Indian J Otolaryngol Head Neck Surg
(January 2014) 66(Suppl 1):S1–S5; DOI 10.1007/s12070-011-0374-8
R EVI EWARTI C LE
Pathophysiology and Treatment of Tinnitus: An Elusive Disease
Alp Atik
Received: 29 April 2011 / Accepted: 15 November 2011 / Published online: 15 December 2011
Association of Otolaryngologists of India 2011
Abstract Tinnitus is a perception of sound in proximity to
the head with the absence of an external source. It is
estimated to occur in 15–20% of the world’s population,
with 1–3% of cases severely affecting quality of life.
Severe tinnitus is frequently associated with depression,
anxiety and insomnia. Tinnitus has been associated with a
variety of risk factors, including prolonged noise exposure,
head and neck injury and infection. The most recent
pathophysiologic theory of tinnitus suggests that the
central nervous system is the source or ‘‘generator’’ of this
con-dition. However, treatment modalities are still aimed
at lessening the awareness of tinnitus and its impact on
quality of life rather than attaining a definitive cure. Cur-
rently, no drug is available that has demonstrated replica-
ble, long-term reduction of tinnitus impact in excess of
placebo effects. However, the market value of such an
agent is estimated to be $1.1 billion, with a potential for
increase with an aging and longer-living population. This
review assesses the current developments in the patho-
physiology and treatment for tinnitus, which remains a
chronic and debilitating condition.
Keywords Tinnitus Pathophysiology Treatment
A. Atik (&)
Department of Head and Neck Surgery, Royal Prince Alfred
Hospital, Camperdown, NSW, Australia e-mail:
alp_atik@hotmail.com
A. Atik
Medical Teaching and Administration Unit, Royal Prince Alfred
Hospital, Missenden Road, Camperdown, NSW 2050, Australia
Introduction
Tinnitus, originating from the Latin word ‘tinnire’ (‘to
ring’), is a perception of sound in proximity to the head
with the absence of an external source [1]. It may be
described as buzzing, ringing, roaring, whistling or hissing
and can be variable and complex. Tinnitus may be inter-
mittent, continuous or pulsatile, with the latter being at best
annoying and often quite distressing. It is estimated that
approximately 15–20% of the world population suffer from
tinnitus [2, 3]. For about 25% of those affected, the con-
dition interferes with daily activity, with 1–3% of cases
severely affecting quality of life [3]. Severe tinnitus is
frequently associated with depression, anxiety and insom-
nia [4, 5].
During the second half of the 20th century, several
theories for the aetiology of tinnitus were proposed and
treatment modalities in the form of medications and sur-
gery were developed with varying degrees of success [6].
Even with these advances, tinnitus continues to be a
debilitating condition with no definitive cure, sometimes
driving the patient to suicide [7].
Classification
Tinnitus can be classified in two categories. Objective
tinnitus is associated with generation of noise near the ear
that, in some cases, can be heard by the examiner using a
stethoscope [8]. Subjective tinnitus is the perception of
sound in the absence of an acoustic stimulus and is heard
only by the patient [8].
Objective tinnitus is an uncommon occurrence involving
an audible, pulsatile hum and can be caused by turbulent flow
through the carotid artery or jugular vein [9]. Highly
123
S2
vascular middle ear tumours (e.g. glomus jugulare
tumours) and dural arteriovenous malformations may also
cause objective tinnitus [10].
Subjective tinnitus is much more common and may
occur with almost any ear disorder [9]. Common causes
include sensorineural hearing loss (e.g. acoustic trauma),
obstruction of the ear canal by cerumen, infections (e.g.
otitis media), Eustachian tube obstruction and drugs such
as salicylates [11]. The majority of patients have ‘‘senso-
rineural’’ tinnitus, which is associated with hearing loss at
the cochlea or cochlear nerve level [12].
Pathophysiology
Tinnitus has been associated with a variety of risk factors,
including prolonged noise exposure (22% of cases), head/
neck injury (17% of cases) and infections (10% of cases)
[13]. The most recent pathophysiologic theory suggests
that the central nervous system is the source or
‘‘generator’’ of tinnitus [14]. Positron emission
tomography (PET) scanning and functional magnetic
resonance imaging (fMRI) studies indicate that a loss of
cochlear input to neurons in the central auditory system
(such as occurs in cochlear hair cell damage or a lesion of
the vestibuloco-chlear nerve) can result in abnormal neural
activity in the auditory cortex [15]. This activity is linked
to the percep-tion of tinnitus. In addition, there is also a
loss of sup-pression of the neural feedback loops which
help tune and reinforce auditory memory in the central
auditory cortex [10]. Disruption of this feedback loop leads
to the disin-hibition of normal synapses and the creation of
uncon-trolled alternative neural synapses which lead to the
abnormal auditory perception of tinnitus (Fig. 1) [16].
Fig. 1 Pathophysiology of tinnitus
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Indian J Otolaryngol Head Neck Surg (January 2014) 66(Suppl 1):S1–S5
Recent improvements in neuro-otometry have confirmed
the complex pathophysiologic mechanisms involved in
tinnitus, elucidating sites in which these processes take place
[17–19]. It is now known that approximately 24% of cases
occur as a result of abnormalities within the otoa-coustic
periphery (i.e. inner ear and the vestibulocochlear nerve), 35%
originate from the acoustic pathways and 41% have their
cause within supratentorial structures [6]. A decrease in
inhibition and/or increase in excitation may lead to an
excitatory-inhibitory imbalance causing neuronal
hyperexcitability in these regions and lead to the perception of
tinnitus [20]. However, neuronal excitability can be
modulated by different neurotransmitters and neuromodu-
lators that act on voltage- or ligand-gated channels, thus
providing potential pharmacologic targets [20].
Treatment
Since tinnitus is associated with marked irritability, agita-
tion, stress, depression, insomnia and interference with
daily life, even a drug that produces a small but significant
effect would have a significant therapeutic impact. How-
ever, due to the myriad of aetiologies and complex path-
ogenic mechanisms proposed, definitive treatment for
tinnitus is yet to be developed. There is currently no single
Food and Drug Administration (FDA) or European Medi-
cines Agency (EMEA) approved drug in the market. No
studied drug in the literature provides replicable, long-term
reduction of tinnitus impact in excess of placebo effects
[21, 22]. Current treatment strategy is aimed at controlling
underlying disorders and symptomatically suppressing the
perception of tinnitus. The primary goal has thus been
improvement in quality of life rather than absolute cure.
This may be achieved through a variety of regimens,
though none show complete efficacy.
Comprehensive management of tinnitus includes
assessment of hypertension, blood lipids, thyroid function,
allergies and informing patients of factors that aggravate
tinnitus, such as stress, caffeine, nicotine, and aspirin [21].
Treatment of comorbidities may involve procedures such
as embolization or ligation for vascular abnormalities such
as arteriovenous malformations. Hearing aids for presby-
cusis, cochlear implants for sensorineural hearing loss and
cessation of any offending medications are also important
components of management [23].
Many patients with tinnitus exhibit signs of anxiety or
depression, associated with elevated serum serotonin levels
[24]. Serotonin and GABA receptors are found throughout
the auditory system, and neurotransmitter abnormalities
have been purported to play a role in some patients [25,
26]. Attempts at symptomatic relief have included
antidepressants (e.g. amitriptyline) [27], anxiolytics (e.g.
Indian J Otolaryngol Head Neck Surg (January 2014) 66(Suppl 1):S1–S5
diazepam), anticonvulsants (e.g. clonazepam), diuretics,
and antihistamines (e.g. dexchlorpheniramine maleate), all
of which have yielded inconsistent and inconclusive results
[28].
Tinnitus-specific medications have also proven ineffec-
tive. Trials of the prostaglandin E1 analogue misoprostol
[29], gabapentin [30], lidocaine [31] and dexamethasone
[32] have only shown limited benefit. Complementary and
alternative medicine (CAM) therapies are equally disap-
pointing. Large trials of Ginkgo biloba, the most popular
form of CAM therapy, have failed to yield definitive
results [33].
In contrast, a number of non-medical treatments have
been studied with some success. These include tinnitus
retraining therapy (TRT), masking, biofeedback and cog-
nitive behavioral therapy.
TRT is based on bypassing or overriding abnormal
auditory cortex neural connections—the pathogenic
mechanism postulated to drive tinnitus. It is based on the
principle that all levels of the auditory pathways play
essential roles in tinnitus, and induces habituation to the
tinnitus signal [34]. The goal is to reach a stage in which
patients are unaware of their condition unless they con-
sciously focus on it. This habituation is achieved by
directive counseling, combined with low-level noise gen-
erated by wearable generators and environmental sounds.
Significant improvement has been reported in up to 80% of
patients but well-controlled studies are not reported, the
long-term impact is not known, and the therapy takes at
least one to 2 years before effects are seen [35].
Masking devices are designed to produce low-level
sounds that reduce the perception of tinnitus. It is not
successful in all patients and some patients have even
reported a worsening of their tinnitus [35].
Biofeedback is a relaxation technique teaching people to
control certain autonomic body functions. The goal is to
help people manage tinnitus-related distress by changing
the patient’s reaction to it. Many people have noticed a
reduction in tinnitus when they are able to modify their
reaction to it [36], though well-controlled trials have not
yet been completed.
Cognitive behavioral therapy aims to motivate patients
to learn to alter their psychological response to tinnitus by
identifying and reinforcing coping strategies, distraction
skills and relaxation techniques. Several studies have
shown benefit compared to control patients in reducing
tinnitus-related distress, but no benefit on the loudness of
the tinnitus [36].
It is now recognized that every patient with tinnitus has a
unique medical, psychological and social experience. A
number of recent studies recommend individualized man-
agement programs utilizing multimodal strategies designed to
address the specific needs of each patient [11, 27, 35, 36].
S3
These studies have suggested that a tinnitus management
team, comprising of an otolaryngologist, audiologist, neu-
rologist, psychologist and sleep or pain specialists, is
essential for the successful treatment of tinnitus.
Future Therapy
Although there are no current FDA or EMEA approved
drugs to treat tinnitus, a potential market appears to be
emerging. The Royal National Institute of Deafness in the
United Kingdom estimated the patient opportunity for a
tinnitus drug would be 15 million by 2012. The market
value of tinnitus retraining therapy and off-label pharma-
ceuticals was estimated in 2003 to be $127 million. The
market value of the whole segment ‘symptomatic relief
from tinnitus’ was estimated to be $1.1 billion, with a
potential for increase if an effective drug is to become
available. This is because there is a significant number of
people with tinnitus who have stopped seeking medical
treatment due to lack of efficacy, but who would probably
be interested in treatment as soon as an effective
compound is made available [37].
Currently, there are only a small number of drugs in
development for the treatment of tinnitus. One of these is
neramexane, a non-competitive, voltage-dependent NMDA
antagonist which also blocks nicotinic cholinergic recep-
tors expressed on hair cells in the inner ear [38–40]. After
promising Phase 2 trial results, the drug is currently in
Phase III multi-centre clinical trials to determine its effi-
cacy, safety and tolerability.
LidoPAIN TV is a non-sterile patch delivering lido-
caine, which is applied to the periauricular skin region.
According to the company, it has demonstrated efficacy in
a clinical proof-of-concept study and has been in Phase II
trials for tinnitus.
Vesitipitant is a novel antagonist of the neurkinin-1
receptor which binds substance P. Neurokinin receptors are
present in the inner ear, representing a potential therapeutic
target for tinnitus [41]. Vestipitant and the combination of
vestipitant and paroxetine are currently undergoing Phase 2
clinical trials for the treatment of tinnitus.
Conclusion
Tinnitus may originate in any location along the auditory
pathway from the cochlear nucleus to the auditory cortex.
Some leading theories include injured cochlear hair cells
which repetitively stimulate auditory nerve fibers, sponta-
neous activity in individual auditory nerve fibers, hyper-
activity of auditory nuclei in the brain stem or a reduction
123
S4
in the usually suppressive activity of the central auditory
cortex on peripheral auditory nerve activity.
Though there have been advances in the understanding of
the pathophysiology of this condition, the treatment modal-
ities are still aimed at lessening the awareness of tinnitus and
its impact on quality of life rather than attaining a definitive
cure. Currently, no drug is available that has demonstrated
replicable, long-term reduction of tinnitus impact in excess of
placebo effects. Medical therapy has been limited in efficacy
and consistency and more research needs to be conducted into
non-medical treatment modalities such as TRT, cognitive
behavioral therapy and masking. As a result, tinnitus remains
a chronic, often debilitating condition for a significant number
of patients. However, the development of molecular,
biochemical and imaging techniques are offering increasing
insights into the underlying causes of tinnitus and for the
development of new potential targets for treatment.
Acknowledgments I accept to undertake all the responsibility for
authorship during the submission and review stages of the manuscript. No
financial support was received in the preparation of this article.
Conflict of interest The authors declare that they have no conflict of
interest.
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 Patofisiologi dan Pengobatan Tinnitus: Penyakit yang Sulit Dipahami

Abstrak
Tinnitus adalah persepsi suara yang terasa dekat dengan kepala, namun tidak memiliki sumber
eksternal. Hal ini diperkirakan terjadi pada 15-20% populasi dunia, dengan 1-3% kasus sangat
mempengaruhi kualitas hidup. Tinnitus berat sering dikaitkan dengan depresi, kecemasan dan
insomnia. Tinnitus dikaitkan dengan berbagai faktor risiko, termasuk paparan bising yang
berkepanjangan, cedera kepala dan leher, dan infeksi. Teori terbaru patofisiologi tinnitus
menunjukkan bahwa pusat sistem saraf adalah sumber atau pencetus dari kondisi ini. Namun,
modalitas pengobatan masih ditujukan untuk mengurangi kesadaran akan tinnitus dan dampaknya
terhadap kualitas hidup, daripada mencapai penyembuhan pasti. Saat ini, tidak ada obat yang tersedia
yang telah dibuktikan secara berulang, yang menunjukkan pengurangan dampak tinnitus jangka
panjang lebih dari efek plasebo. Namun, nilai pasar seperti modalitas pengobatan tersebut
diperkirakan $1,1 miliar, dengan potensi meningkat pada populasi lansia. Ulasan ini menilai
perkembangan terkini dalam patofisiologi dan pengobatan untuk tinnitus dengan kondisi kronis.

Pendahuluan
Tinnitus, berasal dari kata Latin 'tinnire' ('berdenging'), adalah persepsi suara yang terasa dekat
dengan kepala, namun tidak memiliki sumber eksternal. Persepsi tersebut digambarkan seperti
berdengung, berdenging, menderu, bersiul atau mendesis dan dapat bervariabel dan kompleks.
Tinnitus dapat hilang timbul, terus menerus, atau berdenyut, sehingga akan sangat menggangu dan
dapat menyebabkan stres. Diperkirakan sekitar 15-20% populasi dunia menderita tinnitus. Sekitar
25% dari mereka yang mengalami tinnitus, memiliki kondisi yang mengganggu aktivitas sehari-hari,
dengan 1-3% kasus sangat mempengaruhi kualitas hidup. Tinnitus berat sering dikaitkan dengan
depresi, kegelisahan dan insomnia.
Selama paruh kedua abad ke-20, diusulkan beberapa teori untuk etiologi dan modalitas
pengobatan berupa obat dan pembedahan dikembangkan dengan berbagai tingkat keberhasilan.
Bahkan dengan kemajuan ini, tinnitus terus menjadi kondisi yang melemahkan tanpa penyembuhan
pasti, terkadang mendorong pasien untuk bunuh diri.
Klasifikasi
Tinnitus dapat diklasifikasikan dalam dua kategori. Tinnitus obyektif dikaitkan dengan
munculnya suara bising di dekat telinga, dalam beberapa kasus, bisa didengar oleh pemeriksa dengan
menggunakan stetoskop. Tinnitus subyektif adalah persepsi suara, namun tidak terdapat rangsangan
akustik dan hanya terdengar oleh pasien.
Tinnitus obyektif adalah kejadian yang jarang terjadi, meliputi dengungan yang terdengar dan
berdenyut dan bisa disebabkan oleh suara aliran dari arteri karotis atau vena jugularis. Tumor telinga
tengah dengan vaskularisasi yang banyak (misalnya: tumor glomus jugulare) dan malformasi
arteriovenosa dural dapat juga menyebabkan tinnitus obyektif.
Tinnitus subyektif jauh lebih umum dan mungkin terjadi pada hampir semua gangguan telinga.
Penyebab umum adalah tuli sensorineural (misalnya trauma akustik), obstruksi saluran telinga oleh
serumen, infeksi (misalnya: otitis media), obstruksi tuba Eustachius, dan efek obat seperti salisilat.
Mayoritas pasien memiliki tinnitus 'sensorineural', yang berhubungan dengan gangguan pendengaran
pada koklea atau permukaan saraf koklea.

Patofisiologi
Tinnitus dikaitkan dengan berbagai faktor risiko, meliputi paparan bising yang berkepanjangan
(22% kasus), cedera kepala/leher (17% kasus) dan infeksi (10% kasus). Teori patofisiologis terbaru
menunjukkan bahwa sistem saraf pusat adalah sumber atau pencetus dari tinnitus. Positron emission
tomography (PET), scanning, dan functional magnetic resonance imaging (fMRI) menunjukkan
bahwa hilangnya input dari koklea ke neuron di sistem pendengaran utama (seperti yang terjadi di
kerusakan sel rambut koklea atau lesi saraf vestibulokoklear) dapat menyebabkan aktivitas saraf
abnormal pada korteks pendengaran. Aktivitas ini terkait dengan persepsi dari tinnitus. Selain itu,
hilangnya tekanan dari umpan balik saraf yang membantu menyesuaikan dan memperkuat memori
pendengaran di korteks auditori sentral. Gangguan umpan balik ini menyebabkan hilangnya inhibisi
sinaps normal dan terbentuknya sinapsis neural alternatif yang tidak terkendali yang mengarah pada
persepsi pendengaran yang tidak normal tentang tinnitus (Gambar 1).
 Perkembangan terbaru pada neuro-otometri telah memastikan mekanisme kompleks
patofisiologis tinnitus, menjelaskan bagaimana proses terjadinya. Sekarang diketahui bahwa sekitar
24% kasus terjadi akibat kelainan pada perifer otoakustik (yaitu telinga bagian dalam dan saraf
vestibulokoklear), 35% berasal dari jalur akustik dan 41% memiliki penyebabnya dalam struktur
supratentorial. Penurunan inhibisi dan/atau peningkatan rangsangan menyebabkan ketidakseimbangan
hambat-rangsang sehingga terjadi hipereksitabilitas neural dan mengarah pada persepsi tinnitus.
Namun, rangsangan neuronal dapat dimodulasi oleh neurotransmitter dan neuromodulator yang
berbeda yang bertindak pada saluran tegangan atau ligan, sehingga memberikan target farmakologis
potensial.

Pengobatan
Karena tinnitus dikaitkan dengan iritabilitas, agitasi, stres, depresi, insomnia dan gangguan
kehidupan sehari-hari, bahkan obat yang menghasilkan efek kecil tapi signifikan akan memiliki
dampak terapeutik yang signifikan. Namun, karena banyaknya usulan etiologi dan patogen
mekanisme yang kompleks, pengobatan definitif untuk tinnitus belum dikembangkan. Saat ini tidak
ada persetjuan dari Food and Drug Administration (FDA) atau
European Medicines Agency (EMEA) untuk memasarkan obat. Tidak ada obat dalam literatur bisa
direplikasi, reduksi dampak jangka panjang tinnitus lebih dari efek plasebo. Strategi pengobatan saat
ini bertujuan untuk mengendalikan gangguan dasar dan secara simtomatik menekan persepsi tinnitus.
Tujuan utamanya adalah meningkatkan kualitas hidup daripada penyembuhan mutlak. Hal ini dapat
dicapai melalui berbagai cara hidup, meski tidak ada yang menunjukkan khasiat yang sempurna.
Manajemen tinnitus yang komprehensif mencakup penilaian hipertensi, lipid darah, fungsi
tiroid, alergi dan menginformasikan pasien faktor yang memperburuk tinnitus, seperti stres, kafein,
nikotin, dan aspirin. Pengobatan komorbiditas mungkin melibatkan prosedur seperti sebagai
embolisasi atau ligasi untuk kelainan pembuluh darah seperti malformasi arteriovenosa. Alat bantu
pendengaran untuk presbycusis, implan koklea untuk tuli sensorineural dan penghentian setiap obat
yang memperberat, juga merupakan komponen penting dalam terapi.
Banyak pasien dengan tinnitus menunjukkan tanda-tanda kegelisahan atau depresi,
berhubungan dengan peningkatan serum serum serotonin. Reseptor serotonin dan GABA ditemukan
di seluruh sistem pendengaran, dan kelainan neurotransmitter telah diakui berperan dalam beberapa
pasien. Upaya untuk menghilangkan gejala dapat menggunakan antidepressant, amitrptyline,
anxiolytics (diazepam), antikonvulsan (misalnya clonazepam), diuretik, dan antihistamin (misalnya
dexchlorpheniramine maleate), semuanya menghasilkan hasil yang tidak konsisten dan tidak
meyakinkan.
Obat spesifik tinnitus juga terbukti tidak efektif. Uji coba misoprostol analog prostaglandin
E1, gabapentin, lidokain, dan deksametason hanya menunjukkan manfaat terbatas. Complementary
Alternative Medicine (CAM) sama mengecewakannya. Percobaan besar Ginkgo biloba, yang bentuk
terapi CAM paling populer, menunjukkan hasil yang tidak pasti.
Sebaliknya, sejumlah perawatan non-medis telah dipelajari dengan beberapa keberhasilan. Ini
termasuk Tinnitus Retraining Therapy (TRT), penggunaan masker, terapi umpan balik dan perilaku
kognitif.
TRT didasarkan pada perjalanan abnormal koneksi saraf korteks pendengaran - dimana
mekanisme patogenik dipostulasikan untuk menjadi tinnitus. Hal ini didasarkan pada prinsip bahwa
semua tingkat jalur pendengaran memiliki peran penting dalam tinnitus, dan menyebabkan habituasi
terhadap sinyal tinnitus. Tujuannya adalah untuk mencapai tahap dimana pasien tidak sadar akan
kondisi mereka kecuali mereka secara sadar fokus pada hal tersebut. Habituasi ini didapatkan dengan
oleh konseling langsung, dikombinasikan dengan bising tingkat rendah yang dihasilkan oleh generator
yang dapat dipakai dan suara lingkungan. Perbaikan signifikan telah dilaporkan mencapai 80% dari
pasien namun studi yang terkontrol dengan baik tidak dilaporkan, dampak jangka panjang tidak
diketahui, dan terapinya memakan waktu paling sedikit satu sampai 2 tahun sebelum efek terlihat.
Penggunaan masker dirancang untuk menghasilkan tingkat rendah suara yang mengurangi
persepsi tinnitus. Hal ini tidak berhasil pada semua pasien dan beberapa pasien bahkan melaporkan
memburuknya tinnitus mereka.
Biofeedback adalah teknik relaksasi untuk mengajar orang mengontrol fungsi otonom tubuh
tertentu. Tujuannya adalah untuk membantu orang mengelola distres terkait tinnitus dengan mengubah
reaksi pasien terhadap hal tersebut. Banyak orang mengalami pengurangan tinnitus saat mereka bisa
memodifikasi reaksi, meskipun uji coba terkontrol dengan baik belum selesai.
Terapi perilaku kognitif bertujuan untuk memotivasi pasien untuk belajar mengubah respons
psikologis mereka terhadap tinnitus dengan mengidentifikasi dan memperkuat strategi koping,
gangguan keterampilan, dan teknik relaksasi. Beberapa penelitian menunjukkan manfaatnya
dibandingkan dengan kontrol pasien dalam mengurangi gangguan terkait tinnitus, tapi tidak ada
manfaatnya pada kerasnya tinnitus.
Sekarang diketahui bahwa setiap pasien dengan tinnitus memiliki pengalaman medis,
psikologis dan sosial yang unik. Sejumlah studi terbaru merekomendasikan manajemen individual
program yang menggunakan strategi multimodal yang dirancang untuk memenuhi kebutuhan spesifik
setiap pasien.
Studi ini menyarankan bahwa tim manajemen tinnitus, terdiri dari otolaryngologist,
audiologist, neurologist, psikolog dan spesialis tidur atau nyeri, yang berguna untuk keberhasilan
pengobatan tinnitus.

Terapi di Masa Akan Datang

Meski saat ini tidak ada FDA atau EMEA yang menyetujui obat untuk mengobati tinitus,
namun pasar potensial akan muncul. The Royal National Institute of Deafness di Inggris
memperkirakan kesempatan pasien untuk obat tinnitus akan menjadi 15 juta pada tahun 2012. Pasar
nilai TRT dan famasi non-label diperkirakan pada tahun 2003 menjadi $ 127 juta. Nilai pasar dari
keseluruhan segmen “gejala dari tinnitus” diperkirakan mencapai $ 1,1 miliar, dengan berpotensi
meningkat jika obat yang efektif tersedia. Hal ini karena ada sejumlah besar orang-orang dengan
tinnitus yang telah berhenti mencari perawatan medis karena manfaat yang kurang, tapi mungkin
tertarik pada pengobatan segera setelah senyawa yang efektif tersedia.
Saat ini, hanya ada sejumlah kecil obat yang dikembangkan dalam pengobatan tinnitus. Salah
satunya adalah neramexane, NMDA yang tidak kompetitif, bergantung tegangan antagonis yang juga
menghambat reseptor kolinergik nikotinik yang berada di sel rambut telinga bagian dalam. Setelah
hasil percobaan fase 2 yang menjanjikan, obat saat ini masuk uji coba fase klinis tahap tiga untuk
menentukan keampuhannya, keamanan dan tolerabilitas.
LidoPAIN TV adalah tampalan kecil non-steril yang berisi lidocaine, yang diaplikasikan pada
daerah kulit periaurikular. Menurut perusahaan, telah menunjukkan kemajuan di sebuah studi klinis
proof-of-concept dan telah di tahap kedua percobaan untuk tinnitus.
Vesitipitant adalah antagonis baru reseptor neurkinin-1 yang mengikat zat P. Reseptor
neurokinin hadir di telinga bagian dalam, menunjukkan target potensi terapeutik untuk tinnitus.
Vestipitant dan kombinasi dari vestipitant dan paroxetine saat ini sedang menjalani fase 2 uji klinis
untuk pengobatan tinnitus.

Kesimpulan
Tinnitus mungkin berasal dari lokasi manapun sepanjang jalur pendengaran dari inti koklea ke
korteks pendengaran. Beberapa teori terkemuka termasuk sel rambut koklea yang terluka yang secara
berulang merangsang serabut saraf pendengaran, aktivitas spontan pada serabut saraf pendengaran
individu, hiperaktivitas pada nukleus pendengaran di batang otak, atau pengurangan dalam aktivitas
yang menekan pusat korteks pendengaran pada aktivitas saraf auditori perifer.
Meskipun sudah ada kemajuan dalam pemahaman patofisiologi kondisi ini, modalitas
pengobatan masih bertujuan mengurangi kesadaran akan tinnitus dan dampaknya terhadap kualitas
hidup daripada mencapai yang penyembuhan definitif. Saat ini, tidak ada obat yang tersedia yang
telah dibuktikan secara berulang, yang menunjukkan pengurangan dampak tinnitus jangka panjang
lebih dari efek plasebo. Terapi medis terbatas pada khasiat dan konsistensi dan penelitian lebih banyak
perlu dilakukan terhadap modalitas pengobatan non-medis seperti TRT, terapi perilaku kognitif dan
masking. Sebagai hasil, tinnitus dengan kondisi kronis dan sering melemahkan terdapat di sejumlah
pasien yang signifikan. Namun, perkembangan teknik molekuler, biokimia, dan teknik pencitraan
meningkatkan wawasan tentang penyebab utama tinnitus dan untuk pengembangan target potensial
baru untuk perawatan.