Tinnitus is not a single disease but a group of different diseases with different pathologies and therefore different treatments. Regarding tinnitus as a single disease is hampering progress in understanding of the pathophysiology of tinnitus and perhaps, more importantly, it is a serious obstacle in development of effective treatments for tinnitus. Subjective tinnitus is a phantom sound that takes many different forms and has similarities with chronic neuropathic pain. The pathology may be in the cochlea, in the auditory nerve, or, most commonly, in the brain. Like chronic neuropathic pain tinnitus is not life threatening but influences many normal functions such as sleep and the ability to concentrate on work. Some forms of chronic tinnitus have two components, a (phantom) sound and a component that may best be described as suffering or distress. The pathology of these two components may be different and the treatment that is most effective may be different for these two components. The most common form of treatment of tinnitus is pharmacological agents and behavioral treatment combined with sound therapy. Less common treatments are hypnosis and acupuncture. Various forms of neuromodulation are becoming in use in an attempt to reverse maladaptive plastic changes in the brain.
Sensorineural tinnitus is defined as hearing a sound that has no physical correlate; hence the sound of tinnitus is often described as being a phantom (ghost) sound.
Severe sensorineural tinnitus is a phantom sensation of sound that is often accompanied by an effect that is best described as suffering. In many ways, this form of tinnitus is similar to chronic neuropathic pain [
Many forms of tinnitus have two main attributes. One is the sound the person hears and the other is the general effect the disease has on the person, best described as “distress” or “suffering.” The amplitude (or volume) of the perceived sound and the degree of suffering are not always directly related. The pathology of these emotional components which often accompanies tinnitus is not widely understood and this contributes to the lack of seriousness with which tinnitus is often considered by physicians and other health care personnel.
The pathology of tinnitus is poorly known, but the fact that the disease can occur in people with a severed auditory nerve shows that tinnitus can be caused by abnormal neural activity that is generated in the brain without the involvement of the ear. The phantom sensations in tinnitus and the effects on a person (suffering, distress, etc.) are similar to those of chronic neuropathic pain [
Both chronic neuropathic pain and tinnitus include strong emotional components accompanied by affective “mood” disorders such as depression [
There is a lack of physically visible signs in disorders such as tinnitus and chronic neuropathic pain and there are no objective tests that can assess the strength of the symptoms or determine whether a person indeed has such symptoms. The fact that chronic neuropathic pain or tinnitus is not life threatening contributes to the lack of sympathy from relatives and friends and it lessens concern from physicians and other health professionals. Only the patient’s own description is available in this regard. The patients’ description of his/her tinnitus provides little information about the anatomical location of the pathology.
It has been reported that a little over half of the people who have tinnitus perceive sound as coming from the ear; others perceive the sound as emanating from inside the head. A few people perceive the sound as coming from outside the head. Approximately 60% experience tinnitus bilaterally, while the remainder has unilateral tinnitus [
Almost all people with tinnitus have some form of hearing loss [
If more people who have tinnitus die earlier than people who do not have tinnitus, this would explain the observed decrease in the incidence of tinnitus at advanced age. That would occur if tinnitus has similar risk factors as diseases with high age-related mortality or if comorbidities of tinnitus have high age-related deaths.
The prevalence of tinnitus reported by different epidemiological studies [
The distribution of tinnitus among children has only been the aim of a few studies, but recent research found prevalence among children of 12–19 years to be similar or slightly higher than that of young adults (prevalence of tinnitus was 17.7% in this young population, although only 0.3% of the participants reported severe discomfort caused by tinnitus) [
For some people, tinnitus can be debilitating or unbearable, but for others, it is merely an annoyance. Some people with tinnitus also experience a general effect that is difficult to describe but perhaps is best termed as suffering. Tinnitus that causes suffering has also been described as “bothersome” or “troublesome” tinnitus [
The loudness of the tinnitus sound is often assessed by using an analog scale (e.g., from 1 to 10), but more extensive questionnaires are used to assess the suffering component. The most commonly used questionnaires for assessing the effect of a patient’s tinnitus are the Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, and Tinnitus Reaction Questionnaire [
These questionnaires are supposed to provide a measure of the degree of the handicap based on the loudness of the sound and the degree of annoyance and distress of the tinnitus sound and assessment of its effect on daily activities such as sleep, social interactions, and concentration as well as its effect on emotion and depression. These questionnaires, however, are self-report and the wording of the questions may influence the responses. Dwelling on that matter in the course of formulating an answer to a question may alter a person’s perception of his/her tinnitus. The results must therefore always be evaluated in the context of the clinical impression and the patient’s other tinnitus-related symptoms. This caveat is especially important for judging the effect of treatment. Use of only an analog scale for the loudness of the tinnitus is an incomplete measure of the effect of the treatment. The severity of the distress or suffering must be included in an evaluation of the outcome of treatment and selecting appropriate questionnaires is essential.
The pathology of tinnitus is complex and poorly understood. There is evidence that an interplay exists between peripheral (ear) pathologies and central auditory mechanisms (auditory nervous systems and other parts of the brain) [
Functional imaging methods of various kinds have had limited success in distinguishing between the characteristics of the tinnitus and the anatomical locations of abnormalities. Studies of functional connectivity may have more specific power in distinguishing between different pathologies that can cause tinnitus [
In general, tinnitus research has paid great attention to the role of hyperactivity (increased firing rate) and hyperexcitability in structures of the auditory system. Animal experiments [
The fact that tinnitus can occur without input to the nervous system from the ear is evident from the findings that tinnitus occurs in people who have had their auditory nerve severed. These findings are similar to contemporary hypotheses about the pathology of chronic neuropathic pain [
Many forms of chronic tinnitus may be initiated by abnormalities in the ear or by exposure to loud sounds but, as time progresses, tinnitus tends to become independent of input from the ear. It is now generally accepted that this situation develops through functional changes brought about by activation of neuroplasticity. Neuroplasticity has generally been regarded as beneficial in that it is the basis for learning new skills and recovery from nervous system trauma [
Deprivation of auditory input to the brain is an important promoter of tinnitus through its activation of neuroplasticity. Hearing loss from middle ear problems results in reduced input to the brain from the ear and that may cause tinnitus by activating neuroplasticity. Deprivation of sensory input is the strongest promoter of neural plasticity [
There is now considerable evidence that activation of neuroplasticity is responsible for, or at least contributes to, many forms of tinnitus [
The phantom limb syndrome where pain and other sensations are referred to an amputated limb is a clear example of a condition where it is obvious that the symptoms are generated by functional pathologies in the central nervous system; these symptoms could not have been elicited from the amputated limb to which the symptoms are referred.
The functional changes in the brain that are associated with tinnitus may involve many parts of the brain outside of the traditional auditory structures, such as limbic structure [
Change in temporal integration that occurs in some forms of tinnitus [
An old hypothesis assumes that synchrony (time locking) of neural firing in the auditory nerve is more important in signaling the presence of a sound than an increase in the discharge rate of nerve cells. Consequently, abnormal phase-locking in the auditory structures could cause tinnitus. This hypothesis was later supported by studies by Eggermont and other investigators [
Recent neuroanatomical studies have found that the evidence behind structural abnormalities associated with tinnitus is poor [
Schematic display of the alpha and the gamma network. Connections with a significant group difference were plotted as edges in the networks. The nodes were named as LF (left frontal), RF (right frontal), LT (left temporal), RT (right temporal), LP (left parietal), RP (right parietal), ACC (anterior cingulate cortex), and PCC (posterior cingulate cortex) (modified from Schlee et al., 2009 [
Not only does the functional connectivity in the brain of people who have tinnitus differ from that in people who do not have tinnitus but also the functional connectivity differs between people who have recently acquired tinnitus and people who have experienced tinnitus for a very long time [
Schematic displays of alpha and gamma networks for persons with tinnitus of short and long duration. LF: left frontal, RF: right frontal, LT: left temporal, RT: right temporal, LP: left parietal, RP: right parietal, ACC: anterior cingulate cortex, and PCC: posterior cingulate cortex (modified from Schlee et al., 2009 [
The results of studies of connectivity depend to some extent on which parts of the EEG spectrum are used. Using low frequency (alpha) components as the basis shows different connections compared to using high frequency (gamma waves) as seen in Figure
Tinnitus is one of the three symptoms that define Ménière’s disease. People with vestibular neuroma almost always experience tinnitus. Some body disorders such as temporomandibular joint (TMJ) disorders [
There is evidence that abnormal activation of the dorsal-medial thalamus plays an important role in tinnitus, especially regarding the suffering component. This may explain some of the comorbidities of tinnitus. The subcortical connections from cells in the dorsal-medial thalamus bypass the primary cortices and connect directly to limbic structures such as the amygdala and the hippocampus [
The dorsomedial thalamus may be involved in tinnitus through activation of the nonclassical (extralemniscal) pathways.
There is evidence that stress is involved in creation of tinnitus indicating a role of the sympathetic nervous system. The role of the immune system in tinnitus has received little attention, but studies of its role in chronic neuropathic pain indicate that it may also have a role in tinnitus [
The increased incidence of depression and other affective and psychiatric diseases [
Tinnitus is often accompanied by hyperacusis [
Phonophobia is a rare symptom that may occur together with tinnitus. It involves fear of some kinds of sounds. Misophonia is a strong adverse reaction to very specific sounds, often sounds that are associated with eating [
The term misophonia was introduced by M. Jastreboff and P. Jastreboff, 2001 [
Exploding head is a little known symptom that is characterized by a sensation of sudden, strong sound, often occurring during sleep and waking up a person [
Tinnitus is far more complex than was earlier assumed and many of the treatments now in use are experimental. Some are controversial and some have side effects [
In an attempt to distinguish between tinnitus of different pathologies, much attention has been given to the character of the tinnitus sounds through attempts to match a person’s tinnitus sound to an actual physical sound but that has produced mixed results regarding treatment. The exact character of the tinnitus sound seems to have limited importance in the treatment of the condition, with the possible exceptions of discerning between tonal and atonal tinnitus and determining whether the tinnitus is of low or high frequency. It is possible that the tinnitus sounds do not generally have the character of any physical sound.
Tinnitus is associated with many different treatable disorders. Some forms of tinnitus have underlying somatic disorders and successful treatment of these disorders is often effective in relieving the tinnitus.
When treating people with some forms of tinnitus, it may be beneficial to consider that many people with tinnitus have stress and psychological and psychiatric comorbidities [
Tinnitus often occurs in people who take ototoxic medications such as some antibiotics, diuretics (Furosemide), and cancer drugs (e.g.,
Conductive hearing loss of any kind may be associated with tinnitus and tinnitus is often eliminated or reduced when these problems are resolved. Otosclerosis is often associated with tinnitus, which is relieved when the hearing loss is resolved by a successful operation. Hearing aids can increase the input to the nervous system and oftentimes reduce tinnitus [
Cochlear implants can relieve tinnitus in people who have severe hearing loss [
People with vestibular Schwannoma almost always have tinnitus. Surgical treatment of vestibular Schwannoma rarely reduces or eliminates tinnitus but often exacerbates it. It is nonetheless important to rule out vestibular Schwannoma in all people who have tinnitus that is referred to one ear only and who have asymmetric hearing thresholds. Although vestibular Schwannoma often is the first manifestation in people with NF2, the disorder often has other symptoms that affect other cranial or spinal nerves.
Tinnitus often occurs together with temporomandibular joint (TMJ) problems or neck problems [
There is considerable evidence that stress can promote or exacerbate tinnitus [
Diseases such as hypertension [
Current treatments for idiopathic tinnitus include medication [
Of the above methods, behavioral therapy seems to be the most successful [
The success of treatment of severe tinnitus depends on many factors such as the severity of the tinnitus, its character, and impact on quality of life as well as the patient’s age, hearing status, and whether other diseases are present. Patients’ compliance with treatment regimens is also essential for the success of any treatment. The outcome also depends on a patient’s emotional state and how he or she reacts to the tinnitus.
Behavioral treatments do not depend on knowing the anatomical location of the pathology, but other treatments such as transcranial magnetic stimulation (TMS) or transcranial electrical (DC) stimulation or direct electrical stimulation of specific structures in the brain do.
Many people with tinnitus are convinced, erroneously, that there is something wrong with their ears; the pathologies behind most forms of tinnitus are in the brain. It is important to explain to such patients that altered function in some parts of the brain may imitate the distinctive neural signal of a bona fida sound and that such internally generated neural activity may therefore be interpreted as coming from the ear.
Sometimes the most beneficial treatment is to focus on mitigating the suffering or distress from tinnitus that can affect a person’s daily life rather than trying to decrease the loudness of the tinnitus. The measure of the success of treatment should therefore focus on the entire effect of the tinnitus on a person rather than focusing on the decrease in the perceived tinnitus sound.
It is always important to give the patients realistic hope for success in the treatment. Unfulfilled goals will result in disappointment and search for other health professionals who may promise full relief. Setting a reasonable treatment goal is also important. The absolute goal would be that the distress from the tinnitus and its resulting sound should be eliminated completely. This, however, is not often attainable practically. A more realistic goal would be the reduction of the tinnitus to a level where it is less burdensome (disease management).
Tinnitus has a different effect on different people and different people use widely different ways to describe their tinnitus and their concern. Some people are initially concerned that their tinnitus is a sign of a serious disease such as a brain tumor. Further tests such MRI scans can effectively rule out that possibility and relieve a person from fear of other serious diseases. After a person has been assured that his/her tinnitus is not a sign of a brain tumor, often no treatment is required.
Many different substances have been tried, but few have been both effective and practical to administer and most of the suggested treatments have had more or less severe side effects [
One of the first medications that was shown to suppress tinnitus is the local anesthetic, lidocaine (Xylocaine®), that when injected was shown to suppress tinnitus [
Alprazolam (triazolobenzodiazepine) is a short-acting substance that is used to treat anxiety, panic attacks, and depression. Alprazolam (Xanax®) is a member of the benzodiazepine family that has shown good effect on tinnitus [
Other studies have found that clonazepam on its own does not outperform the placebo until combined with Deanxit® (Flupentixol®) and Melitracen®, an antidepressant [
Some anticonvulsants may have a small beneficial effect on tinnitus [
Some drugs may affect specific aspects of tinnitus. For example, nortriptyline (Aventyl®) that is used to treat people with the chronic fatigue syndrome, migraine, and chronic neuropathic pain [
Zinc and other supplements such as omega 3 have produced positive results in small studies, despite having nonstatistically significant effects in a randomized placebo controlled crossover trial [
Local application of drugs in the ear has had some success in treating tinnitus. Intratympanic dexamethasone is an example that has shown beneficial effect in some persons with tinnitus [
More recently several medications are either under development or advanced to the state of clinical trials. One example is an NMDA-R antagonist, gacyclidine, by the company Otonomy. Gacyclidine is a phencyclidine derivative that has neuroprotective properties. In a study in 6 patients with unilateral deafness and tinnitus it has been shown to provide temporary relief of tinnitus in 4 of 6 patients when administered locally to the cochlea [
Recently the company Sound Pharmaceuticals are testing drugs such as an oral formulation of ebselen [
Particular forms of tinnitus have been treated successfully by microvascular decompression operations [
Several forms of neuromodulation are entering use for the treatment of tinnitus [
Neuromodulation in the form of electrical stimulation of the somatosensory system has been used for many years for treatment of some forms of pain [
It was probably stimulation of parts of the somatosensory system that was the first systematic use of neuromodulation for treatment of tinnitus. It was shown that electrical stimulation of specific peripheral somatosensory nerves can modulate tinnitus in people with some forms of tinnitus. Success with direct stimulation of the surface of the cochlea [
Later it was found that that fibers of the C2 spinal dorsal root that innervate the skin behind the ears also target the cells in the dorsal column nuclei that send axons to cells in the dorsal cochlear nucleus. This is probably the manner in which electrical stimulation of the skin behind the ears suppresses tinnitus [
Acupuncture [
Electrical stimulation of the vagus nerve (vagus nerve stimulation, VNS) is now being studied extensively for treatment of tinnitus and for enhancing reversal of neuroplastic changes that are assumed to have caused a person’s tinnitus [
The vagus nerve is a part of the autonomic nervous system and is involved in the regulation of metabolic homeostasis, playing an important role in the neuroendocrine-immune axis (anti-inflammatory pathway) [
Targets of axons from cells in the nucleus tractus solitarius. Composite of different investigators description of the pathways from the NTS. PGi: Paragigantic nucleus (from Møller, 2014 [
VNS has been used in treatment of some forms of pain [
The vagus nerve also exerts control over the immune system through the vagal immune reflex [
Hypnosis can be regarded as a form of neuromodulation found to be beneficial by some individuals effected by tinnitus. Hypnosis can actually produce functional changes in many parts of the brain. For example, hypnosis can produce general analgesia and it has been found effective in treatment of some forms of pain (see [
Cognitive behavioral therapy (CBT), which aims at treating a person’s reaction to tinnitus, has been shown to be an effective tool in the treatment of many forms of the disease [
Tinnitus retraining therapy (TRT), which can be regarded as a form of behavioral treatment is a well-established treatment of tinnitus that has been reported to have long-term improvement in tinnitus in 80% of patients who were treated [
A person’s reaction to his/her tinnitus has a tremendous impact on the outcome of any treatment. A person can have essentially two different reactions to tinnitus [
Hypothetical description of the difference between catastrophizing and noncatastrophizing in tinnitus (from Møller, 2014 [
A noncatastrophic approach involves confronting the situation, perceiving the issue to be no greater than it actually is.
Catastrophizing statements may induce or reinforce tinnitus. If a person with tinnitus repeatedly hears or reads a statement such as “I cannot sleep because of my tinnitus,” the person may become convinced that his/her insomnia is caused by the tinnitus. Though the insomnia may be caused by another factor, if the tinnitus patient is convinced that the insomnia is linked to the tinnitus, he or she may retain the insomnia even after the actual cause is removed.
Coping is a learned beneficial skill that can reduce suffering [
An examination of the studies of new medications, supplements, or other forms of treatment reveals that some treatments have a small effect, not significantly larger than that of the placebo. Evaluations of treatment results for tinnitus are hampered by the diversity of the disorder and inability to distinguish between patients with different tinnitus disorders. This means that a cohort of patients with tinnitus may show moderate results to a particular treatment while specific groups of patients within the cohort may show much better results. If, hypothetically, a cohort that is tested comprises three different tinnitus disorders with equal (33.3%) representation and in which the treatment that is tested is only effective in the treatment of one of these disorders, the success will never exceed 33% despite 100% success for one of the tinnitus disorders. If the treatment is only effective in 50% of these participants the total measured success rate will be 16%, still probably acceptable, but the placebo effect could be similar and such a treatment would be regarded as unacceptable.
The results of not being able to test treatments on groups of people with the same form of tinnitus may have excluded treatments that would have been of value if there would have been a possibility to distinguish between different tinnitus disorders.
Another problem in evaluation of treatment results is related to the fact that tinnitus has two different parts, the loudness of the phantom sound and the general effect on a person that is best described as suffering. Treatments may have different effects on these two components; a treatment may significantly lower the suffering component with little effect on the loudness of the sound. Treatments that affect suffering without causing much change in loudness may have been regarded as ineffective as treatment of tinnitus.
The placebo effect is large in tinnitus and that may have caused treatments that have no or little beneficial effect to be chosen.
Subjective tinnitus often has two different kinds of symptoms, one is the commonly recognized phantom sound and the other is what may best be described as suffering. The phantom sound and the suffering from tinnitus may engage different parts of the brain and tinnitus in general may engage different parts of the brain than those activated when physical sounds reach the ears. There is evidence that an interplay between peripheral (ear) pathologies and central auditory mechanisms (auditory nervous systems and other parts of the brain produce the symptoms of many forms of tinnitus). Activation of maladaptive neural plasticity is regarded to play a role in creating the pathologies that are associated with severe tinnitus. The phantom sound of tinnitus, the suffering, and other accompanying symptoms may be caused by the creation of abnormal connections in the brain involving an increased influence of the dorsomedial thalamus, which has direct connections to subcortical structures such as the amygdala, the anterior cingulate, and the insular lobe.
Often the suffering has been associated with the effect of the phantom sound, but there is now evidence that the abnormal neural functions that causes the suffering component of tinnitus is anatomically different from that which causes the phantom sound.
Perhaps the most effective treatments of tinnitus are different forms of behavioral treatments. Treatments using pharmacological agents have had moderate success and there are now efforts to use other methods. Various forms of neural modulation seem to be promising alternatives to pharmacological treatments. Since many forms of tinnitus are assumed to be caused by activation of maladaptive plasticity forms of “unlearning” tinnitus are now being studied in a search for an effective treatment for some forms of tinnitus. More specific forms of “unlearning” tinnitus are now being studied in a search for effective treatments for some forms of tinnitus. In any form of treatment, a person’s reaction to his/her tinnitus is important for the success of treatments. A person with tinnitus may either confront the condition or catastrophize it.
In any form of treatment, a person’s reaction to his/her tinnitus is important for the success of treatments. A person with tinnitus may either confront the condition or catastrophize it.
The poor success of treatment is, to a large extent, a result of not distinguishing between multiple kinds of tinnitus. The state of tinnitus treatment seems be comparable to that of cancer treatment in 1971 when the National Cancer Act launched the “War on Cancer.” The recent increase in success of treatment of cancer is to a large extent a result of realizing that cancer is not a single disease but a group of (very) different diseases. Should tinnitus be regarded in a similar way as a group of diverse diseases, we are likely to see a similar increase in the success of developing powerful and effective treatments for individuals affected by the tinnitus diseases.
The author declares that there is no conflict of interests regarding the publication of this paper.