrin, a GABA transaminase inhibitor, reversibly eliminates tinnitus in an animal model (2007) J Assoc Res Otolaryngol, 8 (1), pp. 105-118
  • Willmore, L.J., Abelson, M.B., Ben-Menachem, E., Vigabatrin: 2008 update (2009) Epilepsia, 50 (2), pp. 163-173
  • Oestreicher, E., Arnold, W., Ehrenberger, K., Felix, D., Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair cells (1998) ORL J Otorhinolaryngol Relat Spec, 60 (1), pp. 18-21
  • Guitton, M.J., Caston, J., Ruel, J., Salicylate induces tinnitus through activation of cochlear NMDA receptors (2003) J Neurosci, 23 (9), pp. 3944-3952
  • Guitton, M.J., Dudai, Y., Blockade of cochlear NMDA receptors prevents long-term tinnitus during a brief consolidation window after acoustic trauma (2007) Neural Plast, 2007, p. 80904
  • Jastreboff, P.J., Brennan, J.F., Coleman, J.K., Sasaki, C.T., Phantom auditory sensation in rats: An animal model for tinnitus (1988) Behav Neurosci, 102 (6), pp. 811-822
  • Peng, B.G., Chen, S., Lin, X., Aspirin selectively augmented N-methyl-D-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice (2003) Neurosci Lett, 343 (1), pp. 21-24
  • Ehrenberger, K., Felix, D., Receptor pharmacological models for inner ear therapies with emphasis on glutamate receptors: A survey (1995) Acta Otolaryngol, 115, pp. 236-240
  • Denk, D.M., Heinzl, H., Franz, P., Ehrenberger, K., Caroverine in tinnitus treatment (1997) Acta Otolaryngol, 117 (6), pp. 825-830. , A placebo-controlled blind study
  • Domeisen, H., Hotz, M.A., Hausler, R., Caroverine in tinnitus treatment (1998) Acta Otolaryngol, 118 (4), pp. 606-608
  • Rogawski, M.A., Wenk, G.L., The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease (2003) CNS Drug Rev, 9 (3), pp. 275-308
  • Rammes, G., Rupprecht, R., Ferrari, U., The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner (2001) Neurosci Lett, 306 (1-2), pp. 81-84
  • Oliver, D., Ludwig, J., Reisinger, E., Memantine inhibits efferent cholinergic transmission in the cochlea by blocking nicotinic acetylcholine receptors of outer hair cells (2001) Mol Pharmacol, 60 (1), pp. 183-189
  • Lobarinas, E., Yang, G., Sun, W., Salicylate- and quinine-induced tinnitus and effects of memantine (2006) Acta Otolaryngol Suppl, (556), pp. 13-19
  • Figueiredo, R.R., Langguth, B., De Oliveira, P.M., De Azevedo, A.A., Tinnitus treatment with memantine (2008) Otolaryngol Head Neck Surg, 138 (4), pp. 492-496
  • Salembier, L., De Ridder, D., Van De Heyning, P.H., The use of flupirtine in treatment of tinnitus (2006) Acta Otolaryngol Suppl, 556, pp. 93-95
  • Williams, S.H., Medications for treating alcohol dependence (2005) Am Fam Physician, 72 (9), pp. 1775-1780
  • Azevedo, A.A., Figueiredo, R.R., Treatment of tinnitus with acamprosate (2007) Prog Brain Res, 166, pp. 273-277
  • http://clinicaltrials.gov/ct2/show/NCT00596531, Available from:; Jastreboff, P.J., Hazell, J.W., A neurophysiological approach to tinnitus: Clinical implications (1993) Br J Audiol, 27 (1), pp. 7-17
  • Lockwood, A.H., Salvi, R.J., Coad, M.L., The functional neuroanatomy of tinnitus: Evidence for limbic system links and neural plasticity (1998) Neurology, 50 (1), pp. 114-120
  • Larson, E.R., Ariano, M.A., D3 and D2 dopamine receptors: Visualization of cellular expression patterns in motor and limbic structures (1995) Synapse, 20 (4), pp. 325-337
  • Memo, M., Battaini, F., Spano, P.F., Trabucchi, M., Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics (1981) Acta Psychiatr Scand, 63 (4), pp. 314-324
  • Lopez-Gonzalez, M.A., Santiago, A.M., Esteban-Ortega, F., Sulpiride and melatonin decrease tinnitus perception modulating the auditolimbic dopaminergic pathway (2007) J Otolaryngol, 36 (4), pp. 213-219
  • Lopez-Gonzalez, M.A., Moliner-Peiro, F., Faro-Garcia, J., Esteban-Ortega, F., Sulpiride plus hydroxyzine decrease tinnitus perception (2007) Auris Nasus Larynx, 34 (1), pp. 23-27
  • Hastak, S.M., Treatment of memory impairment, vertigo and tinnitus in the elderly with piribedil in an Indian general practice setting (2003) J Indian Med Assoc, 101 (8), pp. 500-501
  • Slattery, W.H., Fisher, L.M., Iqbal, Z., Friedman, R.A., Liu, N., Intratympanic steroid injection for treatment of idiopathic sudden hearing loss (2005) Otolaryngology - Head and Neck Surgery, 133 (2), pp. 251-259. , DOI 10.1016/j.otohns.2005.05.015, PII S0194599805005802
  • Azevedo, A.A., Langguth, B., De Oliveira, P.M., Figueiredo, R.R., Tinnitus treatment with piribedil guided by electrocochleography and acoustic otoemisions (2009) Otol Neurotol in Press
  • Slattery, W.H., Fisher, L.M., Iqbal, Z., Liu, N., Oral steroid regimens for idiopathic sudden sensorineural hearing loss (2005) Otolaryngology - Head and Neck Surgery, 132 (1), pp. 5-10. , DOI 10.1016/j.otohns.2004.09.072, PII S0194599804018558
  • Haynes, D.S., O'Malley, M., Cohen, S., Intratympanic dexamethasone for sudden sensorineural hearing loss after failure of systemic therapy (2007) Laryngoscope, 117 (1), pp. 3-15
  • Wei, B.P.C., Mubiru, S., O'Leary, S., Steroids for idiopathic sudden sensorineural hearing loss (2006) Cochrane Database Syst Rev, (1)
  • Mahadevan, S., Park, Y., Multifaceted therapeutic benefits of Ginkgo biloba L: Chemistry, efficacy, safety, and uses (2008) J Food Sci, 73 (1), pp. R14-R19
  • Morgenstern, C., Biermann, E., The efficacy of Ginkgo special extract EGb 761 in patients with tinnitus (2002) Int J Clin Pharmacol Ther, 40 (5), pp. 188-197
  • Holstein, N., Ginkgo special extract EGb 761 in tinnitus therapy. An overview of results of completed clinical trials (2001) Fortschr Med Orig, 118, pp. 157-164
  • Drew, S., Davies, E., Effectiveness of Ginkgo biloba in treating tinnitus: Double blind, placebo controlled trial (2001) BMJ, 322 (7278), p. 73
  • Rejali, D., Sivakumar, A., Balaji, N., Ginkgo biloba does not benefit patients with tinnitus: A randomized placebo-controlled double-blind trial and meta-analysis of randomized trials (2004) Clin Otolaryngol Allied Sci, 29 (3), pp. 226-231
  • Hilton, M., Stuart, E., Ginkgo biloba for tinnitus (2004) Cochrane Database Syst Rev, 2, pp. CD003852
  • Jan, J.E., Reiter, R.J., Wasdell, M.B., Bax, M., The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders (2009) J Pineal Res, 46 (1), pp. 1-7
  • Seggie, J., Werstiuk, E.S., Grota, L., Lithium and circadian patterns of melatonin in the retina, hypothalamus, pineal and serum (1987) Prog Neuropsychopharmacol Biol Psychiatry, 11 (2-3), pp. 325-334
  • Berra, B., Rizzo, A.M., Melatonin: Circadian rhythm regulator, chronobiotic, antioxidant and beyond (2009) Clin Dermatol, 27 (2), pp. 202-209
  • Lopez-Gonzalez, M.A., Guerrero, J.M., Rojas, F., Delgado, F., Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants (2000) J Pineal Res, 28 (2), pp. 73-80
  • Bas, E., Martinez-Soriano, F., Lainez, J.M., Marco, J., An experimental comparative study of dexamethasone, melatonin and tacrolimus in noise-induced hearing loss (2009) Acta Otolaryngol, 129 (4), pp. 385-389
  • Megwalu, U.C., Finnell, J.E., Piccirillo, J.F., The effects of melatonin on tinnitus and sleep (2006) Otolaryngol Head Neck Surg, 134 (2), pp. 210-213
  • Rosenberg, S.I., Silverstein, H., Rowan, P.T., Olds, M.J., Effect of melatonin on tinnitus (1998) Laryngoscope, 108 (3), pp. 305-310
  • McFadden, S.L., Ding, D., Burkard, R.F., Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice (1999) J Comp Neurol, 413 (1), pp. 101-112
  • Zirpel, L., Parks, T.N., Zinc inhibition of group i mGluR-mediated calcium homeostasis in auditory neurons (2001) J Assoc Res Otolaryngol, 2 (2), pp. 180-187
  • Shambaugh, G.E., Zinc for tinnitus, imbalance, and hearing loss in the elderly (1986) Am J Otol, 7 (6), pp. 476-477
  • Coelho, C.B., Tyler, R., Hansen, M., Zinc as a possible treatment for tinnitus (2007) Prog Brain Res, 166, pp. 279-285
  • Paaske, P.B., Pedersen, C.B., Kjems, G., Sam, I.L., Zinc in the management of tinnitus. Placebo-controlled trial (1991) Ann Otol Rhinol Laryngol, 100 (8), pp. 647-649
  • Yetiser, S., Tosun, F., Satar, B., The role of zinc in management of tinnitus (2002) Auris Nasus Larynx, 29 (4), pp. 329-333
  • Roth, S.H., Misoprostol in the prevention of NSAID-induced gastric ulcer: A multicenter, double-blind, placebo-controlled trial (1990) J Rheumatol Suppl, 20, pp. 20-24
  • Briner, W., House, J., O'Leary, M., Synthetic prostaglandin E1 misoprostol as a treatment for tinnitus (1993) Arch Otolaryngol Head Neck Surg, 119 (6), pp. 652-654
  • Yilmaz, I., Akkuzu, B., Cakmak, O., Ozluoglu, L.N., Misoprostol in the treatment of tinnitus: A double-blind study (2004) Otolaryngol Head Neck Surg, 130 (5), pp. 604-610
  • Gresser, U., Gathof, B.S., Atorvastatin: Gold standard for prophylaxis of myocardial ischemia and stroke - Comparison of the clinical benefit of statins on the basis of randomized controlled endpoint studies (2004) Eur J Med Res, 9 (1), pp. 1-17
  • Olzowy, B., Canis, M., Hempel, J.M., Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus in the elderly: Results of a prospective, randomized, double-blind clinical trial (2007) Otol Neurotol, 28 (4), pp. 455-458
  • Scriabine, A., Van Den, K.W., Pharmacology of nimodipine. A review (1988) Ann NY Acad Sci, 522, pp. 698-706
  • Keyrouz, S.G., Diringer, M.N., Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage (2007) Crit Care, 11 (4), p. 220
  • Goodnick, P.J., Nimodipine treatment of rapid cycling bipolar disorder (1995) J Clin Psychiatry, 56 (7), p. 330
  • Jastreboff, P.J., Brennan, J.F., Sasaki, C.T., Quinine-induced tinnitus in rats (1991) Arch Otolaryngol Head Neck Surg, 117 (10), pp. 1162-1166
  • Theopold, H.M., Nimodipine (Bay e 9736) a new therapy concept in diseases of the inner ear? (1985) Laryngol Rhinol Otol (Stuttg), 64 (12), pp. 609-613
  • Davies, E., Knox, E., Donaldson, I., The usefulness of nimodipine, an L-calcium channel antagonist, in the treatment of tinnitus (1994) Br J Audiol, 28 (3), pp. 125-129
  • Hutcheon, D.E., Leonard, G., Diuretic and antihypertensive actions of furosemide (1967) J Clin Pharmacol J New Drugs, 7 (1), pp. 26-33
  • Shiozaki, A., Miyazaki, H., Niisato, N., Furosemide, a blocker of Na+/K+/2Cl-cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state (2006) J Physiol Sci, 56 (6), pp. 401-406
  • Sakaguchi, N., Crouch, J.J., Lytle, C., Schulte, B.A., Na-K-Cl cotransporter expression in the developing and senescent gerbil cochlea (1998) Hear Res, 118 (1-2), pp. 114-122
  • Chen, H., Sun, D., The role of Na-K-Cl co-transporter in cerebral ischemia (2005) Neurol Res, 27 (3), pp. 280-286
  • Rybak, L.P., Morizono, T., Effect of furosemide upon endolymph potassium concentration (1982) Hear Res, 7 (2), pp. 223-231
  • Futaki, T., Kitahara, M., Morimoto, M., A comparison of the furosemide and glycerol tests for Meniere's disease. With special reference to the bilateral lesion (1977) Acta Otolaryngol, 83 (3-4), pp. 272-278
  • Kuchar, D.L., O'Rourke, M.F., High dose furosemide in refractory cardiac failure (1985) Eur Heart J, 6 (11), pp. 954-958
  • Ho, K.M., Sheridan, D.J., Meta-analysis of frusemide to prevent or treat acute renal failure (2006) BMJ, 333 (7565), p. 420
  • Filipo, R., Barbara, M., Cordier, A., Osmotic drugs in the treatment of cochlear disorders: A clinical and experimental study (1997) Acta Otolaryngol, 117 (2), pp. 229-231
  • McCabe, B.F., Central aspects of drugs for motion sickness and vertigo (1973) Adv Otorhinolaryngol, 20, pp. 458-469
  • Kranke, P., Morin, A.M., Roewer, N., Wulf, H., Eberhart, L.H., The efficacy and safety of transdermal scopolamine for the prevention of postoperative nausea and vomiting: A quantitative systematic review (2002) Anesthesia and Analgesia, 95 (1), pp. 133-143
  • Wallhausser-Franke, E., Cuautle-Heck, B., Scopolamine attenuates tinnitus-related plasticity in the auditory cortex (2006) Neuroreport, 17 (14), pp. 1487-1491
  • Lobarinas, E., Sun, W., Stolzberg, D., Human brain imaging of tinnitus and animal models (2008) Semin Hear, 29 (4), pp. 333-349
  • Timmerman, H., Calcium modulation and clinical effect. Profile of cyclandelate (1987) Drugs, 33 (SUPPL. 2), pp. 1-4
  • Memin, Y., Perceived efficacy of cyclandelate in the treatment of cochleovestibular and retinal disturbances related to cerebrovascular insufficiency (1987) Drugs, 33 (SUPPL.), pp. 120-124. , A study in general practice comprising 2772 patients
  • Hester, T.O., Theilman, G., Green, W., Jones, R.O., Cyclandelate in the management of tinnitus: A randomized, placebo-controlled study (1998) Otolaryngol Head Neck Surg, 118 (3 PART 1), pp. 329-332
  • Stidham, K.R., Solomon, P.H., Roberson, J.B., Evaluation of botulinum toxin A in treatment of tinnitus (2005) Otolaryngol Head Neck Surg, 132 (6), pp. 883-889
  • Penney, S.E., Bruce, I.A., Saeed, S.R., Botulinum toxin is effective and safe for palatal tremor: A report of five cases and a review of the literature (2006) J Neurol, 253 (7), pp. 857-860
  • Adjamian, P., Sereda, M., Hall, D.A., The mechanisms of tinnitus: Perspectives from human functional neuroimaging (2009) Hear Res, 253, pp. 15-31
  • Turner, J.G., Behavioral measures of tinnitus in laboratory animals (2007) Prog Brain Res, 166, pp. 147-156
  • Arnold, W., Bartenstein, P., Oestreicher, E., Focal metabolic activation in the predominant left auditory cortex in patients suffering from tinnitus: A PET study with [18F]deoxyglucose (1996) ORL J Otorhinolaryngol Relat Spec, 58, pp. 195-199
  • Muhlnickel, W., Elbert, T., Taub, E., Flor, H., Reorganization of auditory cortex in tinnitus (1998) Proc Natl Acad Sci USA, 95, pp. 10340-10343
  • Sun, W., Lu, J., Stolzberg, D., Salicylate increases the gain of the central auditory system (2009) Neuroscience, 159 (1), pp. 325-334
  • Moller, A.R., The role of neural plasticity in tinnitus (2007) Prog Brain Res, 166, pp. 37-45
  • De Ridder, D., Verstraeten, E., Van Der, K.K., Transcranial magnetic stimulation for tinnitus: Influence of tinnitus duration on stimulation parameter choice and maximal tinnitus suppression (2005) Otol Neurotol, 26 (4), pp. 616-619
  • De Ridder, D., Van Der Loo, E., Van Der Kelen, K., Do tonic and burst TMS modulate the lemniscal and extralemniscal system differentially? (2007) Int J Med Sci, 4 (5), pp. 242-246
  • Tyler, R., Coelho, C., Tao, P., Identifying tinnitus subgroups with cluster analysis (2008) Am J Audiol, 17 (2), pp. S176-S184
  • Tyler, R.S., Oleson, J., Noble, W., Clinical trials for tinnitus: Study populations, designs, measurement variables, and data analysis (2007) Prog Brain Res, 166, pp. 499-509
  • Elgoyhen, A.B., Vetter, D.E., Katz, E., Alpha10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells (2001) Proc Natl Acad Sci USA, 98 (6), pp. 3501-3506
  • Elgoyhen, A.B., Johnson, D.S., Boulter, J., Alpha 9: An acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells (1994) Cell, 79 (4), pp. 705-715
  • Plazas, P.V., Savino, J., Kracun, S., Inhibition of the alpha9alpha10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-D-aspartate receptors (2007) Eur J Pharmacol, 566 (1-3), pp. 11-19
  • http://clinicaltrials.gov/ct2/show/NCT00405886, Available from:; http://clinicaltrials.gov/ct2/show/NCT00739635, Available from: http://clinicaltrials.gov/ct2/show/NCT00772980, http://clinicaltrials.gov/ct2/show/NCT00827008; http://clinicaltrials.gov/ct2/show/NCT00860808, Available from:; Sun, W., Ding, D.L., Wang, P., Substance P inhibits potassium and calcium currents in inner ear spiral ganglion neurons (2004) Brain Res, 1012 (1-2), pp. 82-92
  • http://clinicaltrials.gov/ct2/show/NCT00394056, Available from:; Carpenter, W.T., Koenig, J.I., The evolution of drug development in schizophrenia: Past issues and future opportunities (2008) Neuropsychopharmacology, 33 (9), pp. 2061-2079
  • De Ridder, D., Fransen, H., Francois, O., Amygdalohippocampal involvement in tinnitus and auditory memory (2006) Acta Otolaryngol Suppl, 556, pp. 50-53
  • Yang, G., Lobarinas, E., Zhang, L., Salicylate induced tinnitus: Behavioral measures and neural activity in auditory cortex of awake rats (2007) Hear Res, 226 (1-2), pp. 244-253
  • Lobarinas, E., Sun, W., Cushing, R., Salvi, R., A novel behavioral paradigm for assessing tinnitus using schedule-induced polydipsia avoidance conditioning (SIP-AC) (2004) Hear Res, 190 (1-2), pp. 109-114
  • Hurko, O., Ryan, J.L., Translational research in central nervous system drug discovery (2005) Neuro Rx, 2 (4), pp. 671-682
  • Meikle, M.B., Vernon, J., Johnson, R.M., The perceived severity of tinnitus. Some observations concerning a large population of tinnitus clinic patients (1984) Otolaryngol Head Neck Surg, 92 (6), pp. 689-696
  • Jakes, S.C., Hallam, R.S., Chambers, C., Hinchcliffe, R., A factor analytical study of tinnitus complaint behaviour (1985) Audiology, 24 (3), pp. 195-206
  • Newman, C.W., Sandridge, S.A., Jacobson, G.P., Psychometric adequacy of the Tinnitus Handicap Inventory (THI) for evaluating treatment outcome (1998) J Am Acad Audiol, 9 (2), pp. 153-160
  • Goebel, G., Hiller, W., The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire (1994) Hno, 42, pp. 166-172
  • Kuk, F.K., Tyler, R.S., Russell, D., Jordan, H., The psychometric properties of a tinnitus handicap questionnaire (1990) Ear Hear, 11 (6), pp. 434-445

Citas:

---------- APA ----------
Langguth, B., Salvi, R. & Elgoyhen, A.B. (2009) . Emerging pharmacotherapy of tinnitus. Expert Opinion on Emerging Drugs, 14(4), 687-702.
http://dx.doi.org/10.1517/14728210903206975
---------- CHICAGO ----------
Langguth, B., Salvi, R., Elgoyhen, A.B. "Emerging pharmacotherapy of tinnitus" . Expert Opinion on Emerging Drugs 14, no. 4 (2009) : 687-702.
http://dx.doi.org/10.1517/14728210903206975
---------- MLA ----------
Langguth, B., Salvi, R., Elgoyhen, A.B. "Emerging pharmacotherapy of tinnitus" . Expert Opinion on Emerging Drugs, vol. 14, no. 4, 2009, pp. 687-702.
http://dx.doi.org/10.1517/14728210903206975
---------- VANCOUVER ----------
Langguth, B., Salvi, R., Elgoyhen, A.B. Emerging pharmacotherapy of tinnitus. Expert Opin. Emerg. Drugs. 2009;14(4):687-702.
http://dx.doi.org/10.1517/14728210903206975