9Other Drugs and Intratympanic Therapy

FBetahistine and vasodilators

Betahistine, a histamine analogue used for Meniere’s vertigo, is often prescribed for tinnitus on the assumption that improving inner-ear blood flow will quieten the sound. The Cochrane review by Wegner and colleagues tested this and found no good evidence that betahistine helps tinnitus, with side effects no different from placebo [2018].

The same logic underlies older vasodilators and rheological agents, and the same disappointment follows: the ‘poor circulation’ model of chronic subjective tinnitus is largely unsupported, and these drugs are not recommended for it [2014].

TTargeting glutamate: NMDA antagonists and the AM-101 trials

A more mechanistic line of attack targets glutamate excitotoxicity at the synapse between inner hair cells and auditory-nerve fibres, thought to drive aberrant firing in acute, cochlear-origin tinnitus. AM-101 (esketamine, an NMDA-receptor antagonist) was developed for intratympanic delivery to act locally on this synapse [2013].

An early phase II study suggested a signal in acute tinnitus [2014], but the larger confirmatory programme did not establish efficacy, and the drug has not entered practice. It is a clean illustration of a recurring pattern: promising mechanism, early hope, negative confirmation. Systemic NMDA antagonists such as memantine and acamprosate have likewise failed to show convincing benefit [2013].

TIntratympanic steroids and lidocaine

Delivering drug straight to the round window is attractive because it concentrates the agent at the cochlea while sparing the body. Intratympanic corticosteroids are established for sudden sensorineural hearing loss, and are sometimes given hoping to ease accompanying tinnitus — but for chronic isolated tinnitus the evidence of benefit on the percept is weak.

Intratympanic and intravenous lidocaine can transiently abolish tinnitus, a fascinating proof that the percept is modifiable, but the effect is brief and the systemic route risks arrhythmia, so it is not a practical treatment. A recent randomised study of topical intra-auricular lidocaine again showed only limited, short-lived effect [2025]. Across intratympanic approaches, the honest summary is short-lived or unproven benefit for the chronic percept.

CMelatonin for sleep, not for silence

Melatonin is the one agent here with a defensible everyday role — but for sleep, not for the sound. Disturbed sleep is one of the most disabling consequences of tinnitus, and melatonin can improve sleep quality in tinnitus patients with relatively few side effects [2015].

Note the framing carefully: melatonin is treating the insomnia that tinnitus causes, and any reported easing of tinnitus is most plausibly downstream of better sleep and reduced fatigue. As with antidepressants, the principle holds — treat the treatable consequence honestly, and do not promise the patient that any of these drugs will switch the sound off, because the guideline-level evidence simply is not there [2014].