Tinnitus - Emerging treatments | BMJ Best Practice US

Alternative/complementary therapies

Several herbs and supplements, such as Ginkgo biloba, vitamin B complex, zinc, and melatonin, have been claimed to help reduce tinnitus in some patients. These supplements may act as free-radical scavengers, antioxidants, inhibitors of platelet-activating factors, and may have neuroprotective effects.[64] Many of these supplements lack sufficient evidence and rely on patient testimonials.

Ginkgo biloba

Ginkgo biloba extract is used in Europe to treat the early stage of Alzheimer disease, vascular dementia, and tinnitus of vascular origin.[64] Ginkgo biloba (active ingredients flavonoids and terpenoids) has been found to be efficacious for tinnitus modulation in a few reported controlled trials and systematic reviews.[65][66] One review concluded that there was notable clinical efficacy of EGb 761 (the active component of Ginkgo biloba) in both acute and chronic tinnitus.[66] In total, 11 of the trials found a positive benefit of Ginkgo biloba for tinnitus, though the measurement of clinical efficacy was inconsistent between the studies.[66] Another study evaluated 8 randomized placebo controlled trials using EGb 761, and found this Ginkgo preparation to be superior to placebo in the treatment of tinnitus.[67] However, one randomized controlled trial reported no benefits from Ginkgo biloba, although a limitation of this study was that the investigators did not use the active ingredient in Ginkgo and also employed a suboptimal dosing regimen.[68] The use of Ginkgo biloba as treatment for tinnitus remains controversial and one Cochrane review demonstrated no difference in treatment with Ginkgo compared with placebo.[69] Based on current literature, one can tentatively conclude that Ginkgo may have a modest effect on tinnitus but is not effective in every patient. The low risk to benefit ratio suggests a trial with Ginkgo is a reasonable option when treating patients with mild to moderate tinnitus distress.

Vitamin B complex

The B complex vitamins are a family of nutrients that have been grouped together due to the interrelationships in their function within human enzyme systems, as well as their distribution in natural food sources. Deficiency in these vitamins has been implicated in tinnitus.[70] It has been suggested that supplementation may improve the symptoms in those patients noted to have B12 deficiency and tinnitus distress.[71] However, no randomized controlled trials have shown vitamin B12 to be effective in alleviating tinnitus distress or loudness.

Zinc

Zinc is present in all organs and tissues of the body.[72] The content of zinc in the inner ear is quite high in humans and may play a role in inner ear function. A correlation between low zinc levels and tinnitus has been reported, with some studies showing a decrease in tinnitus with supplementation.[73][74] However, other studies showed little correlation between hypozincemia and tinnitus; and no significant improvement in subjective tinnitus using zinc supplements.[75][76]

Melatonin

Melatonin is produced by the pineal gland primarily at night and is ubiquitous in nature. It affects the sleep-wake cycle, as well as mood, and may act as an antioxidant or free-radical scavenger. Low levels of melatonin have been implicated in tinnitus development in older people.[77][78] A few studies have evaluated the effects of melatonin on tinnitus, and those suffering with sleep disturbances tended to do better.[79][80]

Electrical stimulation

Electrical stimulation by direct current was initially tried by Volta; more recently it has shown promising results. Electrical current is applied via externally placed electrodes on the mastoid bone, zygoma, ear lobe, or other appropriate sites, or to the middle and inner ear with implantable devices. Direct stimulation to the brain has also been attempted in animal and human studies; the effect is postulated to be due to alteration in the spontaneous activity of auditory nerves and production of new spontaneous-like activity by this external electrical stimulation.[9][81] This procedure results in suppression of tinnitus without introducing any undesired sounds like those experienced in tinnitus masking. One study demonstrated relief from tinnitus in 53% to 83% of the studied patients.[82] Hearing difficulties in the patient population have not been reported, but the occurrence of an increase in hearing threshold has been documented. A decrease in speech recognition capabilities was also noted.[83] A meta-analysis found that the efficacy of transcranial direct current stimulation (tDCS) could not be confirmed due to the limited number of studies. However, it reported that all included studies found that tDCS significantly improved tinnitus intensity.[84] This treatment may be suitable for all patients and especially for those patients with previous cochlear implantation.

Cochlear implantation

Cochlear implants appear to alleviate tinnitus in up to 80% of users. Studies have shown that these patients frequently experience a decrease in intensity and amplitude of the tinnitus as well as diminishment of annoyance and anxiety due to their condition. Complete resolution of the tinnitus has been reported in some patients.[85] The placement of cochlear implants in patients with tinnitus should be considered in those who have an accompanying bilateral severe-to-profound sensorineural hearing loss.[86]

Transcranial magnetic stimulation (TMS) and repetitive TMS

Transcranial magnetic stimulation (TMS) is the application of strong magnetic fields to cortical tissue. The use of TMS to modulate abnormal cortical excitability in other pathologies has been described, and the application of this technology to tinnitus has been attempted, with mixed results. Most studies have a limited number of subjects with varying degrees of response. One meta-analysis highlights the need for further studies, particularly with respect to stimulation parameters, patient selection, and outcome. Comparison with more conventional treatment methods should also be explored.[12][87][88] A further meta-analysis found that repetitive TMS appears to be relatively safe and well tolerated based on published data.[89] However, the published data lacks systematic reporting of adverse effects of treatment.

Hyperbaric oxygen treatment

Hyperbaric oxygen treatment (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere absolute. The administration of hyperbaric oxygen was first introduced in the 1960s, and its use in the treatment of tinnitus associated with idiopathic sudden sensorineural hearing loss is based on the theory that the etiology of these symptoms is a hypoxic event. The use of HBOT in the treatment of tinnitus has been evaluated based on mean improvement of tinnitus score and relief of tinnitus. While an improvement in tinnitus with the use of HBOT has been proposed, studies are limited in sample size and power and have not demonstrated statistical significance.[90]

Injection of AM101

Emerging evidence suggests that dysregulation of cochlear N-methyl-D-aspartate (NMDA) receptors may underlie aberrant excitation of the auditory nerve, which in turn is perceived as tinnitus. The blocking of these receptors represents a promising therapeutic approach. In a phase 1/2 clinical trial, the safety and local tolerance of intratympanic injections of the NMDA receptor antagonist AM-101 was evaluated for the first time in humans. The results from the double-blind, randomized, placebo-controlled study show that intratympanically injected AM-101 was well tolerated by study participants, and provided the first indications of therapeutic efficacy.[91]

Vagal nerve stimulator-microtransponder

This is a device approved by the Food and Drug Administration for the management of depression and seizure disorder. It is being studied to determine its effects on tinnitus. The initial studies were carried out in an animal model, and they were able to demonstrate brain plasticity in the auditory cortex using vagal nerve stimulation coupled with a specified sound paradigm.[92]