🔉 Did tinnitus loudness improve?
None shown.
AM-101/TACTT2 failed its loudness endpoint; lidocaine's transient suppression lasts minutes and causes vertigo.
Intratympanic drug injections for Tinnitus: What Does the Evidence Show?
Drugs & Pharmacology
Scope of this assessment. This page assesses treatments for tinnitus itself. Sudden hearing loss, with or without tinnitus, is a different and urgent situation: get a medical evaluation right away if your hearing suddenly drops or seems muffled (all at once or over a few days), even if it began several days ago. Some treatments are time-limited, but that is a reason to be seen now, not permission to wait. For sudden sensorineural hearing loss, the 2019 U.S. guideline (AAO-HNSF) lists corticosteroids as an option within 2 weeks of onset and says clinicians should offer intratympanic steroids when recovery is incomplete 2 to 6 weeks after onset. That advice concerns hearing recovery; it is not evidence about tinnitus relief. In the UK, NICE says people with tinnitus and hearing loss that developed suddenly (over 3 days or less) in the past 30 days should be seen within 24 hours. This is not medical advice. Sources: AAO-HNSF sudden hearing loss guideline (2019) · NICE NG155 referral recommendations
Current evidence
Injections through the eardrum keep failing their controlled tests: the experimental drugs did not beat placebo.
Evidence strength: Weak (1/5) · Tier 5 — weak or unsupported · Evidence independence: Primarily sponsor-supported.
Steroids, lidocaine or experimental drugs injected through the eardrum into the middle ear. The two largest placebo-controlled tinnitus programs on this route tested experimental drugs (AM-101 and OTO-313), and both failed. Steroid injections are used for sudden hearing loss, which is a separate indication (see the note above).
Did tinnitus loudness or distress improve?
🧠 Did tinnitus distress improve?
None shown.
OTO-313: placebo beat drug numerically (36% vs 26% TFI responders). TACTT3 (741 randomized per the EU register; the ClinicalTrials.gov record lists 893) failed its TFI endpoint. Positive results come only from small trials without placebo arms.
Loudness means the tinnitus percept itself became quieter (psychoacoustic matching or loudness ratings). Distress means questionnaire scores such as THI/TFI, sleep, anxiety or quality of life improved — the sound may be unchanged. A THI/TFI improvement is never evidence the tinnitus got quieter.
How strong is the evidence?
The best-controlled data in the field are negative: 1/5, Tier 5.
What the studies found 2 tracked
OTO-313 (intratympanic gacyclidine) Phase 2: negative trial
Searchfield GD, et al. · European Archives of Oto-Rhino-Laryngology · 2023 · N=153 · Randomized placebo-controlled Phase 2
FAILED: responders 26% (OTO-313) vs 36% (placebo), p=0.385 — placebo numerically better. Otonomy discontinued the program and subsequently dissolved.
One of the cleanest demonstrations of the ~30–40% placebo response that plagues tinnitus drug trials.
Keyzilen (AM-101) TACTT2 & TACTT3 Phase 3 failures (registry records)
Auris Medical (sponsor) · ClinicalTrials.gov posted results (no peer-reviewed Phase 3 publication exists) · 2018 · N=343 (TACTT2, registry) + 741 randomized (TACTT3; EU register and sponsor; the ClinicalTrials.gov record lists 893) · Randomized placebo-controlled Phase 3 trials (intratympanic esketamine gel)
FAILED. TACTT2 posted results: loudness change 0.80 vs 0.63 placebo (p=0.32); TFI 10.4 vs 9.6 (p=0.63) — both endpoints failed. TACTT3 (NCT02040194; EudraCT 2012-004099-20; 741 randomized — 373 acute, 368 post-acute per the sponsor — while the ClinicalTrials.gov record lists 893) also missed its primary endpoint (TFI change, baseline to Day 84): the EU Clinical Trials Register results (first posted 4 October 2019) show least-squares mean changes of 10.95 with AM-101 vs 12.44 with placebo in the main stratum (p=0.42); no journal publication was found. Sponsor exited otology (now Altamira Therapeutics).
Failed on both a loudness construct and a distress construct. That no Phase 3 results were ever peer-review published is itself informative.
What are the limitations?
- Both large placebo-controlled programs failed
- 30–40% placebo responder rates explain the open-label 'wins'
Has the result been independently replicated?
None yet. Positive early signals not reproduced; Phase 3 program failed.
What should patients know about safety?
Safety evidence: Limited. Eardrum perforation risk, pain, transient vertigo (especially lidocaine).
Is it available?
Regulatory status: Off-label (steroids); investigational (others). AAO-HNSF 2014 recommends against routine intratympanic drugs for tinnitus.
Availability: Offered off-label by some ENTs · Europe: Same · Cost (approx.): $300–1,500/injection
Related treatments 4
- SPI-1005 (ebselen) — The most advanced drug with a tinnitus-relevant claim — but its trials are in Meniere's disease, and the…
- TRTL-913 (GABA-A modulator) — A new $106M bet that a GABA-A drug can quiet tinnitus — Phase 2 starts soon; no human tinnitus data yet.
- Off-label oral drugs (antidepressants, benzodiazepines, gabapentin, betahistine) — No drug has an FDA-approved indication for tinnitus — and the systematic reviews say none of the usual…
- Supplements (ginkgo, zinc, melatonin…) — Heavily marketed, repeatedly tested — and rigorous reviews have found no reliable benefit.
Evidence last reviewed: 2026-09-04 · Evidence included through: 2026-09-04 · Confidence: high. Open the interactive evidence profile · How we rate evidence.
This page summarizes published research for education. It is not medical advice; it cannot say what will work for any individual. Discuss treatment decisions with a qualified clinician.