Active substances: Hydroxyzine
On the one hand dopamine is an inhibitory transmitter in the cochlea; on the other hand antidopaminergic drugs improve thalamic filtering of sensory signals.
Sulpiride, an antipsychotic drug that selectively blocks dopamine D 2 receptors 113 significantly reduced subjective ratings of tinnitus and tinnitus visual analogue scores in one double-blind, placebo-controlled study. However, the reductions with sulpiride were not significantly lower than those in the placebo group.
Two further studies investigated combinations of sulpiride with melatonin or with hydroxyzine.
Both combinations were significantly more effective in reducing tinnitus visual analogue scale and tinnitus perception scores than placebo 114; 115.
While these results are encouraging the lack of controls leave many questions unanswered. Piribedil was investigated recently in a double-blind placebo-controlled cross-over study.
Other Compounds A large variety of drugs from different pharmacological classes is currently prescribed for tinnitus see Table 1, in spite of the fact that for a large number of them no data from clinical trials is available.
Here we will review only those compounds, for which clinical studies have been performed.
Systemic and intratympanic steroids have been proposed for the treatment of acute tinnitus, especially if it is related to sudden onset of hearing loss 118 — 120.
Although some studies report positive results in subset of patients, the value of steroids in the treatment of idiopathic sudden sensorineural hearing loss remains unclear since the evidence from randomized controlled trials are contradictory in outcome 121.
Ginkgo biloba contains bioactive flavonoids and terpenes with vasoactive and antioxidant properties and has been proposed for the treatment of a wide range of disorders including tinnitus 122.
Even though some studies have suggested beneficial effects of gingko on tinnitus, particularly in patients with short duration symptoms 123; 124, there is a growing body of evidence from large, well controlled, double-blind, placebo-controlled clinical studies clearly indicating that gingko is no more effective in alleviating tinnitus symptoms than placebo 125 — 127.
Melatonin, a naturally occurring circulating hormone, binds to melatonin receptors and plays an important role in regulating circadian rhythms 128; 129. Melatonin is also a potent antioxidant that protects mitochondrial and nuclear DNA 130 and has been suggested to protect against noise- and drug-induced hearing loss 131; 132.
Since sleep disturbances represent a major complaint and complicating factor in tinnitus, melatonin was evaluated as a treatment for tinnitus in three studies. An open label study found statistically significant improvements on ratings of tinnitus severity and sleep quality 133, whereas a double-blind, placebo-controlled cross over study did not demonstrate superiority of melatonin over placebo 134.
A more recent, randomized, placebo-controlled double-blind study found that melatonin in combination with sulpiride reduced subjective ratings of tinnitus and tinnitus loudness more than placebo 114.
Zinc, an essential trace metal plays an important role in numerous biological signaling functions and is widely distributed in the auditory pathway 135; 136.
While positive results have been reported in some patients with hypozincemia, zinc therapy did not result in tinnitus improvement in patients with normal zinc levels in several double-blind, placebo-controlled studies 137 — 140.
Misoprostol is a synthetic prostaglandin E 1 analogue which is primarily used to prevent gastric ulcers induced by non-steroidal anti-inflammatory drugs 141.
Two subsequent double-blind placebo-controlled studies have shown a significant reduction of tinnitus loudness with misoprostol treatment, but no differences in subjective measures of tinnitus severity 143.
Atorvastatin reduces the synthesis of cholesterol by inhibiting HMG-CoA reductase and is used to lower blood cholesterol and prevent vascular events 144.
In a randomized, double-blind placebo-controlled study over 13 months involving elderly patients with elevated cholesterol, atorvastatin failed to slow the progression of age-related hearing loss or to significantly reduce tinnitus 145.
Nimodipine, a calcium antagonist, which crosses the blood-brain barrier and blocks L-type calcium channels 146 is primarily used in the treatment of subarachnoid hemorrhage 147. Pilot studies also suggest beneficial effects in mood disorders 148.