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Intratympanic Dexamethasone Injections
as a Treatment for Severe, Disabling Tinnitus
Does It Work?
Mercedes F. S. Araújo, MD, MSc; Carlos A. Oliveira, MD, PhD; Fayez M. Bahmad, Jr, MD Objective: To test the effectiveness of intratympanic
Main Outcome Measure: Improvement of tinnitus
dexamethasone injections as a treatment for severe dis- measured with a visual analog scale.
Results: The 2 groups were similar in age, sex, tinnitus
Design: Randomized, prospective, single-blind study.
laterality, measurement of tinnitus intensity on the visualanalog scale, and main otologic diagnosis. We considered Setting: Academic tertiary referral hospital.
a 2-point improvement on the visual analog scale to be sig-nificant. Twenty-nine percent of the ears in the saline group Patients: Thirty-six patients with severe disabling
and 33% of the ears in the dexamethasone group showed tinnitus predominantly of cochlear origin were ran- significant improvement immediately after completion of domly assigned to receive intratympanic injections treatment. These measurements were not significantly dif- of a dexamethasone solution or isotonic sodium chlo- ferent from each other. Follow-up varied from 13 to 31 months, and the patients with improved tinnitus returnedto the initial measurements over time.
Interventions: Under topical anesthesia and after
randomization, 36 patients received 0.5-mL intratym-
Conclusions: There was no advantage in intratym-
panic injections once per week for 4 weeks of either a panic injections of dexamethasone over saline solution 4-mg/mL dexamethasone solution or saline solution.
in the treatment of severe, disabling tinnitus. Both solu- Five patients were excluded from analysis because tions produced a placebolike improvement.
they did not complete the treatment or did not returnfor follow-up.
Arch Otolaryngol Head Neck Surg. 2005;131:113-117 IN1982SAKATAETAL1TREATED tinnitus,andtheintensityofthesymp-
toms was characterized as severe and dis- tus control for at least 1 year and 2 had tinnitus control for only a few hours. Three treated 1214 patients (1466 ears) with tin- patients experienced no improvement.
nitus of presumed cochlear origin with in- tratympanic dexamethasone injections.
tients treated with intratympanic dexameth- asone injections. They used chemical tests (COM), labyrinthine syphilis, Ménière’s pine) to establish a cochlear origin for the tion, acoustic trauma, head injury, or other enced complete resolution of tinnitus, 40% otological diseases. The authors reported good overall results in 77% of the ears im- after 6 months. Ears with COM, Ménière’s tion was present in only 13.5% of the pa- disease, and labyrinthine syphilis had the tion, only 2 patients continued reporting Author Affiliations:
complete resolution of the symptoms.
Department of Otolaryngology,Brasília University Medical In 1999 Oliveira et al5 described the tin- asone injections. These patients were se- Financial Disclosure: None.
laryngology of Brasília University Medi- (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 131, FEB 2005 Downloaded From: http://archotol.jamanetwork.com/ on 07/04/2012
Medical Association. All rights reserved.
cal School. They administered a questionnaire about the rocochlear involvement. Vectoelectronystagmography was presence and clinical characteristics of tinnitus to all new performed when vestibular symptoms were present.
patients at the Otology Clinic of the University Hospi- The patients selected to enter the study then responded to tal, and, during a 6-month period, the authors were able a specific tinnitus questionnaire regarding the following: tin- to identify 500 patients with the symptom. Presbycusis, nitus duration (Ͻ1 year, 1-2 years, 2-5 years, and Ͼ5 years), COM, otosclerosis, Ménière’s disease, noise-induced hear- ear affected (left, right, or both), subjective hearing loss, de-scription of the sound heard (rain, waterfall, whistle, pulsat- ing loss (NIHL), ototoxicity, and acoustic neuroma, in ing noise, click, or other), and known otologic diseases and pre- decreasing order of frequency, were the diagnoses for these vious treatments. The patients were then asked to indicate the patients. However, tinnitus was mild in 81%, moderate intensity of tinnitus on a visual analog scale graded from 1 to in 18%, and severe in only 1% of the patients. Patients 10 (1 was low and 10 was an unbearable level of intensity).
with mild tinnitus did not need treatment, and when Informed consent was obtained from all patients and the symptoms were moderate, they were easily controlled with Ethics Committee for Research Involving Human Individuals drugs such as vestibular suppressants, calcium channel of the Brasília University Medical School gave formal approval blockers, and/or gingko biloba; only 1% needed further of the study protocol. The patients were then randomly as- signed to receive 0.5-mL intratympanic injections of either a Subjective idiopathic tinnitus refers to noise that is 4-mg/mL dexamethasone solution or isotonic sodium chlo-ride (saline) solution (control group). The patients were heard only by the patient. Severe disabling tinnitus (SDT) placed in a supine position on the table with their heads refers to a symptom whose intensity and level of annoy- turned about 45° away from the surgeon. Topical anesthesia ance disrupts the patient’s daily life. Subjective idio- of the tympanic membrane was administered using a gel con- pathic tinnitus can be cochlear or central, ie, have a ret- taining 2.5% lidocaine hydrochloride and 2.5% prilocaine rocochlear origin; subjective idiopathic tinnitus, however, (EMLA; Astra Medical, São Paulo, Brazil). Using a tuberculin always seems to have a central component.
syringe and a 25-gauge needle, the assigned solution was in- Of the 500 patients whom Oliveira et al5 identified as jected under direct vision through an operating microscope at having tinnitus, 1% had SDT. Because compelling evi- the junction of the posterosuperior and posteroinferior quad- dence points to central mechanisms in patients with SDT rants of the tympanic membrane. Each patient remained for even when it originates in the cochlea,6 we reasoned that about 20 minutes in the described position. Four injectionswere performed with the dexamethasone or the saline solu- intratympanic dexamethasone injections should not be
tion, 1 per week for 4 weeks. The solutions were warmed to body temperature before injection to avoid vertigo. If the pa- Taking into consideration that (1) previous studies did tient felt partial improvement of the tinnitus and was willing not use a control group and placebo effect is very high to have another series of injections, another series was done.
with tinnitus; (2) Sakata et al1,2 did not characterize their When there was no improvement at all or when there was a patients as having SDT and their patients were very much good response the treatment was interrupted.
like our 500 patients—of whom only 1% had SDT; and After finishing the treatment, the patients answered a ques- (3) even though Shulman and Goldstein3 characterized tionnaire about the status of their tinnitus (worse, unaltered, their patients as having SDT, they treated only 10 of them slightly improved, greatly improved, and in remission). They and did not use a control group (nor did Cesarani et al,4) also indicated, on the visual analog scale, the level of tinnitusintensity following the treatment. We considered that improve- we decided to undertake a prospective, randomized, ment was significant when a lowering of at least 2 gradations single-blind trial to investigate intratympanic dexameth- on the visual analog scale was reported.
asone injections as a treatment for SDT. We report theresults of this trial.
Five patients who started treatment were excluded fromanalysis (2 from the study group and 3 from the control Starting in June 1997, we developed a protocol to identify pa- group) because they did not complete treatment or failed tients with SDT of probable cochlear origin for whom treat- to return for follow-up. Of the 31 patients who re- ment with drugs had failed. During a 2-year period we se- mained, 4 had both ears treated. Thus, a total of 35 ears lected 36 patients who met the requirements stated in theprotocol.
To ensure that the tinnitus was of cochlear origin, detailed Because only 4 patients had tinnitus in both ears, we anamnesis of the symptom was requested from the patients from refer to the number of ears rather than the number of pa- its inception up to the time of their first visit; otomicroscopic tients. Table 1 gives the otologic diagnosis for the 35
examination and audiologic testing were also performed to iden- ears, with the number and percentage of ears with each tify the presence of otological diseases associated with the symp- diagnosis. Presbycusis was the most prevalent diagno- tom of tinnitus (NIHL, ototoxicity, COM, otosclerosis, sud- sis, followed by NIHL, COM, otosclerosis, Ménière’s dis- den deafness, and Ménière’s disease) and hearing loss.
ease, idiopathic tinnitus (no cause for the symptom was A complete head and neck examination was performed in all found), sudden deafness, and ototoxicity.
patients. Laboratory evaluations included complete blood cell Duration of tinnitus was greater than 5 years in 57% count; serum electrolyte concentrations; serum glucose, choles-terol, and triglyceride levels; and venereal disease research labo- and less than 1 year in only 4% of the ears. Patients graded ratory slide testing. A thyroid hormone test was performed when tinnitus intensity from 5 to 7 on the visual analog scale there was reason to suspect thyroid malfunction. Impedance test- for 48% of the ears and higher than 7 for 51% of the ears.
ing was done in all patients, and brainstem-evoked response au- These results reflect patient selection, as they experi- diometry was also performed when there was a suspicion of ret- (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 131, FEB 2005 Downloaded From: http://archotol.jamanetwork.com/ on 07/04/2012
Medical Association. All rights reserved.
Of the patients who completed both treatment and evaluation, 13 (14 ears) received injections of a normal Table 1. Otologic Diagnosis in 35 Ears Selected
saline solution and 18 (21 ears) received injections of for Treatment
a dexamethasone solution. Follow-up varied from 3 to31 months, with an average of 13.4 months.
Diagnosis
Ears, No. (%)
STUDY GROUP
Table 2 gives the otologic diagnoses in the 21 ears of
the study group. They were similar to the diagnoses for the entire group (35 ears) (Table 1).
Tinnitus intensity as measured on the visual analog scale was from 5 to 7 for 43% of ears and above 7 for 57%of the ears in the study group. These results were simi-lar to those obtained for the entire group. Duration oftinnitus was greater than 5 years in 57%, between 2 and low-frequency hearing loss in 13%. Age in this group var- 5 years in 19% and less than one year in 14%. Hearing ied from 20 to 80 years with a mean age of 55 years, which loss in the high frequencies (4 to 8 kHz) was present in was similar to the age of the patients in the study group.
72% of the ears, 2 ears were anacusic (11%), and 3 ears Table 3 presents the overall results of saline intratym- had normal hearing (17%). The age of the patients in the panic injections regarding tinnitus intensity in the 14 ears study group varied between 30 and 80 years, averaging of the control group. The average score on the visual ana- log scale was 7.57 before the injections and 6.21 after the Table 2 presents the results of the treatment with in- injections, with an average improvement of 1.36.
tratympanic injections of dexamethasone in 21 ears. The Four of the 14 ears showed significant improvement average score on the visual analog scale was 8.04 before (Table 3); NIHL was the otologic diagnosis in 2, COM in treatment and 6.90 after treatment, with an average im- 1, and presbycusis in 1. Age in the control patients with significant improvement varied between 40 and 60 years.
Seven ears in 6 patients had significant improvement Tinnitus intensity was from 5 to 7 in 2 ears and greater than (at least 2 gradations on the visual analog scale) (Table 2).
7 in 2. Tinnitus duration was from 2 to 5 years in 3 ears Three had COM, 2 had NIHL, 1 had otosclerosis, and 1 and less than 2 years in 1 for these patients. Three ears that had Ménière’s disease. Tinnitus intensity was greater than showed tinnitus improvement had high-frequency hear- 7 on the visual analog scale in 3 ears (43%) and 5, 6, or ing loss and 1 had mid-frequency hearing loss.
7 in 4 ears (57%). One ear had mild hearing loss, in the Ten ears in the control group had no improvement.
median frequencies, 5 had high frequency hearing loss The otologic diagnoses for these ears are displayed in and 1 was anacusic. Tinnitus improvement was moder- Table 3 and are not different from the diagnoses for the ate in 5 ears and marked in both ears of the same patient 4 ears that showed improvement, except that there was 1 patient with ototoxicity, 1 with Ménière’s disease, and Fourteen ears in 14 patients did not show any im- 1 with otosclerosis; 1 patient was considered to have id- provement either on the visual analog scale or in pa- iopathic tinnitus. The age of the patients in the control tients’ answers to the questionnaire that they completed group who had no improvement varied from 30 to 80 after treatment. The otologic diagnoses were much like years, with a mean age of 52 years. Tinnitus intensity was those found in the 7 ears that had some improvement, 5, 6, or 7 in 60% of the ears and was greater than 7 in except that there were 3 ears with idiopathic tinnitus in 40%. High-frequency sensorineural hearing loss was pres- the no-improvement group. Nine ears (62%) in the no- ent in 6 ears, 2 ears had mid-frequency hearing loss, and improvement group had tinnitus intensity greater than 1 ear had low-frequency hearing loss. Over time, the study 7, and 5 ears (36%) had a tinnitus intensity of 5, 6, or 7 and control groups both experienced a return to pre- on the visual analog scale. Symptom duration was greater than 5 years in 8 patients (57%), from 2 to 5 years in1 (7%), between 1 and 2 years in 2 (14%), and less than COMPARISON OF THE 2 GROUPS
The ␹2 test (with a significance level of .05) showed no CONTROL GROUP
significant difference between the groups regarding sex,age, tinnitus intensity, and laterality of the tinnitus. There Table 3 gives the otologic diagnoses in the 14 ears of
was no significant difference between the results of treat- the control group. They were similar to those for the en- ment with a dexamethasone solution and treatment with tire group (Table 1) and for the study group (Table 2).
a saline solution (there was a 33% and a 29% improve- Tinnitus intensity on the visual analog scale was 5, 6, or 7 in 8 ears (53%) and greater than 7 in 6 ears (47%).
Two patients in the study group had light vertigo fol- Tinnitus duration was greater than 5 years in 57%, be- lowing the intratympanic injection. Two patients in the tween 2 and 5 years in 21%, and less than 2 years in 21%.
control group had light vertigo, and 1 complained of otal- High-frequency hearing loss was present in 60% of the gia following the injections. These complaints were mild ears, mid-frequency hearing loss was present in 27%, and and resolved spontaneously soon after the injections. No (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 131, FEB 2005 Downloaded From: http://archotol.jamanetwork.com/ on 07/04/2012
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Table 2. Otologic Diagnoses in 21 Ears in the Study Group
VAS Score*
Patient No.
Side of Symptom
Pretreatment†
Posttreatment‡
Complication
Diagnosis
Abbreviations: COM, chronic otitis media; NIHL, noise-induced hearing loss; VAS, visual analog scale.
§Improvement was significant (defined as a lowering of tinnitus by at least 2 gradations on the VAS).
Table 3. Otologic Diagnoses in 14 Ears in the Control Group
VAS Score*
Patient No.
Side of Symptom
Pretreatment†
Posttreatment‡
Complication
Diagnosis
Abbreviations: COM, chronic otitis media; NIHL, noise-induced hearing loss; VAS, visual analog scale.
§Improvement was significant (defined as a lowering of tinnitus by at least 2 gradations on the VAS).
changes in hearing level were noted in either group af- jections in relation to treatment of SDT. Twenty-nine per- cent of the ears in the control group and 33% of those inthe study group had significant improvement of the symp- tom (at least 2 gradations on the visual analog scale).
These findings are not significantly different from each Our results clearly show that there is no difference be- other, and both are similar to the known placebo effect tween dexamethasone and normal saline intratympanic in- of any tinnitus treatment (30%-40%).
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 131, FEB 2005 Downloaded From: http://archotol.jamanetwork.com/ on 07/04/2012
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If we compare our study with the study by Sakata et cal memory for the symptom, so that a final common path- al,2 the differences are very clear, as they treated 1466 way for the sensorial and affective components of SDT ears without selecting those presenting with SDT. In 1999 Oliveira et al5 determined that of 500 patients with the Even though these hypotheses are still unproven, one symptom of tinnitus, and with otologic diagnoses very fact seems clear: SDT always has a central component even similar to those present in the sample of Sakata et al,2 only when of cochlear origin. It is not surprising, then, that 1% had SDT. In 81% of the patients, tinnitus was mild intratympanic injections of dexamethasone or saline so- and did not really bother the patients. In 18% it was mod- lutions are equally inefficient in the treatment of SDT.
erate, perfectly tolerable, and easily controlled with rou- Drug therapies directed to the central nervous system (GABAergics, benzodiazepine, and calcium channel block- Severe disabling tinnitus is different from the more ers), retraining therapy, and masking strategies should common form of tinnitus in several ways. The symptom be more promising avenues in this regard.
is intense, with a high annoyance level and an affectivecomponent that alters the patient’s routine and makeshim or her unable to perform daily tasks efficiently.
Submitted for Publication: November 7, 2004; final re-
Some facts must be considered to understand why SDT vision received September 23, 2004; accepted October is different. In 1989, House6 severed the cochlear nerves of patients with Ménière’s disease who were undergoing Correspondence: Carlos A. Oliveira, MD, PhD, SHIS
vestibular nerve section and who also had severe tinni- QL-22 Conjunto-04 Casa-09, Brasília–DF 71650-145 tus. Considering that tinnitus in Ménière’s disease cer- Brazil ([email protected]).
tainly has a cochlear origin, it was surprising to learn that Previous Presentation: This study was presented in poster
a large percentage of these patients continued to expe- form at the 10th Triennial Meeting of the International rience the unaltered symptom after the cochlear nerve Otopathology Society; June 8-10, 2003; Boston, Mass.
was severed. Somehow, central auditory pathways keptthe symptom of tinnitus alive after cochlear deafferen- tation. A lack of central suppression of spontaneous au-ditory pathways could explain the noise permanence.
1. Sakata E, Itoh A, Ohtsu K, Nakasawa H, Iwashita N. Pathology and treatment of In 1995 Shulman et al7 reported 2 carefully studied cochlear tinnitus by blocking with 4% lidocaine and decadron infusion. Pract Otol(Japan). 1982;75:2525-2535.
cases of SDT who had regional cerebral blood flow ab- 2. Sakata E, Itoh A, Itoh Y. Treatment of cochlear tinnitus with dexamethasone in- normalities detected by single photon emission com- fusion into the tympanic cavity. Int Tinnitus J. 1996;2:129-135.
puted tomography with technetium Tc 99m hexa- 3. Shulman A, Goldstein B. Intratympanic drug therapy with steroids for tinnitus control.
methyl propyleneamine oxide. These abnormalities were Int Tinnitus J. 2000;6:10-20.
4. Cesarani A, Capobianco S, Soi D, Giuliano DA, Alpini D. Intratympanic dexameth- present in the medial temporal lobe region (temporal, pa- asone treatment for control of subjective idiophatic tinnitus: our clinical experience.
rietal, and hippocampal amygdala). Since the patients had Int Tinnitus J. 2002;8:11-113.
no neurological diseases or symptoms, they concluded 5. Oliveira CA, Venosa A, Araújo MF. Tinnitus program at Brasília University Medical that these changes in blood flow were from SDT and hy- School. Int Tinnitus J. 1999;5:141-143.
pothesized the development of a paradoxical memory for 6. House JW. Therapies for tinnitus. Am J Otol. 1989;10:163-165.
7. Shulman A, Strashun AM, Afryie M, Aronson F, Abel W, Goldstein B. SPECT im- SDT in this area of the brain. In addition, the affective aging of brain and tinnitus: neurotologic/neurologic implications. Int Tinnitus J.
component of tinnitus would be related to this paradoxi- (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 131, FEB 2005 Downloaded From: http://archotol.jamanetwork.com/ on 07/04/2012
Medical Association. All rights reserved.

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