570931

research-article2015

AORXXX10.1177/0003489415570931Annals of Otology, Rhinology & LaryngologyCianfrone et al

Original Article

Tinnitus Holistic Simplified Classification (THoSC): A New Assessment for Subjective Tinnitus, With Diagnostic and Therapeutic Implications

Annals of Otology, Rhinology & Laryngology 1­–11 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003489415570931 aor.sagepub.com

Giancarlo Cianfrone1, Filippo Mazzei1, Massimo Salviati2, Rosaria Turchetta1, Maria Patrizia Orlando1, Valeria Testugini3, Laura Carchiolo3, Francesca Cianfrone3, and Giancarlo Altissimi1

Abstract Objective: One of the most debated topics in tinnitus is its standard and practical classification. The most popular classification distinguishes subjective from objective tinnitus. Other classifications are based on different features. On the whole, they seem incomplete, and the diagnostic and therapeutic algorithms are often difficult for practical purposes. The aim of this work is to develop a new diagnostic and therapeutic algorithm. Methods: Our model is based on 10 years of experience. In particular, the starting point is the data retrieved from 212 consecutive patients in our Tinnitus Unit between May and December 2013: We found a clear auditory disorder in 74.5% of the population, muscolo-skeletal disorders and/or trigeminal disease in 57.1%, and psychiatric comorbidities in 43.8%. Different features coexisted in 59.9% of the population. Results: Following such data we propose the Tinnitus Holistic Simplified Classification, which takes into account the different tinnitogenic mechanisms and the interactions between them. It differentiates tinnitus that arises from: (1) auditory alterations (Auditory Tinnitus), (2) complex auditory-somatosensory interactions (Somatosensory Tinnitus), (3) psychopathological-auditory interactions (Psychopathology-related Tinnitus), and (4) 2 or all of the previous mechanisms (Combined Tinnitus). Conclusions: In our opinion this classification provides an accurate and easy tailored path to manage tinnitus patients. Keywords tinnitus, hearing loss, somatosensory tinnitus, psychiatric comorbidities, tinnitus classification

Introduction Tinnitus is an acoustic perception not induced by external sources. It is believed that 10% to 25% of the adult population has experienced prolonged tinnitus1-5 and that 4% of adults suffer from chronic tinnitus.6 It is very common in subjects with hearing loss,7 but might be present in individuals with no (apparent) hearing damage (8%-10% of tinnitus sufferers)3,8 and in children.9 One of the most debated topics in tinnitus is its classification, as the need for standards is strongly felt in the scientific community.10 Many different proposals have been suggested. Including: •• Subjective/objective tinnitus: In this popular classification, the distinction is solely based on the presence of tinnitus that can be also perceived by an examiner (objective tinnitus) or tinnitus that can only be perceived by the patient (subjective tinnitus). Objective

tinnitus is mainly caused by vascular (Glomus tumor, angiostenosis, etc) or muscular (myogenic) causes.11,12 Some authors13,14 distinguish somatosounds (sounds induced by mechanical vibrations in the body, eg, muscle contraction and blood flow), that can be either subjective or objective, from tinnitus that is not produced by acoustic mechanical sources and that is always subjective. 1

Department of Otorhinolayngology, Audiology and Ophtalmology, Unit of Audiology, Sapienza University of Rome, Rome, Italy 2 Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy 3 A.I.R.S. Italian Association for the Research on Deafness, Rome, Italy Corresponding Author: Prof Giancarlo Cianfrone, Department of Otorhinolayngology, Audiology and Ophtalmology, Unit of Audiology, Sapienza University of Rome, viale del Policlinico 155, 00186, Rome, Italy. Email: [email protected]

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Annals of Otology, Rhinology & Laryngology  •• Topographic/etio-pathogenetic classification: Several classifications are based on etiologic criteria and are usually constituted by a list of pathologies that can induce tinnitus. Some authors distinguish subjective tinnitus in conductive, sensorineural, and central tinnitus. In particular, sensorineural tinnitus is subclassified in 4 types, depending on the involvement of outer hair cells (OHCs), inner hair cells (IHCs), auditory nerve, and microvascular or osmotic endolymphatic mechanisms.11 In this classification the author gives great importance to OHCs motricity, while other authors report that OHCs might be involved in tinnitus subgroups without any movement.15-17 In addition, this classification includes a further subtyping that is, in our opinion, very complex for a clinical use. •• Tinnitus masking classification: Tinnitus is classified on the basis of tinnitus masking curves in 6 patterns; each pattern is related to different etiologies.18 Another classification is based on residuary inhibition: Masking noise can suppress tinnitus in some subjects, so that tinnitus sufferers can be divided in having a complete, partial, or no inhibition at all.19 •• Tinnitus questionnaires classification: These classifications are based on perceived tinnitus severity that derives from questionnaires such as the Tinnitus Disability Questionnaire,20 the Tinnitus Primary Function Questionnaire21 (that focuses on primary reactions to tinnitus), and the Tinnitus Questionnaire.22 The most commonly used in Italy is the THI (Tinnitus Handicap Inventory) grading: slight, mild, moderate, severe, catastrophic tinnitus.23 This questionnaire might also be considered, in our experience, a good tool to screen for psychiatric comorbidity.24 •• Tinnitus retraining therapy (TRT) categories: This classification,13 mainly used to assess TRT,25,26 distinguishes between patients that are affected by tinnitus only (category 1), tinnitus and hearing loss (category 2), hyperacusis with or without hearing loss (category 3), tinnitus and hyperacusis (category 4), or patients with tinnitus that are not distressed by it (category 0). Other authors27 had already stressed the importance of hyperacusis and the need to distinguish it from the effects of loudness recruitment. •• Tinnitus Research Initiative (TRI) classification: The TRI proposed an algorithm for the diagnosis and treatment of tinnitus in which multidisciplinary management is advised, in particular on the basis of comorbidities that might be found, and a specific treatment is proposed according to the diagnosis.28 Pulsatile and non-pulsatile tinnitus are distinguished, each leading to a different path in the flowchart.

In our opinion, many classifications suffer from a lack of attention to clinical features or a lack of attention to the

underlying neuroplastic mechanisms, as well as to somatosensory and psychological implications; furthermore, the proposed diagnostic and therapeutic algorithms are often difficult to interpret and follow for the clinician. The present work stems from the consideration, that is gaining more and more evidence,1,16,17,29,30 that the many different pathophysiological mechanisms involved in subjective tinnitus fall in 1 or more of the following possibilities: a. auditory alterations, such as a reduction of auditory input or changes in neural transmission and activity, that induce modifications in the neural plasticity network; b. somatic-auditory cross-interactions; c. psychological or psychopathological-auditory interactions. These 3 main mechanisms might lead to tinnitus with specific clinical features and with different diagnostic and therapeutic implications that sometimes may coexist and interact in a single subject.

Rationale of Our Model We agree with those authors31,32 who stress that there are no clearly standardized diagnostic and therapeutic algorithms, hence guidelines should not limit to strong evidence procedures but should extend to procedures that have shown relevant clinical effects in case series of specific groups and subgroups of subjects. The Tinnitus Holistic Simplified Classification, along with its diagnostic and therapeutic algorithms, derives from more than 10 years of experience on over 4300 subjects studied in the Tinnitus Unit of the Sapienza State University Hospital Policlinico Umberto I in Rome. Our model arises from recent observations conducted on 212 tinnitus patients examined between May and December 2013, with a screening stage and a final assessment. Results, not yet published, showed a prevalence of auditory disorders of 74.5% at the screening stage and 76.4% at the final stage, somatosensory features had a prevalence of 62.3% at the screening stage and 57.1% at the final stage, while psychological comorbidities were suspected in 76.4% of the population at the screening stage and confirmed in 43.8% of the total population. In most subjects, 2 or 3 of these features were combined: 86.8% at the screening stage and 59.9% at the final stage. The aim of the present work was to provide an updated interpretative and categorization tool, agile enough to program, for each patient, a path for further diagnosis and treatment. Our holistic approach, that accounts for multi- and interspecialistic features, from the diagnostic and therapeutic point of view, considers tinnitus as part of a complex system with intricate interactions between its constituent features.

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Table 1.  Maneuvers (Modified and Simplified From Woo et al50): The Subject Should Report Any Change in Tinnitus Pitch, Loudness, and/or Lateralization During Performance of the Following Maneuvers. With the head in neutral position resist maximal pressure on:

With the head turned to a side resist torsional force on:

Forehead Occiput Left temple Right temple Ipsilateral temple Contralateral temple

Clenching the teeth Maximal opening of the mouth Protruding the jaw Sliding the jaw to the right and to the left

       

Neck maneuvers

Jaw maneuvers

Our classification refers to subjects suffering from subjective tinnitus. Somatosounds and objective tinnitus are not taken into account in this model because they represent a very special type of perceived sound, easier to detect and interpret, not involving neuroplasticity and with a very low prevalence.

The Classification The Tinnitus Holistic Simplified Classification (THoSC) consists of 3 main classes (when a clearly prevailing pathogenic factor is detectable) and 1 combined class (when any of the 3 different factors interact with each other in a balanced way). These classes are: 1. 2. 3. 4.

Auditory Tinnitus Somatosensory Tinnitus Psychopathology-related Tinnitus Combined Tinnitus.

Auditory Tinnitus. Auditory Tinnitus derives from auditory alterations, that induce hearing loss or changes in auditory qualities leading to modifications in the neural plasticity networks. It has been established that hearing loss or any decrease of peripheral input can trigger a series of ascending neuroplastic reactions up to the auditory cortex, predominantly characterized by hyperactivity1,16,33-35; such reactions, that are partly homeostatic and develop in the short or medium term, but sometimes also in the long run, may ultimately induce the perception of tinnitus. This class should include tinnitus sufferers with a specific pathogenetic event (ie, presbyacusis, noise-induced trauma, sudden sensorineural hearing loss, ototoxic drugs, injuries, Ménière disease, chronic middle ear diseases, otosclerosis, etc) leading to deafferentation processes, increased spontaneous firing rate in the auditory nerve, Inferior Colliculus, Dorsal Cochlear Nucleus, and/or the auditory cortex36,37 or increased synchrony of discharges across the neural population in the auditory nerve, Inferior Colliculus, and/or the Dorsal Cochlear Nucleus.38,39 The presence of very narrow

damages in the cochlea might be responsible for the onset of tinnitus, as normal hearing subjects with tinnitus often have cochlear dead regions40 or outer hair cell damage41 compared to controls. Subjects with retro-cochlear or central lesions (neuronal, nuclear, and/or cortical) are also included in this category. The Auditory Tinnitus is the most common type of tinnitus but requires a correct assessment; it also benefits from the best known and widely shared audiological and tinnitological resources. Somatosensory Tinnitus. Somatosensory Tinnitus derives from complex somatosensory-auditory interactions and cross-modal mechanisms. Tinnitus patients in this class are the ones in which there is a history of cross activity between the somatosensory and auditory systems34,42-46 and the ones in which often some spontaneous movements on somatosensory areas (eg, neck and mandible) clearly modulate tinnitus pitch, loudness, lateralization, and/or onset47-50 (Table 1). Somatosensory-auditory interactions frequently arise from the muscolo-skeletal anatomical district like craniocervical junction, cervical vertebrae, neck and shoulder muscles, and temporo-mandibular junction (TMJ) but can also arise from other districts. Various studies demonstrate auditory connections between the dorsal column and trigeminal systems and the cochlear nucleus via multisensory integrations.44,51-54 Preceding trigeminal stimulation can modulate both the firing rates and temporal response patterns to the acoustic stimulation55,56 in the Inferior Colliculus, which receives inputs from the Dorsal Cochlear Nucleus and the somatosensory nuclei.57 A “somatic tinnitus syndrome”, characterized by unilateral (or 1-side dominant) tinnitus in patients with normal hearing or symmetrical hearing loss and a history of TMJ or head/neck disorders on the tinnitus side, was proposed in 1999 by Levine.46 This class comprises also gaze-evoked tinnitus,58-60 tinnitus that arises from stimulation of the fifth61 and tenth62 cranial nerve, and of the skin.63 This category requires special diagnostic strategies, in order to assess the most effective individual treatment inside a polyhedric panorama of options and needs multidisciplinary specialists in the tinnitus team.

4 Psychopathology-related tinnitus.  Subjects with concomitant and/or related psychopathological disorders are included in this class. Psychiatric disorders are frequent (14%-80% of clinical samples) among patients affected by tinnitus,64 and the relationship between these clinical conditions is complex. Severity of tinnitus, evaluated through Tinnitus Handicap Inventory score, seems to be predictive of associated psychiatric disorders.24 Although the majority of studies on the topic are focused on comorbid depression,65 other psychiatric disorders have also been found to be substantially present in tinnitus patients, such as anxiety, obsessive compulsive, mood, conversion, somatoform,66,67 sleep,68 psychotic,69 cognitive,70 substance use related,71 language,72 sexual,73 personality,74 and eating disorders.75 In addition, some authors reported that the rate of suicide among tinnitus patients is 10 times higher than among the general population.76 The presence of a personological predisposition to neurotic disorders and the lack of coping capabilities could play critical roles in the clinical history of patients affected by severe tinnitus: Positive psychiatric diathesis and history of previous psychiatric disorders are frequent among high distressed tinnitus patients. These data seem to be correlated to genetic and biological reports.77-80 According to recent findings, tinnitus originates at various levels in the acoustic district, while chronification of tinnitus depends on pathological plasticity mechanisms in the tonotopical organization of the cortex.1 Maladaptive neural plasticity might be present in both tinnitus and psychiatric disorders, leading to reorganization of central nervous system (CNS) areas.80 In tinnitus subjects, activity changes can involve both auditory and non-auditory structures81-85; CNS non-auditory areas involved represent nodes of hodological circuits related to psychopathological dimensions; the presence of a psychiatric disorder, on the other hand, represents a facilitating factor to maladaptive neuroplastic arrangements.86 Stress can induce neuroplasticity as well,87 and stressful events are frequent prior to tinnitus onset.24,64 Because of these implications, a screening method to individuate psychiatric comorbidity and an adequate psychiatric evaluation with subsequent treatment is necessary at an early stage.24 Combined Tinnitus.  Combined tinnitus seems to be the most common situation. In many cases it can be extremely difficult to individuate whether specific features are predominant on others at first observation, and we advise to always specify the subclasses (Auditory, Somatosensory, and/or Psychopathology-related Tinnitus). It is also important to notice that tinnitus might have a multifactorial origin and that the factors involved in the generation of tinnitus might differ from those related to its persistence.1 Synergic enhancement of pathological mechanisms has been observed in many cases, for example, an increase

Annals of Otology, Rhinology & Laryngology  in excitatory inputs to the Cochlear Nucleus from the somatosensory system after noise-induced cochlear damage (Auditory + Somatosensory Tinnitus)88; a reactive neck or mandibular muscle tension is often associated to psychopathological conditions (Somatosensory + Psychopathology-related Tinnitus); severe hearing deprivation might induce reactive depression; and stress might facilitate auditory pathways damage via neuroendocrine, immune, and toxic variations linked to stress activation89 (Auditory + Psychopathology-related Tinnitus).

Description of Our Classification and Basic Management Protocol Subject classification is performed through the 2 following stages: (1) screening and preliminary assessment and (2) further investigations and final categorization (Figure 1, Table 2). The second stage leads to the basic therapeutic management of tinnitus, which is not binding but recommended.

First Step: Screening and Preliminary Assessment Anamnestic data collection.  All patients undergo an accurate tinnitus anamnestic interview that also investigates, among others: (1) tinnitus features (eg, pitch and loudness), with particular attention to lateralization (“in the ear” or “in the head”) and temporal characteristics (continuous or discontinuous in the short, medium, or long term); (2) the chronological correlation between hearing loss, psychological stress, somatic conditions, if any, and tinnitus; (3) experience of pitch, loudness, and lateralization changes of tinnitus in relation to spontaneous head, neck, or mandibular movements or the correlation with somatosensory symptoms such as headache and trigeminal pain; (4) possible previous psychiatric disorders or chronological connection between tinnitus onset and psychological or emotional conditions. Clinical data collection. All clinical data that the subject might have already obtained from previous evaluations is collected, both medical and audiological, physiatric, orthopedic, dental, gnathological, neurological, and psychological or psychiatric. Examination.  The examination includes (1) a full ENT examination and (2) audiometric basic tests, such as half-octave pure tone threshold test, immittance tests, Otoacoustic Emissions recording, and measurement of tinnitus parameters (loudness and pitch, masking tests). It should be stressed again that puretone threshold tests might not be sensible enough to highlight very narrow damages.90 The examination also includes (3) somatosensory basic exploration: head and neck and TMJ maneuvers (see Table 1) in order to highlight changes in tinnitus pitch, loudness, or lateralization50; (4) self-assessment

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Figure 1.  Graphic representation of the Tinnitus Holistic Simplified Classification (THoSC) algorithm. See text for details.

questionnaires for tinnitus, hearing loss, and hyperacusis. The questionnaire we use for tinnitus is the Tinnitus Handicap Inventory,23 and in particular the validated Italian version91; for hearing loss the Hearing Handicap Inventory (HHI) is commonly used92; for hyperacusis we chose the Hyperacusis Questionnaire93 and the GUF Questionnaire94. Additional valid questionnaires are available today, especially for tinnitus and tinnitus reactions assessment.21 First categorization.  On the basis of clinical history and clinical data collected during this phase, it is possible to preclassify patients having an Auditory or Somatosensory Tinnitus. Following our experience,24 we preclassify subjects with THI scores ≥38 and/or a history of psychiatric disorders in the Psychopathology-related Tinnitus category. When the identification of 1 factor prevailing on the others is difficult, we inscribe the subject in the Combined Tinni-

tus category. Further diagnostic procedures allow a redefinition of the categorization for a final classification.

Further Diagnostic Investigation and Final Classification In many dubious or borderline cases after the screening stage it is necessary to proceed with further examinations in order to reach a definitive categorization. Auditory Tinnitus.  In these cases, the second level is usually limited to refine audiologic diagnosis and therapeutic procedures, by means of imaging, laboratory tests, and so on. It is possible, though, that a non-Auditory class case in the screening step is later classified as Auditory Tinnitus in the final assessment, in particular if previously classified as Somatosensory Tinnitus but also presenting peculiar

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Table 2.  Summary of Our Classification and Workup (See Text for Details). Tinnitus Category

Main Features and Mechanisms

Auditory Tinnitus

Peripheric or central auditory alterations, with reduction of auditory input or changes in neural transmission and activity; deafferentation mechanisms may be involved (eg, long lasting conductive hearing loss, sensorineural hearing loss, noise and ototoxic injuries, cochlea-labyrinthine disorders, deep and narrow audiometric notches, etc). Cross activity between the somatosensory and auditory systems, frequently arising from the muscolo-skeletal anatomical district (eg, cranio-cervical junction, cervical vertebrae, neck and shoulder muscles, temporo-mandibular junction [TMJ]) and/or other districts (gaze evoked tinnitus, etc). Spontaneous or induced movements on somatosensory areas clearly modulate tinnitus pitch, loudness, lateralization, and/ or onset. Concomitant and/or related psychopathological disorders temporarily linked to tinnitus or influencing tinnitus. Two or more of the above

Somatosensory Tinnitus

Psychopathology-related Tinnitus Combined Tinnitus

“sentinel” symptoms of possible hearing involvement (eg, a strong “in the ear” lateralization, or tinnitus onset shortly after noise exposure, even though there is no clear alteration in pure-tone audiometry). It is to be highlighted that a very narrow frequency damage can generate tinnitus and that a steep audiometric slope is a risk factor for tinnitus.95 Somatosensory Tinnitus. An orthopedic and/or physiatric and/or gnathological examination can highlight 1 of the 2 possible subgroups: (a) with clinically relevant somatosensory features (osteoarthritis, intervertebral disc disorders, pathologic spine curves, myopathies, TMJ disfunction, etc) and (b) with somatosensory dysfunctions that are not clinically relevant. The link to tinnitus is always evident in both subgroups and might be highlighted by specific maneuvers.50 In this class there is hardly any recategorization, but it is to be noted that the cross-modality might not be evident in all cases if we only base our diagnosis on eliciting maneuvers. Indeed, there might be slow and fast responders: In the case of slow responders, an accurate anamnesis might be a better categorization tool. In some cases, as we stated previously, somatosensory involvement can be linked to hearing alterations, in particular in the peripheral auditory pathways. Thus, further audiological tests are needed (high frequency pure-tone-threshold test, Otoacoustic Emissions, Auditory Brainstem Responses, Electrocochleography, etc) if specific features are present, for example, a clear “in the ear” localization of tinnitus, since a cochlear damage might induce hyperactivity in the multisensory neurons of the Dorsal Cochlear Nucleus that are

Main Instrumental Revealing Tests Pure tone audiometry

Maneuvers on somatosensory areas

Tinnitus Handicap Inventory (THI) and psychological questionnaires Two or more of the above

linked to the somatosensory system.96,97 In case of positive outcome of these tests, the patient is recategorized in the Combined tinnitus class (Auditory + Somatosensory Tinnitus). 3. Psychopathology-related Tinnitus.  In this class there is the highest possibility of recategorization. In our protocol, subjects with an initial THI score ≥38 and/or with a history of psychiatric disorders are given further questionnaires: the Symptom Check List (SCL90-R)98 and the Stress-related Vulnerability Scale (VRS).99 The positivity of 2 out of 3 of these tests (THI is included) calls for a pshychiatric evaluation. THI scores ≥38 alone (screening step) have shown an 86.8% sensibility and a 59.1% specificity in detecting psychiatric comorbility in tinnitus; the “full” algorithm (THI + SCL-90R + VRS) yields an even higher sensibility (91.2%) and specificity (79.5%)24; it is to be specified that this class always needs an additional diagnostic stage, including a proper psychiatric examination. This is the least common category by itself but is very common in association to the other classes. Early diagnosis in these subjects is crucial in order to correctly treat them and avoid contraindicated treatments or a negative evolution of tinnitus. 4. Combined Tinnitus.  A further diagnostic level is necessary when the single classes are to be better defined and also in order to determine a proper therapeutic timing that might derive from a clinical predominance of 1 feature over the others. In this class, the most common recategorization is for subjects with a suspect psychiatric factor that further examination might exclude.

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Therapeutic Implications Therapeutic choices may depend on own tinnitus clinic experience, availability of expert professionals in the tinnitus staff, and their capability to interface with one another (Figure 1). In general expert opinion and in our experience, every tinnitus sufferer should be proposed a tailored therapy. Many treatments have been proposed, but none has a high enough level of evidence and no drug has been approved so far for tinnitus by the Food and Drug Administration or the European Medicines Agency.100,101 Many studies investigating different pharmacological and non-pharmacological approaches have been found to be inconclusive,102-104 and we believe that the main reasons for such low evidence is in the fact that such therapies are not tailored to the specific features of each tinnitus sufferer.29,32 This might be particularly true with regards to sound therapies, as some patients report improvement in tinnitus distress while others report worsening of tinnitus in noisy environments.32 It is important to stress out that treatment should not be directed only at tinnitus in itself but also focus on the reactions to tinnitus that a subject might experience, as other authors also noted,32 in order to improve quality of life in these patients. 1. Subjects with Auditory Tinnitus are proposed, given the role of oxidative stress in hearing damage105 and in addition to specific pharmacological and/or surgical therapies for certain condition ethiologically linked to tinnitus (Ménière disease, otosclerosis, sudden sensorineural hearing loss, etc), the use of cytoprotective and antioxidant therapies. Sound habituation therapies such as tinnitus retraining therapy,25,26 especially if associated to an expert counseling, can be considered real rehabilitation treatments since they are aimed at desensitizing and restoring input to acoustic peripheral and central pathways, thus stimulating neuroplastic resetting processes. The choice of devices with which to perform such therapy (hearing aids or sound generators) should be made accordingly to the specific hearing situation of each subject and, in our opinion, should always be accompanied by an expert counseling; this approach, if correctly performed, yields good results.106 2. Subjects with Somatosensory Tinnitus are proposed different options, in a wide somatosensory treatment panorama, according to specific features: For example, TMJ disorders should undergo dental and/or gnathological treatment; physiatric treatments might include Transcutaneous Electrical Nerve Stimulator, Electrical Muscle Stimulation, decontraction and relazation techniques, Arlen’s atlas therapy, and so on. Osteopathic treatment has also proved successful in subjects with dysfunctions or limitations in TMJ and/or spine movements.48 Treatments such as acupuncture have had little success,104 while intravenous lidocaine107 has limited effects, as its injections in jaw or neck

muscles.108 Other specific treatments may be needed according to the specific features of each patient, such as relaxation exercises, biofeedback, and so on. 3. Subjects with Psychopathology-related Tinnitus are proposed an individually tailored therapy on the basis of the specific psychiatric diagnosis, which might comprise pharmacological therapies (selective serotonin reuptake inhibitors,109,110 benzodiazepines,111 mood stabilizers,112,113 psychotherapeutic [cognitive behavioral therapy],114 and neuromodulating treatment (eg, TMS115,116 and tDCS117) aimed at modulating the emotional component of tinnitus to treat tinnitus distress. Rarely these kind of patients will benefit from an early sound therapy, and we advise to implement sound habituation therapies only when psychological improvements are evident. The presence of an expert psychiatrist in the tinnitus staff is critical to obtain the best results. There is no consensus on whether psychiatric treatments in this type of subjects effectively improve reactions to tinnitus or concomitant conditions or tinnitus itself. On the other hand, the improvement of quality of life is generally robust in these cases. Improving the reactions to reduce the perception of tinnitus might be the aim of psychiatric treatments (as well as soundhabituation protocols) in tinnitus sufferers. 4. Subjects with Combined Tinnitus should follow the options for the single classes, trying to harmonize each specific treatment in a protocol that might prove complex. An obvious recommendation is that in subjects with psychiatric disorders, any treatment on Auditory and/or Somatosensory features should be extremely gradual and might even lead to negative reactions in some cases. Sound treatment in subjects with Combined Auditory + Somatosensory tinnitus might begin earlier.118,119 The importance of the decision-making process in all phases of tinnitus assessment and treatment choice should be stressed, as the experience, emotion, and intuition of the examiner may lead to overestimate some features or underestimate others. It is of the highest importance to base decisions on parameters that are as objective as possible in order to minimize the possibility of error. The main difficulty, reducible with a sufficient experience, is in identifying the “ruling” or the “marginality” of different factors.

Conclusions The need for simple algorithms for tinnitus diagnosis and therapeutic management has always been strongly felt among tinnitus health care professionals. Our previous clinical observations strongly support the evidence that almost all of subjective tinnitus fall in 1 or more of 3 main pathogenetic mechanisms: peripheral or central auditory damage

8 or dysfunction, somatosensory-auditory cross-modal interactions, psychological disorders influencing or inducing tinnitus; it is plausible that each mechanism is strictly linked to changes in neuroplasticity. Our aim is to unify all previous experiences11-13,17-20,22-24,28,30,32 and fill in their gaps in order to offer a tool that is both holistic and simple, with a flow chart that guides the clinician from diagnosis to treatment choices. Thus, the Tinnitus Holistic Simplified Classification protocol provides for the identification with relative ease of 3 categories of tinnitus (Auditory, Somatosensory, and Psychopathology-related Tinnitus), and offers a simple path to propose a rational and tailored treatment. We agree with other authors that any treatment on tinnitus sufferers should be based on typization of patients.29,32 Finally, we want to highlight again that our proposed classification refers to subjective tinnitus only, since this is by far the most common. Some forms of tinnitus still evade our classification, for example, tinnitus linked to hypertensive diseases that are not related to cochlear damage, those linked to the tinnitogenic non-ototoxic effect of drugs,120 and those linked to conditions such as epilepsy, endocrine, and immunological disorders without auditory damage.4 Other classifications and algorithms (eg, the one proposed by the TRI28) are very useful tools in these cases and in the case of pulsatile tinnitus. Our model, also, might not be as strictly applicable in other clinics, depending on local health organization and professional staff available. Therapeutic indications might differ in other practices on the basis of different knowhow and experience.16,31,32,102 Of course, research on tinnitus is a constantly evolving field in which new understandings, albeit slow, are continuously growing. Classification and therapeutic options have strongly widened in the past 20 years, but we believe our approach might prove an extremely useful tool in everyday clinical work. We strongly believe that the clinical day-byday observations represent the most appropriate laboratory in tinnitus research, and the best decision-making options derive from the experience, intuition, caring approach to the patient by the clinician and by a multidisciplinary team work. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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