There are currently no drugs approved for treatment of tinnitus. The drugs listed below are in various stages of experimental testing.
Lidocaine The earliest treatment ever discovered was lidocaine (Xylocaine), which effectively suppresses tinnitus. Lidocaine is a local anesthetic which acts by blocking voltage-gated sodium channels in neurons, preventing neuronal transmission. Since it is only short-acting (hours) and must be injected by a physician, it is not considered to be useful as a treatment. High doses of lidocaine can also cause tinnitus. Intradermal lidocaine is a possibility, but it has not been studied thoroughly.
Glycine receptor agonists For tinnitus that is caused by overexcitation of the cochlear nucleus, it may be possible to develop glycine receptor agonists. These drugs would mimic the natural neurotransmitter glycine, and re-balance the excitation / inhibition pathways. Thus, the future for tinnitus sufferers is not as gloomy as is commonly believed. Research into glycine receptor agonists is underway.
An interesting fact is that the poisonous alkaloid strychnine is a glycine receptor antagonist, and acts by blocking the glycine receptor; thus, glycine receptor agonists might also be beneficial as a treatment for strychnine poisoning.
GABA-A receptor agonists GABA is another inhibitory neurotransmitter, similar to glycine. A class of drugs called benzodiazepines already exists. These drugs are GABA-A receptor agonists, and might be expected to work on tinnitus by activating the inhibitory limb of the neural network. Some researchers have reported moderate success in treating tinnitus with GABA agonists such as baclofen, clonazepam, and diazepam. However, these drugs are also tranquilizers, and cause undesirable CNS side effects. If the current theory about tinnitus being generated in the brainstem is correct, topical application of these drugs is not likely to work, because the drug would be unable to reach the brainstem. Thus, a systemic drug that is targeted to the brainstem is needed.
There is one report that a high dose of taurine, a partial agonist of glycine and GABA receptors, attenutates tinnitus in rats by decreasing noise in the auditory pathway [38].
Midazolam One report out of Germany reported partial protection by midazolam, another benzodiazepine with GABA(A) modulating properties that is used as a sedative and anticonvulsant. Midazolam was given to rats experiencing salicylate-induced tinnitus [39], which is a commonly used experimental model for tinnitus. Benzodiazepines can cause anterograde amnesia and long-lasting memory problems.
Anticonvulsants Because of the parallels between tinnitus and epilepsy (both of which result from overexcitation of neurons), low doses of anticonvulsants such as gabapentin and carbamazepine have been tried, but with little success so far. Although gabapentin acts on the GABA pathway, it is not a direct GABA agonist; it is believed to work by activating glutamic acid decarboxylase, the enzyme that converts glutamate to GABA. It therefore acts by causing the cell to produce more of the inhibitory neurotransmitter GABA.
Acamprosate Acamprosate, a drug used to treat alcoholism, acts as a glutamate antagonist and GABA agonist. It acts by increasing the number of GABA reuptake sites and increasing GABA transmission. One Brazilian group reported a modest but statistically significant benefit using acamprosate to treat tinnitus.
NMDA antagonists A class of drugs known as NMDA receptor antagonists has been shown to block salicylate-induced tinnitus in animals. These drugs interfere with the excitatory neurotransmitter glutamate. However, salicylate may produce tinnitus by a different mechanism than normal tinnitus, so NMDA antagonists may not be effective in patients. Since glutamate is the predominant neurotransmitter in the brain, these drugs would also act as general tranquilizers or anesthetics. Also, some NMDA antagonists are potent neurotoxins. NMDA antagonists such as caroverine have had moderate success, but unfortunately this class of drugs has very significant side effects, such as psychosis. The anti-Alzheimer drug memantine, and neramexane, which are both NMDA receptor antagonists, are currently being tested.
Neuromuscular-blocking drugs The only neuromuscular blocking drug currently used for tinnitus is botulinum toxin, which has been used to paralyze specific muscles. Other drugs, such as dantrolene, a muscle relaxant used to treat muscle spasticity, and drugs similar to tubocurarine, a powerful quaternary ammonium muscle relaxant, have not been tested. Some antihistamines, such as orphenadrine, which is used to treat muscle spasms, might also be useful. However, there are few reports of these drugs being tested. Injection of botulinum toxin into a muscle will paralyze it for 4-6 months; therefore, injecting it into one of the large muscles needed for chewing or supporting the head would be a very bad idea.
Antidepressants Tricyclic antidepressants such as nortriptyline and serotonin reuptake inhibitors such as paroxetine and sertraline have been reported to reduce tinnitus. These drugs may work because of similarities between tinnitus and neuropathic pain. However, clinical studies have shown conflicting results, with tinnitus sometimes being reduced in depressed patients but not non-depressed patients.
Hyperbaric oxygen The outer hair cells in the organ of Corti facilitate the sensory response of the inner hair cells. The inner hair cells, which are connected to nerve fibers, are the primary sensors for sound. Inner and outer hair cells have no direct blood supply. When a loud sound is heard, they become very active and can deplete their limited supplies of oxygen and their energy molecule, ATP. Thus, it has been hypothesized that hyperbaric oxygen could be beneficial in cases of noise-induced hearing loss and acoustic trauma if it is administered soon enough. However, so far the research has been inconclusive. Beneficial results are sometimes seen if it is administered within the first few months [44]. A similar theory has been proposed for magnesium (see below). If these theories are correct, they would predict that oxygen and magnesium would be most effective within a few hours of a noise trauma, and become much less effective as time goes on.
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