AWMF-Register No. 017/064 Class.: S3€¦ · German S3 guideline Ol 7/064: Chronic tinnitus Current revision: 02/2015 published in: AWMF online The Portal For Scientific Medicine

German S3 guideline Ol 7/064: Chronic tinnitus Current revision: 02/2015

published in:

AWMF online The Portal For Scientific Medicine

AWMF-Register No. 017/064 Class.: S3

Chronic tinnitus 1. Scope and purpose a. Explanation for the choice of the guideline topic Tinnitus is a common complaint of the auditory system that can result in severe disease distress, especially when combined with co-morbidities. However, tinnitus is not a single disease and can take many forms. The principle medical task with tinnitus is to implement diagnostics to identify the individually relevant aetiological factors and accompanying symptoms. Therapy should then be implemented using this differentiated diagnostic assessment as a basis. b. Objective of the guidelines

The presented guidelines are intended to illustrate the current status of diagnostics and therapies available for patients with chronic idiopathic tinnitus. c. Patient target groups

Adolescents and adults with chronic idiopathic tinnitus. d. Facilities and professions addressed Practices of doctors, dentists, and psychological psychotherapists, hospitals, rehabilitation facilities, and spa facilities. e. User target groups / addressees Physicians, particularly those covering the specialties of otolaryngology, phoniatrics and paediatric audiology, psychiatry, psychotherapy, psychosomatic medicine, neurology, and oral and maxillofacial surgery, as well as dentists and psychological psychotherapists. The guidelines also serve to provide information for general practitioners.

2. Members of the guideline group: participation of interested parties a. Representativeness of the guideline group: participating professionals As demanded by the specifications of the AWMF, the guideline group has been assembled in a multidisciplinary manner and representatively for the target audience. The project was publicly announced in 2011 on the AWMF Register on the internet (http://www.awmf-leitlinien.de, AWMF Register number 017/064) to provide all interested parties with the opportunity to participate or comment. The resulting guideline group was convened by the coordinator. During the first consensus conference on 22/11/2011, the representative nature of the group for the further development of the guidelines was assessed by the guideline group. The guideline steering committee was then established. During the course of a secondary nomination procedure, representatives from other interested parties were also found to be necessary. An overview of the final composition of the guideline group is provided below. The tasks of the steering committee included the assurance of implementing the methodological tasks, processing thematic issues, providing support for the substantive work of the participating experts, collating and editing the text drafts prepared by the experts and interested parties, and preparing draft resolutions for the sub-setups involved in approving and adopting the guideline content. b. Members of the consensus conference

1

The following members were nominated by the participating organisations:

1 1

The German Society of General Medicine was invited to participate but did not consider it necessary to involve themselves. The European Tinnitus Association a.s.b.l, 9. Rue des Jardins, L-4591 Differdange, Luxembourg, did not respond.

http://www.awmf-leitlinien.de/


Name Address Professional association / organisation

Prof. Dr. Wolfgang Delb Pfaffplatz 10 67655 Kaiserslautern

German Society of Phoniatrics and Paediatric Audiology (DGPP)

PD Dr. Berthold Langguth University of Regensburg, Clinic for Psychiatry and Psychotherapy, University of Regensburg, Universitaetsstr. 84, 93053 Regensburg

German Society of Psychiatry, Psychosomatics and Neurology (DGPPN)

Prof. Dr. Birgit Kröner-Herwig

University of Goettingen, Georg-Elias-Mueller-Institute for Psychology, Gosslerstr. 14, 37073 Göttingen

German Society of Behavioural Medicine and Behavioural Modification (DGVM) and the German Society for Psychology (DGPs)

PD Dr. Dipl.-Psych. Burkhard Jäger

Hannover Medical School, Centre for Mental Health Clinic for Psychosomatics and Psychotherapy, Carl-Neuberg-Str. 1, 30625 Hannover

German Society of Psychosomatic Medicine (DKPM)

PD Dr. Ingrid Peroz Humboldt University, Charité University Medicine Berlin, Department of Dental Prosthodontics, Geriatrics and Functional Theory, Assmannshauserstr. 4-6, 14197 Berlin

German Society of Dental, Oral and Maxillofacial Surgery (DGZMK) and German Society for Functional Diagnostics and Therapy (DGFDT)

Prof. Dr. Gerhard Hesse Prof. Dr. Birgit Mazurek

Tinnitus Clinic Dr. Hesse at the Bad Arolsen Hospital, Grosse Allee 50, 34454 Bad Arolsen Humboldt University, University ENT Clinic, Charité, Luisenstr. 13, 10117 Berlin

German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHCH)

Prof. Dr. Gerhard Goebel Schoen Clinic Roseneck, Department of Behavioural Medicine, Psychosomatics, Psychiatry and Psychotherapy, Am Roseneck 6, 83209 Prien am Chiemsee

German Physician's Society for Behavioural Therapy (DÄVT)

Prof. Dr. med. Christian Gerloff

University of Hamburg, Department of Neurology University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg

German Neurological Society (DGN)

Prof. Dr. Regina Trollmann

University of Erlangen, University Children's Hospital Erlangen Centre for Social Paediatrics, Paediatric Neurology and Epileptology Loschgestr. 15, 91054 Erlangen

German Society of Paediatrics (DGKJ)

Volker Albert German Tinnitus League, Am Lohsiepen 18, 42369 Wuppertal

German Tinnitus League (DTL)

Dr. Eberhard Biesinger European Federation of Tinnitus Associations (EUTI) Maxplatz. 5 83278 Traunstein

European Federation of Tinnitus Associations (EUTI)

Dr. Harald Seidler German Association for the Hearing Impaired (DSB) Breitestr, 3, 13187 Berlin

German Association for the Hearing Impaired (DSB)

Franz Hermann German Cochlear Implant Society, Rosenstr. 6, 89257 Illertissen

German Cochlear Implant Society

Doris Frensel Tulpe, Karl-Marx-Str. 7, 39240 Calbe Tulpe

Dieter Marten Association for Acoustic Neuroma Leinenweberstr. 13 31655 Stadthagen

Association for Acoustic Neuroma

Prof. Dr. HP Zenner University of Tübingen, University Ear, Department of Otorhinolaryngology, Elfriede-Aulhorn-Str. 5 72076 Tübingen

Coordinator

The following participated as expert appraisers:

Prof. Dr. Annette Limberger

University of Aalen, Optometry and Audiology Anton-Huber-Str. 23 73430 Aalen

German Society of Audiology

Dr. Nicola Strenzke University of Goettingen, Department of Otorhinolaryngology, Robert-Koch-Str. 40 37099 Goettingen

German Society of Audiology

http://www.univis.uni-erlangen.de/form?__s=2&dsc=anew/tel_view&pers=med/KPKJ/pkjnp/trollm&anonymous=1&dir=med/KPKJ/KPKJLA&ref=pande&sem=2011s&__e=131

http://www.univis.uni-erlangen.de/form?__s=2&dsc=anew/tel_view&pers=med/KPKJ/pkjnp/trollm&anonymous=1&dir=med/KPKJ/KPKJLA&ref=pande&sem=2011s&__e=131


PD Dr. rer. pol. Reinhard Vonthein

University of Luebeck; Institute of Medical Biometry and Statistics; Centre for Clinical Studies, University Hospital Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23562 Lübeck

c. Representativeness of the guideline group: participation of patient groups German Tinnitus League, Am Lohsiepen 18, 42369 Wuppertal European Federation of Tinnitus Associations (EUTI), Maxplatz 5, 83278 Traunstein German Association for the Hearing Impaired (DSB), Breitestr. 3, 13187 Berlin German Cochlear Implant Society, Rosenstrasse 6, 89257 Illertissen Tulpe, Karl-Marx-Str. 7, 39240 Calbe Association of Acoustic Neuromas, Leinenweberstr. 13, 31655 Stadthagen d. Advice from the AWMF Professor Dr. med. Ina B. Kopp, Director of the AWMF Institute for Medical Knowledge Management, Philipps University of Marburg, Karl-von-Frisch-Str. 1, 35043 Marburg Dr. Cathleen Muche-Borowski, MPH, Research Associate, Philipps University of Marburg, Karl-von-Frisch-Str. 1, 35043 Marburg e. Organisation of guideline development Coordinator: Prof. HP Zenner Steering committee: Prof. Delb,

PD Dr. Langguth, Prof. Kroener-Herwig, PD Dr. Jaeger, PD Dr. Peroz, Prof. Hesse, Prof. Goebel

f. Guideline secretariat: Professor Dr. HP Zenner Department of Otolaryngology, Head and Neck Surgery The University of Tübingen Elfriede-Aulhorn-Str. 5 72076 Tuebingen, Germany Tel.: 07071-2988001 Fax: 07071-295674 3. Pathophysiological aspects and classification of chronic idiopathic tinnitus Information box 1: Pathophysiological aspects of tinnitus

Tinnitus is a symptom of the auditory system. The current state of knowledge regarding the aetiopathogenesis of tinnitus suggests that its aetiology, whether symptomatic or idiopathic, is often based on a primary pathophysiological process in the ear. With simultaneous hearing loss tinnitus frequency is frequently within the range of the greatest hearing loss (Norena et al. 2002 [161]; Schecklmann et al. 2012 [208]). However, the inner ear damage does not need to be obvious in the pure tone audiogram (Weisz et al. 2006 [242]; Schaette and McAlpine 2011 [207]; Epp et al. 2012 [49]; Tan et al. 2013 [231]). During this pathophysiological process, highly sensitive auditory feedback mechanisms are thought to be amongst the affected processes that may contribute towards the symptoms of tinnitus (summaries in Preyer and Bootz 1995 [190] and Hesse 2008a [81], 2008b [82]).

In individuals seriously affected by tinnitus, central nervous system processing may often result in


pathologically exaggerated stimulus responses, such as exaggerated attention steering towards the tinnitus, induction of anxiety, and insomnia. Currently, central psychophysiological and neurophysiological processing mechanisms, in particular, are thought to be responsible for such pathologically exaggerated stimulus responses.

1) From a psychophysiological perspective, one particular specific learning process has been implicated at the cognitive level (perception level) of the brain, namely cognitive sensitisation (Zenner et al. 2006 [253]). The cognitive sensitisation is thought to be expressed so strongly that it contributes to increased decoupling of the perception of tinnitus from the inner ear. Well-known examples include tinnitus continuing to be perceived despite deafness or after neurectomy of the cochlear nerve. This model is referred to as secondary centralisation of tinnitus (Zenner 1998 [251]). In many cases this leads to a well-characterised increase in attention towards the tinnitus (Roberts et al. 2013 [200]; Zenner et al. 2006 [253]). However, a primarily central cause of the tinnitus is clinically rare. Even psychosocial factors supposedly exert a sensitising effect on tinnitus and, in this way, can increase the perception of a centralised secondary tinnitus (Goebel 1992 [55]; Mazurek et al. 2006 [146, 147]).

2) From a neurophysiological perspective, changes in the neuronal firing rate, neural synchronicity, and

tonotopic organisation occur in the area of the central auditory pathway after cochlear damage (Eggermont 2007 [48]; Roberts et al. 2010 [198]; Tass et al. 2012 [232]). These changes may reflect neuroplastic processes triggered by auditory deprivation. Just as with phantom pain, increased excitation, plasticity, and connectivity along the entire central auditory path can be a compensatory response to the reduced sensory input (De Ridder et al. 2011 [41]; Stein et al. 2013 [224]; Galazyuk et al. 2012 [53]). Amplification of the normal spontaneous neuronal firing rate in the central auditory pathways has been shown and may be dependent, at least initially, on changes in the spontaneous activity in individual auditory nerve fibres (Robertson et al. 2013 [201]; Mulder et al. 2014 [156]). In this way a loss of auditory nerve fibres with a low spontaneous firing rate and high threshold, which are especially vulnerable to noise and ototoxicity, can lead to an increase in spontaneous activity in higher centres and increased perception there (reviewed in Knipper et al. 2013 [119]). Abnormal activity in somatosensory afferents may also lead to increased neuronal activity in the central auditory pathways (Shore 2011 [219]). In addition, patients with chronic tinnitus not only exhibit functional

changes in the auditory structures, but also alterations in the limbic, parietal, and frontal areas (Adjamian et al. 2009 [3]; Lanting et al. 2009 [133]). The functional connectivity between the auditory and non-auditory areas appears to be increased in tinnitus patients (Schlee et al. 2008 [210], 2009 [211]; Burton et al. 2012 [33]; Laureano et al. 2014 [134]; Haller et al. 2013 [67]; Golm et al. 2013 [62]; Pantev et al. 2012 [178]). These tinnitus-associated changes in the neural networks are not static, but change with increasing duration of the tinnitus (Schlee et al. 2008 [210]; Schecklmann et al. 2012 [208], 2013 [209]). The activity in the auditory cortex may correlate with the subjective loudness of the tinnitus (van der Loo et al. 2009 [141]), but it is not sufficient on its own for the tinnitus to be consciously perceived. Only when abnormal activity in the auditory cortex is related to the fronto-parietal attentional network can conscious auditory perception be shown. Tinnitus distress has been associated with co-activation of a non-specific distress network involving the anterior cingulate cortex, anterior insular cortex, and amygdala, among other areas, and plays a role in pain syndromes and somatoform disorders in addition to tinnitus (De Ridder et al. 2011 [41]).

Reviews on the pathophysiological aspects of tinnitus can be found in Tonndorf (1977 [235]), Jastreboff (1990 [102]), Preyer and Bootz (1995 [190]), Zenner (1998 [251]), Moller (2003 [154]), Hallam et al. (2004 [66]), Zenner et al. (2005 [252], 2006 [253]), Mazurek et al. (2006 [147]), Hesse (2008 [81]), and Knipper et al. (2013 [119]).

The following definitions should be used here: a. Objective tinnitus / subjective tinnitus The term "objective tinnitus" is used to describe a situation in which a physical sound source exists in the ear or the vicinity of the ear so that the sound emissions can be heard (e.g., vascular or muscle-related noise). The term "subjective tinnitus" describes a situation in which there is neither an external nor an endogenous sound source. Instead, the tinnitus is caused by abnormal activity in the inner ear and/or the central nervous system (Zenner 1998 [251]). b. Time-course: chronic


In the present guideline, chronic tinnitus is defined as tinnitus lasting at least 3 months. Other time-course definitions for chronic tinnitus are possible. The term sub-acute tinnitus has also been used (Lenarz et al. 1998 [140]; Kempf and Zenner 2008 [108]). For the present definition, the transitions between chronic and subacute

may be fluid rather than static. Furthermore, German guideline 017/064 (2010) only distinguishes between two time courses when considering the choice of therapy according to current knowledge, namely acute and chronic. Thus, the above suggested duration for chronic tinnitus is in accordance with German guideline 017/064 (2010). c. Possible comorbidities Comorbidities (see Table 1) can be pre-existing or tinnitus-induced. Psychiatric and/or psychosomatic comorbidities may occur more often in association with tinnitus (Zirke et al. 2010 [255]; Krog et al. 2010 [124]; Shargorodsky et al. 2010 [217]). Anxiety disorders, depression, and insomnia in particular occur at greater frequency in patients with tinnitus. Depression and other mental disorders represent risk factors for the initiation of tinnitus and can also exacerbate tinnitus (Zenner et al. 2005 [252]; Hebert et al. 2012 [69]). The stronger the tinnitus stress, the more likely the presence of a comorbidity (Goebel and Fichter 2005 [59]; Langguth et al. 2011 [130]). When a psychiatric comorbidity is suspected, further investigation and treatment by appropriate specialists (psychiatrist, neurologist, doctor of psychosomatic medicine) or psychological psychotherapists should follow, and treatment should be provided in accordance with existing guidelines (German S3 guideline for the treatment of unipolar depression; guidelines for the treatment of anxiety disorders). Table 1: Possible comorbidities

1. Mental/psychosomatic/psychiatric comorbidities 1.1 Affective disorders

Dysthymic disorder (ICD-10: F34.1) Major depressive disorder, single (ICD-10: F32.0, F32.1; F32.2; F32.3) Major depressive disorder, recurrent (ICD-10: F33.0, F33.1; F33.2; F33.3)

1.2 Anxiety disorders Phobic anxiety disorders (ICD-10: F40.-) e.g., Specific phobias (ICD-10: F40.2) Other anxiety disorders (ICD-10: 41.-) e.g., Generalised anxiety disorder (ICD-10: F41.1) Mixed anxiety and depressive disorder (ICD-10: F41.2)

1.2 Reactions to severe stress and adjustment disorders

Acute stress reaction (ICD-10: F43.0) Posttraumatic stress disorder (ICD-10: F43.1) Adjustment disorder (ICD-10: F43.2)

1.4. Somatoform disorders

Somatisation disorder (ICD-10: F45.0) Hypochondriacal disorder (ICD-10: F45.2)

1.5. Psychological and behavioural factors associated with disorders or diseases classified elsewhere (ICD-10: F54).

2. Impairment of cognitive-emotional reaction system Concentration disorder Loss of control Catastrophisation Resignation Dysfunctional thoughts Impairment of future life perspective Impaired coping with life Lacking self-esteem Feeling of helplessness 3. Impairment of the behavioural response system Social withdrawal, isolation, avoidance behaviour Relationship disorder


4. Impairment of the physiological response system Sleeping disorders Muscular tension, cervical spine Muscular tension, masticatory apparatus, bruxism Headache Otalgia Light-headedness Vestibular disorder 5. Communication disorders Accompanying hearing loss or deafness Recruitment Disturbance of auditory perception, dysacusis Hyperacusis Social interaction disorders

d. Severity

Measuring the severity of tinnitus can be useful in individual cases when deciding treatment. There are two major methods available, and both provide similar results. Classifying severity according to Biesinger et al. (1998 [23]) is a non-validated but clinically practical, clinical situation orientated, pragmatic approach that takes into

account the effect of ear noise on an individual’s professional and private life: Grade 1: The tinnitus is well compensated, no distress. Grade 2: The tinnitus occurs mainly in silence and has a disruptive effect during distress and other stressful situations. Grade 3: The tinnitus results in permanent impairment of private and professional life, disruptions occur in emotional, cognitive, and physical aspects of life. Grade 4: The tinnitus leads to complete disruption of private life and occupational disability. The 4-stage grading established by Goebel and Hiller is based on a standardised and validated questionnaire: "Tinnitus Questionnaire TQ" (Goebel and Hiller 1998 [56]), short version "mini-TQ12" (Hiller and Goebel 2004 [95]), TBF12 (Greimel et al. 1999 [65]), and the evaluated "Structured Tinnitus Interview (STI)" (Goebel and Hiller 2001 [57]). The questionnaire enables differentiated documentation of the severity of the tinnitus with a stress

score and calculation of quartiles (4-step grading). An additional grade for severity is the degree of compensation (compensation/decompensation). For both of the above grading procedures the following applies: Grades 1 and 2: compensated tinnitus Grades 3 and 4: decompensated tinnitus The following short descriptions apply to the terms compensation and decompensation: Compensated tinnitus: The patient registers the tinnitus but can handle it so that additional symptoms do not occur. There is no or only a slight amount of distress. Quality of life is not significantly impaired. Decompensated tinnitus: The ear noise has an impact on all areas of life and leads to the development or exacerbation of comorbidities (see Table 1 example: anxiety, insomnia, difficulties with concentrating, depression). There is a high level of distress. Quality of life is significantly impaired. 4. Diagnostics Many factors can contribute to the emergence of tinnitus symptoms. Besides otogenic causes, additional triggers and amplifiers from outside the ear must be individually identified or excluded. Diagnosis represents the basis for the consultation and, wherever deemed necessary, the treatment of the patient. Considering what is medically necessary from a cost perspective, one needs to distinguish between diagnostics that may be necessary and those which are only useful on a case by case basis. In this process one should not take action in the form of a rigid protocol that is to be followed for each and every patient; instead, an individual approach needs to be sought


on the basis of the patient’s individual history and underlying diagnostics. In most cases, the diagnosis also serves to clarify whether any co-existing hearing loss is present. 4.1 Case history Case history forms the basis of the diagnosis and can provide the opportunity to initiate diagnostics that may be useful on a case by case basis. It also allows an assessment of severity and any comorbidities that may be present. In this process, both cause-oriented and severity-adapted diagnostics can be performed. The following questions should be asked (consistent with the STI, Goebel and Hiller 2001 [57]):

• In which ear do you hear your tinnitus? (right, left, both sides, is it in the head)? • When did your tinnitus start (right, left)? • Did your tinnitus start suddenly or did it slowly develop (left, right)? • Is your tinnitus pulsating? If so, does it pulsate in time with your heart? • What cause(s) do you suspect for the origin of your tinnitus? • Do you only hear your tinnitus during silence? • Is your tinnitus masked by ordinary ambient noise? • Does your tinnitus drown out all external noise? • Is the volume of your tinnitus always the same during the day or does it change? • Does your tinnitus become louder in normal ambient noise? • Is your tinnitus permanently there during the day? Are there any breaks, and if so, how long do these

breaks last? • Is your tinnitus burdensome? • Does your tinnitus cause you distress? From its onset or only later? • Are you especially sensitive to noise? • Can you influence the tinnitus through self-control, e.g., by diversion of attention, relaxation, or any

other means? • Do other people notice that you hear or understand worse? • Did the tinnitus appear together with hearing loss and/or pressure in the ears? • Do you have problems with balance? • Does the tinnitus occur together with severe vertigo (head-spinning)? • Can the tinnitus be influenced by certain head positions or jaw movements? • Can the tinnitus be influenced by tension in the jaw area? (Vernon et al. 1992 [240]) • Can the tinnitus be influenced by physical exertion? • What medications are you currently taking? • Have you been treated with medication because of severe infection (e.g., tuberculosis, meningitis,

myocarditis, pneumonia, malaria, etc.) or malignant disease, and if so, with what? • Did you have surgery on your ear, or were your ears ever injured? • Have you ever received radiotherapy to the head and neck area because of a malignant disease? • Do you have any cardiovascular or metabolic diseases? • Is there any evidence of other disorders or comorbidities (see Table 1)?

4.2 Possible diagnostics

The following tests should be carried out:

• ENT examination including eardrum microscopy, nasopharyngoscopy, and eustachian tube function • Exploratory neurological examination • Auscultation of the ear and carotid artery, especially with pulse synchronous tinnitus • Audiometry with air and bone conduction • Threshold of discomfort, possibly with categorical loudness scaling (CAVE noise damage) • Determination of tinnitus loudness and frequency characteristics using narrow-band noise and pure

tones • Determination of minimum masking levels using white noise and sine waves; if necessary Feldmann

masking curves and determination of residual inhibition/metachronous tinnitus inhibition • Tympanometry and stapedial reflex, including recording any possible respiration or pulse-

synchronous changes • TEOAE and DPOAE • Exploratory vestibular testing, including caloric reflex testing wherever necessary • Exploratory functional cervical spine diagnostics and examination of the dentition and masticatory

apparatus in a quiet environment for detecting tinnitus modulations • Exploratory functional testing of the facial nerve


For the purposes of recording the subjective severity and any potential distress, a standardised and validated questionnaire inventory is suitable (e.g., the tinnitus questionnaire of Goebel & Hiller, 1998 [56]; Hiller and Goebel 2004 [87]; Greimel et al. 2000 [65]). A quantitative assessment of subjective loudness and the degree of

distress is possible using numeric or visual analogue scales for tinnitus loudness and tinnitus distress, which can then be used to assess the course of the disease and therapy (e.g., Kemp and George 1992 [107]; Wilhelm et al. 1995 [244]; Adam Chic et al. 2012 [1]). In the interests of ensuring international comparability, validated scales are preferred (Lenarz 1998 [140]; Langguth et al. 2007 [128]).

For all methods of investigation involving the application of high sound pressure levels (> 84 dB), a period of at least one week must elapse between the first occurrence or acute exacerbation of tinnitus and investigation due to the risk of additional noise damage occurring in the inner ear. 4.3 Of potential benefit in some cases

Additional diagnostics can be indicated on an individual basis according to a patient’s individual history and their diagnostic assessment. The diagnostics must be medically justified, economically feasible, and contribute significantly towards determining the aetiology of the disease and defining the nature of any counselling and treatment.

1. Extended biographical history or structured tinnitus anamnesis (see 3.1): The physician or psychologist should be aware of the possibility that depressive symptoms may be masked by the symptoms of tinnitus in order to take into account any complication of the habituation to tinnitus due to a patient’s tendency to become depressed. 2. Diagnostics regarding mental impairment, cognitive-emotional processing, and coping with tinnitus (see Table 1.1) should be based on the current patient complaints associated with the tinnitus. The psychosomatic, psychological, or psychiatric diagnostics should be carried out in close cooperation with the ENT specialist by a physician, psychiatrist, psychotherapist, or psychosomatic specialist experienced in the diagnosis and treatment of tinnitus. 3. Brainstem audiometry (BERA) to screen for possible retrocochlear damage, especially with asymmetrical hearing loss of unknown cause, additional restriction of vestibular function, or an unexplained absence of the stapedial reflex. 4. Speech audiometry, possibly with word and sentence testing, if necessary in the presence of external noise in accordance with the current national medical device policies upon suspicion of hearing loss requiring a hearing aid. 5. Dental functional diagnostics and orthopaedic examination upon evidence of defects in the masticatory apparatus or the spine, and functional diagnostic examination for the presence of a temporomandibular dysfunction: If, for example, the question "Do you have pain in the right, left, or both sides of the face?" (Reisman et al. 2009 [195]; Vernon et al. 1992 [240]) is answered with “yes” by the patient, or if there are other reasons to suspect a temporomandibular malfunction (Vernon et al. 1992 [240]), a dental examination should be indicated. 6. Doppler sonography of the arteries supplying the brain (extracranial and transcranial) and sound emissions in the vicinity of the ear when there is evidence of objective ear noises (e.g., pulsatile tinnitus) or a cerebral circulatory disorder, especially when turning the head. 7. Radiographs of the cervical spine and functional imaging when necessary. 8. High-resolution computer tomography of the temporal bones for the detection of osseous destruction, inflammatory processes, and deformities of the temporal bone. 9. Magnetic resonance imaging of the skull with contrast medium and fine layering of the cerebellopontine angle when unclear unilateral deafness is present or with a conspicuous BERA examination to exclude acoustic neuroma, if there is a need to clarify other retrocochlear damage, or for neurological evaluation with suspected central hearing loss. 10. Digital subtraction angiography or angiography/angio-MRT/CT of the cerebrovascular system with pulse synchronous tinnitus. 11. Laboratory diagnostics: a) Infection serology: e.g., Lyme disease, HIV, syphilis b) immunopathology: immunoglobulins, rheumatoid factors, tissue-specific antibodies c) CSF diagnostics: with evidence of an inflammatory process in the CNS


d) metabolism: e.g., blood sugar, blood lipids, liver enzymes, thyroid hormones e) complete blood count 12. Internal examination with abnormalities in laboratory diagnostics or in the case of other suspected cardiovascular, metabolic, or rheumatic disease. 13 When tinnitus is associated with headaches, other differential diagnoses such as trigeminoautonomal headache syndromes (e.g., migraine), proliferative lesions, pseudotumour cerebri, normopressive hydrocephalus, and abnormalities of the cranio-cervical transition are to be considered. For heartbeat synchronous pulsatile tinnitus, differential diagnostics for vascular anomalies (e.g., arteriovenous malformation, aneurysm, carotid stenosis or dissection, sinus vein thrombosis) should also be performed. In such cases, a differentiated neurological diagnosis is necessary.

5. Therapy of chronic tinnitus Defined search strategies and selection criteria were employed to evaluate various therapies for tinnitus, which are described in Annex 2, Chapter 1 and 2.3 - 2.8. For a statistical evaluation of the studies, biometric expert opinions were also consulted

2. Frequently, the analysis revealed that small case numbers and/or small

differences prevented these studies from being evaluated as providing adequate evidence, despite statistical significance (low methodological quality). A difference may have been significant, but it was so small that no clinical benefit was evident (insufficient effect size). Therapy has often been geared to the severity of the tinnitus, as well as the patient’s comorbidities. For decompensated tinnitus, the outcome of an extended biographical, psychosomatic, or psychotherapeutic history also plays another important role. For chronic tinnitus, the determination of tinnitus-sensitising causes, their therapeutic treatment, and the long-term habituation of the patient are key issues. An important aim of treatment is to provide the patient with techniques to achieve as frequent as possible desensitisation, and in some cases even complete habituation, so that the tinnitus can then be dealt with. The basis for each therapy is a diagnostics-oriented consultation combined with patient education (tinnitus counselling). 5.1 Basic therapy a. Tinnitus counselling

The treatment of a chronic tinnitus sufferer should always include a consultation or tinnitus counselling (Kempf and Zenner 2008 [108]; Goebel 2003 [58]; Konzag et al. 2006 [121]; Schmidt et al. 2004 [212]; Hesse and Laubert 2001 [75]) (for details on its implementation see Appendix 1).

Using a comprehensive aetiopathogenic and psychological assessment as a basis, a patient can normally be advised adequately about the future handling of their tinnitus. The commonly espoused statement that there are no treatment options is both inaccurate and unhelpful and may cause the patient to seek alternative, non-recommendable treatment options. Therefore, the key is for the supervising physician to advise the patient regarding his individual aetiopathogenesis, discussing his personal processing of the tinnitus, the prognosis, and tinnitus-reinforcing factors and ear-damaging influences (e.g., avoidance of noise exposure or other tinnitus-aggravating situations). The doctor may also appoint another physician or psychotherapist experienced in treating tinnitus. The original doctor should always, in principle, be available for consultation. This also includes scientifically founded counselling regarding alternative or newer treatments.

2 Anonymised examples of critical study assessments by the guideline group included biometric expert opinions:

• "Whereas in one study a control group may have been missing, in another non-prospective, two-arm patient study the group sizes may have been too small". • "Statistically, a Wilcoxon test was carried out when in fact a chi-square test would have been more appropriate." • "Even with an odds ratio of 6, this test would not report a significant effect due to the low group size, so that the (inappropriate) conclusion of equality from the large p-values would in fact conceal a clinically relevant difference." • "Randomisation by coin toss is no longer the state of the art." • "The evaluation should be carried out using a t-test of individual differences with n-1 = 19 degrees of freedom." • "There are significant inaccuracies in the formulation. As examples, the abstracts have phrases such as ‘proven to be effective’ and ‘proven to be efficient’. These precisely defined types of efficacy can only be demonstrated in the scientific development of a treatment within randomised trials." • "Neither safety has been demonstrated (report on adverse events after the CONSORT extension for Harms, ICH E2, ICH E3) nor has reproducibility been confirmed (according to DIN ISO 5725 by other doctors at other locations and with other patients)." • "The questionnaires and statistical methods used seem reasonable, but they still fail to improve the evidence base." • "The results of the larger study with a longer follow-up are distorted by the high number (40%) of response objectors." • "It is noteworthy that only the available data were considered, but not data from the literature on the effects of other therapies on the answers to these questionnaires."


Counselling the patient is naturally a matter of course, but its effectiveness has only been studied in conjunction with other procedures (Retraining: Jastreboff 1990 [102]; Cognitive BT: Zenner et al. 2013 [254]). Randomised controlled trials (RCTs) on the effectiveness of counselling alone were not found in our search, as the implementation of such studies is problematic for both methodological and ethical reasons. There are no studies in which various forms of counselling have been compared systematically. b. Hearing therapy measures

Regarding cases of frequent simultaneously detectable, and even unilateral, hearing loss and primary central or psychogenic hearing loss, a meta-analysis published in 2010 presented weak evidence that therapeutic measures such as audio therapy may be effective against tinnitus (Hoare et al. 2010 [90]).

Due to the weak evidence, a general recommendation for the implementation of hearing therapeutic measures cannot be made.

Hearing therapies (audio therapy) can be carried out in manualised form (Hesse and Schaaf 2012 [83]). With the help of special exercises, skills for central auditory processing are practised, including directional hearing, focussing, and differentiating the presence of noise with and without hearing aids so that a specific “overhearing of the tinnitus” can be improved (Hesse 2008 [81]). Auditory discrimination training (ADT), in which patients must perform exercises to discriminate frequencies in tinnitus, may also alleviate tinnitus distress (Herraiz et al. 2006 [72], 2007 [73], 2010 [74]). In a meta-analysis, 10 studies on the effectiveness of general auditory perception training were examined, finding a significant improvement in tinnitus distress. However, because of the low methodological quality of all of the studies, only weak evidence exists regarding its efficacy (Hoare et al. 2010 [90]).

Whether audio therapy can be recommended for tinnitus remains uncertain.

There are also reports on the effectiveness of conventional and implantable hearing aids (reviewed in Olze et al. 2010 [169]). Regarding the effectiveness of conventional hearing aids for tinnitus, however, only studies with a

moderate or weak level of evidence exist (Table 2), and the results are contradictory. Some results suggest that the benefits of hearing aids with low and medium frequency tinnitus (up to 6 KHz) are greater than the benefits of high frequency tinnitus (McNeill et al. 2012 [149]), whereas others suggest that, in certain cases with isolated high frequency hearing loss and high frequency tinnitus, a hearing aid may be beneficial for tackling the tinnitus (Trotter and Donaldson 2008 [237]; Searchfield et al. 2010 [214]; Moffat et al. 2009 [153]; Parazzini et al. 2011 [180]). A retrospective survey of 46,843 households whose selection was based on a US census revealed a subpopulation of 3,473 responses from tinnitus sufferers (Kochkin et al. 2011 [120]) who had undergone treatment. Of these respondents, 6.1% (n = 212) used hearing aids to treat their tinnitus. According to a subjective assessment, 52.4% stated that their hearing aids had no effect, whereas 13.7% reported a marked reduction, 14.1% a moderate reduction, and 15.7% a mild reduction in the tinnitus. The subjective effect was more pronounced with greater hearing loss and less tinnitus. In addition, the effect was dependent on the qualifications of the person who carried out the hearing aid fitting. Nevertheless, there is an overall lack of convincing prospective studies that demonstrate any evidence of hearing aids being effective in tinnitus. Evaluable studies on active middle ear implants (implantable hearing aids) with tinnitus are lacking. Accordingly, Hoare et al. (2014 [93]) concluded in their Cochrane analysis

A recommendation for the use of hearing aids cannot be made for the indication of tinnitus.

Hearing aids and middle ear implants can be recommended for the treatment of an appropriate accompanying hearing loss.

Meta-analysis Level of evidence Recommendation Comments

Hoare et al. 2010 Weak Open 10 studies with small sample size investigating the effectiveness of auditory perception training and significant improvement in tinnitus distress, but with low methodological quality

Table 2: Meta-analysis for audio/hearing therapy. PubMed search: "tinnitus AND hearing therapy", "tinnitus AND auditory training". Literature survey: 2014 - 2004; Databases: PubMed, Cochrane. Keywords: hearing aid AND tinnitus, tinnitus AND randomized controlled trial, hearing aid AND tinnitus, tinnitus AND trial, tinnitus AND [hearing therapy, audio therapy, auditory training]. Statistical analysis showed that, for all studies, the sample size and/or small differences despite significance prevented the establishment of a sufficient evidence base (positive distortion, low methodological quality). A difference may be significant but can still be so small that no clinical benefit can be recognised.


In cases of an audiologically proven metachronous tinnitus suppression, a suitable noise CD or noise generator ("Noiser") has been discussed as a possible therapeutic option (Oishi et al. 2013 [167]). A Cochrane meta-analysis evaluated six studies with a total of 553 participants and found that no improvement in tinnitus could be determined after the application of external noise alone or amplified noise (through hearing aids). However, the analysed studies stated that the sound therapy was supportive. A clear assessment of the evidence, however, was not possible due to the multimodal therapeutic approaches that were generally applied (Hobson et al. 2012 [94]).

A recommendation for noise generators/noise CDs cannot be made for the indication of tinnitus.

Studies and meta-analyses Level of evidence

3

Recommendation4 Comments

Trotter and Donaldson 2008 Weak Open 2153 patients, significant improvement in tinnitus perception

Moffat et al. 2009 Weak Open Comparison of tinnitus patients with conventionally fitted hearing aids with high or low tone application, only slight improvement where they were applied more for low-frequency adaptation

Parazzini et al. 2011 Weak Open 91 patients given hearing aids or noise generators on a random basis, both groups improved significantly

Hoare et al. 2014 None None Cochrane meta-analysis

Table 3: Evidence table for hearing aids. PubMed search: "tinnitus AND hearing aids". 2014-2001. Statistical analysis showed that, in all studies, the sample size and/or small differences despite significance prevent the establishment of a sufficient evidence base (positive distortion, low methodological quality). A difference may be significant but can still be so small that no clinical benefit can be recognised (insufficient effect strength).

c. Cervical vertebral spine (CVS) therapy The modulation of tinnitus by manual medical or physiotherapy treatment of the cervical spine has been considered. For muscular tension, osteopathy or muscular feedback have been given (Reishauer et al. 2006 [194]; Biesinger et al. 2008 [24]; Cherian et al. 2013 [36]). However, sufficiently large controlled studies are lacking (Yang et al. 2012 [246]). d. Dental functional therapy/orthodontic therapy

When there are pathological findings at the masticatory apparatus and jaw, especially when they lead to a detectable modulation in tinnitus, corresponding dental functional therapy may be recommended (Bösel et al. 2008 [26]). An analysis of the literature reveals diverse results from certain dental measures in which tinnitus is

associated with temporomandibular dysfunction at an evidence level of Ib. As such, if a temporomandibular dysfunction exists, an attempt can be made to reversibly treat it.

If an impact of the therapy on the tinnitus is confirmed for a period of up to 6 months (i.e., an intra-individual control), definitive dental measures are feasible in individual cases unless a separate dental indication is present (Freesmeyer et al. 2005 [52]).

e. Self-help Self-help organisations assume an additional advisory function. The main purpose of such groups is to facilitate an exchange of information between its members. One meta-analysis suggested an efficacy of self-help interventions on tinnitus distress, but it did not allow any conclusion to be drawn (Nyenhuis et al. 2013 [164]). 5.2 Drug therapy, nutritional supplements, and antioxidants 5.2.1 Medicines

3 Definitions are described in the Appendix.

4 Definitions are described in the Appendix.


A specific drug therapy with proven efficacy for treating chronic tinnitus is not available. In contrast, treatable comorbidities (e.g., depression) can be specifically treated with drugs.

Literature survey: [drug name] AND tinnitus Objective: Evidence regarding pharmacological interventions Search: 18/04/2011-10/03/2014 Search period: 1980 - 10/03/2014 Databases: PubMed, Cochrane Keywords: tinnitus AND randomized controlled trial

tinnitus AND trial tinnitus AND [drug name]

Table 4: Search strategy for the database (see Annex 2, Chap. 2.3 - 2.8)

Many different drugs with different modes of action have been studied for the treatment of tinnitus. Among the publications that could be retrieved were meta-analyses, RCTs with evaluable results, and studies with results that cannot be evaluated. A few randomised clinical trials provided some evidence of some preparations having a possible efficacy, but there is no evidence for a single preparation with positive results replicated with a sufficient level of evidence or in meta-analyses. Accordingly, neither the European Medicines Agency (EMA) nor the Food and Drug Administration (FDA) have approved any preparation for the treatment of chronic tinnitus (Langguth and Elgoyhen 2011 [131]). Based on the above data, no drug can be generally recommended for the treatment of tinnitus. However, psychiatric comorbidities associated with the tinnitus (e.g., anxiety disorders, depression) may need drug treatment. Regarding the type of treatment, please refer to the appropriate guidelines (S3 guideline for the treatment of unipolar depression; German S3 guideline for the treatment of anxiety disorders). Ginkgo biloba. A review from Norway that served as an update of a Cochrane Review evaluated recent randomised and placebo-controlled studies on the efficacy of ginkgo biloba involving a total of 6000 patients found no evidence of efficacy. Instead, the review reported (albeit mild) side effects, such as dizziness, stomach upset, allergic reactions, and sometimes even a tendency to bleed (Roland and Nergard 2012 [202]). As early as 2001 in the British Medical Journal (BMJ), the efficacy of ginkgo extract in tinnitus was assessed in a very large group of patients (1121 participants) in a double-blind, placebo-controlled study. In that study, ginkgo led to the same (low) improvement in tinnitus penetrance and intensity as placebo (Drew and Davies 2001 [47]).

Meta-analyses Level of evidence

Recommendation Comments

Roland and Nergard 2012: Cochrane

None None 6000 patients, no evidence

Hilton and Stuart 2004 None None Cochrane analysis, no evidence

Rejali et al. 2004 None None 6 trials with a total of 1056 patients, no evidence

v. Bötticher 2011 None None Review of 3 trials, 2 gave negative recommendations (Rejali et al. 2004; Drew and Davis 2001) and 1 positive (Holgers et al. 2004), that was taken by the author as the basis for his recommendation

Hilton et al. 2013 None None Cochrane analysis

Table 5: Evidence table for meta-analyses of ginkgo. PubMed search: "tinnitus AND ginkgo", "tinnitus AND ginkgo biloba". Only chronic tinnitus. 2014-1980.

Negative results from RCTs

Level of evidence


Drew and Davies 2001 None None n=1121, double-blind, placebo-controlled, randomised

Han et al. 2012 None None Randomised cross-over study


Rejali et al. 2004 None None Randomised, controlled

Table 6: Evidence table for negative results of RCTs with ginkgo. PubMed search: "tinnitus AND ginkgo", "tinnitus AND ginkgo biloba". Only chronic tinnitus. 2014-1980.

Unusable studies Level of evidence Recommendation Comments

Holgers et al. 1994 none none Insufficient methodology

Reisser and Weidauer 2001 none none Groups too small

Table 7: Evidence table for unusable studies with ginkgo. PubMed search: "tinnitus AND ginkgo", "tinnitus AND ginkgo biloba". Only chronic tinnitus. 2014-1980.

Steroids. Controlled studies for the treatment of chronic tinnitus with systemic steroids were not found in our survey. Our searches revealed only a few studies in which corticosteroids were applied intratympanically, but without any significant effect. One study treated 70 adult tinnitus patients intratympanically with methylprednisolone or saline. The severity of tinnitus distress did not change significantly in either group (Topak et al. 2009 [236]). The other RCT also studied intratympanic application (n = 36) with dexamethasone or saline, revealing no significant differences (Araujo et al. 2005 [9]).

Studies Level of evidence Recommendation Comments

Araujo et al. 2005 None None Intratympanic dexamethasone (n = 36), placebo-controlled

Topak et al. 2009 None None Intratympanic methylprednisolone (n = 59), placebo-controlled

Choi et al. 2013 None None Prospective, placebo-controlled

Table 8: Evidence table of RCTs of intratympanic corticosteroids in chronic tinnitus. PubMed search: "tinnitus AND corticosteroids", "tinnitus AND cortisone". Only "chronic tinnitus". 2005-2014.

Glutamate antagonists. Four glutamate antagonists have been used in clinical studies of tinnitus patients: acamprosite/acamprosate, memantine, neramexane, and caroverine. All antagonists were used as off-label medications or drugs prior to approval.

Studies Level of evidence for effectiveness


Azevedo and Figueiredo 2005; Azevedo et al. 2007

Weak Open n = 50 patients in each case (ITT); randomised, prospective, double-blind placebo-controlled studies

Sharma et al. 2012 Weak Open n = 45 patients (ITT); randomised, prospective, double-blind, placebo-controlled, crossover study; 92.5% improvement

Table 9: Evidence table for tinnitus and acamprosite. PubMed search: "tinnitus AND acamprosite" 2005-2014. Only chronic tinnitus. All studies are too small to provide sufficient evidence of effectiveness. Statistical analysis showed that, in all studies, the sample size and/or small differences prevented adequate evidence from being established despite possible significance. A difference may be significant but still so small that no clinical benefit can be recognised. For example, in Sharma et al. (2012), despite an improvement in the quality of life of 92.5% of patients, statistically there was only weak evidence of effectiveness. ITT: Intention to treat.

Study Evidence level for effectiveness


Figueiredo et al. 2008 None None 60 patients (ITT); randomised, prospective, double-blind, placebo-controlled, crossover study

Table 10: Evidence table for tinnitus and memantine. PubMed search: "tinnitus AND memantine" 1998-2014. Only chronic tinnitus. The study is too small to prove an improvement in the tinnitus inventory (THI). ITT: Intention to treat.


Study Level of evidence for effectiveness


Suckfüll et al. 2011 None None 431 patients (ITT)

Table 11: Evidence table for tinnitus and neramexane. PubMed search: "tinnitus AND neramexane" 2011-2014. Only chronic tinnitus. Neramexane is not an authorised medicinal product. Model study, phase II multicentre study: randomised, placebo-controlled, double-blind, parallel group, four arms, three concentrations. 316 patients completed the study. Due to the high drop-out rate caused by vertigo, the number of cases in the treatment group was so small that no adequate statistical evidence was obtained. ITT: Intention to treat.



Denk et al. 1997 Weak None n = 60 (ITT); single-blind, parallel, placebo-controlled study

Domeisen et al. 1998

None None n = 30 (ITT); single-arm, non-controlled study

Schwab et al. 2004

None None n = 20 (ITT); local application (perfusion) through the round window

Table 12: Evidence table for tinnitus and caroverine. PubMed search: "tinnitus AND caroverine" 1995-2014. Only chronic tinnitus. Inadequately sized studies and no improvements. ITT: Intention to treat.

Other drugs.

Meta-analysis Level of evidence for effectiveness


Baldo et al. 2012 None None Antidepressants, Cochrane analysis, no sufficient evidence for an effect on tinnitus

Table 13: Evidence table for meta-analyses from 1995 to 2014. PubMed Search "tinnitus AND antidepressives AND review". Only chronic tinnitus.



Hurtuk et al. 2011 None None Melatonin, n = 61

Sziklai et al. 2011 None None Pramipexole for tinnitus and presbyacusis (n = 40), decreased "tinnitus annoyance" Jalali et al. 2009 None None Alprazolam 1.5 mg, no effect on THI but an effect on VAS score

López-Gonzáles et al. 2007

None None Sulpiride and melatonin 3 mg (n = 120), tinnitus improvement

Zöger et al. 2006 None None Sertraline 50 mg (n = 76) significantly reduced tinnitus severity questionnaire scores compared to placebo

Stidham et al. 2005 None None Botox A (n = 26) significantly reduced the THI

Sullivan et al. 1993 None None Nortriptyline 50-150 mg (n = 92), significantly reduced "tinnitus-related-disability"

Table 14: Evidence table of positive results in RCTs of drugs from 1993 to 2014. PubMed Search "tinnitus AND therapy OR treatment". Only chronic tinnitus. Statistical analysis showed that, in all studies, the sample size and/or small differences prevented an adequate evidence base from being established despite possible significance. A difference may be significant but still so small that no clinical benefit can be recognised.

Studies and meta-analyses Level of evidence for effectiveness

Recommendation

Comments


Azevedo et al. 2009 None None Piribedil (n = 100)

Mazurek et al. 2009 None None Vardenafil (n = 42)

Dib et al. 2007 None none Trazodone (n = 85)

Olzowy et al. 2007; Liu et al. 2012

None none Atorvastatin (n = 50, 2007), side effects hearing loss (2012)

Piccirillo et al. 2007 None none Gabapentin 900-3600 mg (n = 135)

Witsell et al. 2007 None none Gebapentin 1800 mg (n = 76)

Robinson et al. 2007; Roberts et al. 2011

None none Paroxetine (n = 120, 2006)

Simpson et al. 1999 None none Lamotrigine (n = 31)

Hoekstra et al. 2011 None none Anticonvulsants, Cochrane analysis

Hester et al. 1998 None none Cyclandelate (n = 59)

Rosenberg et al. 1998 None none Melatonin (n = 30)

Westerberg et al. 1996 None none Baclofen (n = 30)

Paaske et al. 1991 None none Zinc (n = 48)

Hulshof and Vermeij 1987 None none Nicotinamide (n = 48)

Hulshof and Vermeij 1985 None none Tocainide (n = 48)

Table 15: Evidence table for negative results in RCTs of medicines 1987-2014. Only chronic tinnitus.





None None Sulpiride and melatonin, not double-blind, inadequate study design

Yilmaz et al. 2004; Akkuzu et al. 2004

None None Misoprostol, insufficient statistics


None None Sulpiride, inadequate study design

Arda et al. 2003 None None Zinc, insufficient statistics

Morgenstern et al. 2002 None None EGb 761, insufficient methodology, high drop-out rate

Bayar et al. 2001 None None Amitriptyline, inadequate study design

Johnson et al. 1993 None None Alprazolam, inadequate study design

Briner et al. 1993 None None Misoprostol, inadequate study design

Hulshof and Vermeij 1985 None None Carbamazepine, inadequate report quality, too little information about study design

Neri et al. 2009

None None Melatonin, n = 170, RCT, inadequate report quality, no figures for drop-outs, means without unity, not meta analysable (no details of SD)

Rosenberg et al. 1998 None None Melatonin, n = 65, RCT, cross-over study5,

insufficient methodology and statistics


None None Sulpride and melatonin, n = 2196, insufficient

methodology and statistics

Paaske et al. 1991 None None Zinc, insufficient methodology and statistics

Sziklai et al. 2011 None None Pramipexole, D2/D3 dopamine agonist, anti-Parkinson drug, inadequate study design, inadequate statistics, observation time only 4 weeks

Yetiser et al. 2002 None None Zinc, insufficient statistics, not controlled, not randomised, no effects

Ochi et al. 1997 None None Zinc, inadequate statistics, cross-sectional comparison with healthy subjects, not randomised

Paaske et al. 1990 None None Zinc, inadequate study design, no distress/annoyance variable, no effect

Table 16: Evidence table for unusable studies from 1990 to 2014. PubMed Search "tinnitus AND therapy OR treatment". Only chronic tinnitus.

5 It remains unclear for the "melatonin group" whether the results only referred to patients who had received melatonin between

T0 and T1, or whether it also referred to those who underwent the second treatment phase. The authors build their conclusions mainly around the secondary result that the patients who stated that they had benefited from the preparation (subjectively, without specifying the criterion!) in the melatonin group had suffered significantly more under tinnitus distress at T0 than those in the placebo group (although no mean difference was apparent). Inadequate report quality with tinnitus, although there was a barely evident but significant improvement in sleep for those receiving melatonin.

6 The origin of the grading remains unclear (general questioning of patients). Effect extents are unclear. The second criterion

(VAS, 0-10) is provided without specifying the names. Inadequate study and report quality.


5.2.2 Nutritional supplements, antioxidants, and drug combinations Our searches revealed no efficacy studies that could be considered.

Studies Evidence level for effectiveness


Cevette et al. 2011 None None Inadequate study design, single-arm, open-label study, not controlled, not randomised

Hesse and Schaaf 2001

None None Inadequate study design, not controlled, not randomised

Joachims et al. 2003 None None Inadequate study design, no tinnitus-related criteria as primary or secondary endpoints

Khan et al. 2007 None None Inadequate study design, not controlled, not randomised, no significant effects

Megwalu et al. 2006 None None Inadequate study design, not controlled, not randomised, "open label" study

Neri et al. 2006 None None Inadequate study design, no intervention

Neri et al. 2009 None None Inadequate study design, inadequate reporting, significance is lacking, no details of SD

Ohsaki et al. 1998 None None Inadequate study design, not controlled, not randomised

Partheniadis et al. 1993


Reiter et al. 2011 None None Inadequate study design, not controlled, not randomised

Savastano and Brescoa 2007


Seidel 1994 None None Inadequate study design

Tan et al. 2007 None None Inadequate study design, no tinnitus distress endpoint

Table 17: Evidence table for antioxidants and dietary supplements. 1998-2014. PubMed search "tinnitus AND nutritives", "tinnitus AND dietary supplements", "tinnitus AND therapy OR treatment". Only chronic tinnitus.

5.3 Cognitive behavioural therapy (CBT)

For structured tinnitus-specific variants of cognitive behavioural therapy, medicinal efficacy for tinnitus distress and quality of life has been demonstrated in a number of controlled studies (Henry 1996 [71]; Kröner-Herwig 2003 [126]; Zachriat and Kröner-Herwig 2004 [249]; Andersson et al. 2005 [8]; Kaldo 2007 [106]; Weise 2008 [241]; Zenner et al. 2013 [254]; Cima et al. 2014 [39]). Such intervention is aimed at reducing attention focussing towards the ear noise, bringing about a re-evaluation of the tinnitus and its consequences ("decatastrophisation", reduction of anxieties) and improving coping (e.g., confidence in one’s own ability to influence the condition, task-avoiding behaviour). Typically, the therapeutic procedure is laid out in published manuals, is structured and manualised, and describes a limited therapeutic context. The manuals are often designed for group therapies (for the German language version see Kröner-Herwig 1997 [125]; Delb et al. 2002b [43])

8 7, but even individualised

therapies are based on such manuals (Zenner et al. 2013 [254]). According to evidence levels stipulated by the Centre for Evidence-Based Medicine (Oxford, UK), this form of CBT meets an evidence level of la (i.e., systematic reviews based on RCTs assessing tinnitus distress and quality of life). A typical RCT [7] revealed a mean effect size of 0.86, indicating high effectiveness. The aforementioned Cochrane meta-analysis (Martinez-Devesa 2010 [145]) of five RCTs revealed a significant difference from controls (SMD 0.64, 95% CI 0.29 to 1.00, I2

= 0%). Significant reductions in depression scores were also observed in individual RCTs (effect sizes from 29 to 0.37, SMD 0.37, 95% CI 0.15 to 0.59, I

2 = 0%) (Martinez-Devesa 2010 [145]). However, the actual perception

of the loudness of the tinnitus does not change with CBT.

7 A recent Cochrane analysis based on clinical RCTs characterised the evidence-based CBT with tinnitus as follows: "Cognitive behavioural

therapy (CBT) is a structured, time restricted therapy ...." [158], i.e., each session is structured using a manual. In addition, the number of sessions is restricted as a matter of principle. If the goal of therapy is achieved ahead of time, the treatment can be stopped before reaching the maximum number of sessions (Zenner et al. 2013 [271]). Otherwise, the therapy is finished when the maximum number of sessions prescribed in the published manual is reached (Kröner-Herwig 1997 [134]). As a result, the therapist follows an evidence-based treatment plan in either group or individual therapy (for the German language version see Kröner-Herwig 1997 [134] and Zenner et al. 2013 [271]).


Accordingly, it is recommended here that tinnitus-specific CBT (tCBT) be carried out using an evidence-supported and structured therapeutic manual.

Whether CBT-based self-management training based on written or internet-derived learning materials (no direct or reduced personal contact with the therapist; contact via telephone or email) can be qualified as effective has not yet been confirmed (Nyenhuis et al. 2013 [162]). However, the meta-analysis did show that the self-implementation of coping strategies compared to passive control groups is able to provide significant advantages in terms of tinnitus distress and that are not significantly different from face-to-face therapy. However, the differences from the control groups were only of a moderate magnitude (effect sizes of 0.33 to 0.48). Also, there is evidence of some positive distortion (e.g., publication bias). However, the acceptance of such therapies is already well established among patients (Andersson et al. 2004 [7]; Hesser et al. 2012 [84]; Kaldo et al. 2007 [106]; Nyenhuis et al. 2013 [163]).

Meta-analyses Level of evidence


Andersson and Lyttkens 1999 High Strong recommendation CBT, evidence level Ia, effect size 0.86

Martinez-Devesa et al. 2010 High Strong recommendation CBT, evidence level Ia, Cochrane analysis

Nyenhuis et al. 2013 Weak Open Management therapy

Cima et al. 2014 High Strong recommendation CBT, evidence level Ia

Studies with German language CBT

Kröner-Herwig et al. 1995; Kröner-Herwig et al. 2003; Zachriat and Kröner-Herwig 2004

High Strong recommendation Group therapy, CBT, evidence level Ib

Zenner et al. 2013 High Strong recommendation Individual therapy, CBT, evidence level Ib

Table 18: Evidence table for tinnitus-specific CBT. PubMed search "tinnitus AND cognitive behavioral therapy, tinnitus AND psychological therapy ". 1999-2014. Only chronic tinnitus. The presentation of the individual studies was restricted to CBTs carried out in the German language.

5.4 Other forms of therapy 5.4.1 Electrical and electromagnetic methods a. Cochlear implants

In patients with profound hearing loss or deafness, a cochlear implant may be indicated to improve hearing. If such patients also have tinnitus, improvement of the tinnitus is often observed retrospectively and deemed significant (Kim et al. 2013 [113]; Olze et al. 2010 [169], 2011 [170]; Sampaio et al. 2011 [205]; Stark and Helbig 2011 [223]; Bovo et al. 2011 [28]; Amoodi et al. 2011 [4]). This is true not only for unilateral cochlear implant implantation with homolateral tinnitus (Punte et al. 2011 [191]), but also for contralateral (Punte et al. 2011 [191]) and bilateral (Pan et al. 2009 [177]; Zeng et al. 2011 [250]; Olze et al. 2012a [171], 2012b [172]) tinnitus. With a second implant, quality of life can be improved further and in relation to the tinnitus (Olze et al. 2012 [173]).

Comparable results have been observed retrospectively with unilaterally deaf patients who suffered with very distressing tinnitus and were provided a cochlear implant, (Vermeire and Van de Heyning 2009 [239]; Buchner et al. 2010 [30]; Arndt et al. 2011a [17], 2011b [18]; Blasco and Redleaf 2014 [25]). The effect on tinnitus was also independent of the quality of the tinnitus. Narrowband noise, tonal tinnitus, and even polyphonic tinnitus responded equally (Punte et al. 2011 [191]).

Prospective observations of the course of tinnitus with hearing loss leading to cochlear implant implantation came to the same conclusion, although the number of study participants overall was very low (Bovo et al. 2011 [28]; Pan et al. 2009 [177]; Kompis et al. 2012 [121]). In a prospective study of 174 cochlear implant users, 71.8% had

tinnitus before implantation, but in 20% the tinnitus was gone within 6 months of surgery, and in 51.2% there was at least an improvement (Kompis et al. 2012 [121]). Improvement was also apparent when stress-processing and coping strategies were queried (Olze et al. 2012b [172]). Exacerbations of tinnitus are possible but remain the exception. Also, in one non-controlled pilot study (Heyning et al. 2008 [86]) involving 21 cochlear implant

implantations for the indication of unilateral tinnitus, the authors reported that the patients significantly benefited.


In some cases with chronic tinnitus in which the cochlear implant had only occasionally if at all affected the tinnitus, specific electrical stimuli were applied (biphasic, at a fixed stimulation rate of 100-200 or 5000 stimuli/sec at a pleasant volume). Some of the patients reacted positively to at least one of the tested stimulation modes, i.e., the tinnitus was partially suppressed (Chang and Zeng 2012 [35]). An electrode that was completely ("full length”) inserted was superior to a partially inserted electrode (Punte et al. 2013 [192]). Systematic studies are lacking. This procedure is still to be considered experimental at this time. Studies of cochlear implant implantation for the indication of tinnitus alone without hearing loss do not exist.

Tinnitus with simultaneous cochlear implant-relevant hearing loss (also unilateral) may reinforce the indication for a cochlear implant but may not represent an indication on its own without such hearing loss (Kompis et al. 2012 [121]; Pan et al. 2009 [177]; Sampaio et al. 2011 [205]; Stark and Helbig 2011 [223]; Olze et al. 2010 [169]). Therefore, a recommendation cannot be made for cochlear implant implantation solely because of tinnitus. Instead, a primary indication of deafness or hearing loss bordering on deafness must be present.

Meta-analyses Recommendation with simultaneous chance of improving hearing

Comments

Olze et al. 2010 Recommendation Review of device-based procedures including CI

Stark et al. 2011 Recommendation Review

Sampaio et al. 2011 Recommendation Review

Blasco and Redleaf 2014

Recommendation Review

Prospective studies Recommendation Comments

Kompis et al. 2012 Recommendation 174 CI patients, 51% improvement in tinnitus, in 20% tinnitus was completely suppressed

Bovo et al. 2011 Recommendation 51 CI patients, 36 with tinnitus, in 75% tinnitus distress was significantly reduced, complete suppression in 36%

Amoodi et al. 2011 Recommendation 142 CI patients, complete tinnitus suppression in 37%

Punte et al. 2011 Recommendation 26 unilaterally deaf patients with tinnitus, CI brought about improvement in all 26 patients

Vermeire and v.d. Heyning 2009

Recommendation 20 unilaterally deaf patients with tinnitus, CI brought about improvement in all 20 patients

Arndt et al. 2010 and 2011

Recommendation 11 unilaterally deaf patients with tinnitus, CI caused complete suppression in 5 and improvement in 3 patients

Büchner et al. 2011 Recommendation 5 unilaterally deaf patients with tinnitus, CI caused improvement in 3 patients

Chang and Zeng 2012 Recommendation 13 CI patients whose tinnitus remained unaffected, special electrical stimulation was effective in 69%

Retrospective studies Recommendation with simultaneous chance of improving hearing

Comments

Kim et al. 2013 Recommendation 35 CI patients, tinnitus improved in all patients

Vallés-Varela 2013 Recommendation 20 patients, including 13 patients with tinnitus improvement

Olze et al. 2011 Recommendation 39 tinnitus patients, improved quality of life and tinnitus distress

Olze et al. 2012 Recommendation Improved tinnitus distress, stress coping, and quality of life with 2 implants

Prospective studies Recommendation for the indication of unilateral tinnitus

Comments

Heyning et al. 2008 Open 21 patients with unilateral tinnitus, pilot study

Table 19: Evidence table for cochlear implant (CI) and tinnitus 2010-2014. PubMed Search "tinnitus AND cochlear implant". Only chronic tinnitus. The studies are small, with one exception. Statistical evidence for the sole indication of tinnitus is lacking.


Nevertheless, the studies are listed here because, unlike drug trials, a statistically desirable group size cannot be justified for ethical reasons when a CI has to be surgically implanted. Therefore, the recommendation is not based on the indication of CI implantation solely for tinnitus. Instead, a primary indication of deafness or hearing loss bordering on deafness must be present.

b. Electromagnetic procedures Various electromagnetic stimulation methods have been studied for the treatment of tinnitus. Repetitive transcranial magnetic stimulation over the temporal or temporoparietal brain regions has been studied in 15 randomised placebo-controlled trials (Klein Jung et al. 2005 [114]; Plewnia et al. 2007 [185]; Rossi et al. 2007 [204]; Smith et al. 2007 [221]; Khedret al. 2008 [110], 2009 [111]; Marcondes et al. 2010 [144]; Anders et al. 2010 [5]; Mennemeier et al. 2011 [152]; Piccirillo et al. 2011 [188]; Chung et al. 2012 [38]; Plewnia et al. 2012 [186]; Langguth et al. 2014 [132]; Piccirillo et al. 2013 [189]; Lee et al. 2013 [136]; Hoekstra et al. 2013 [96]). The majority of studies (n = 10) showed a significant efficacy of rTMS. Systemic reviews, including a Cochrane analysis, concluded that short-term treatment effects are detectable, but more studies are needed to determine longer lasting effects (Peng et al. 2012 [183]; Meng et al. 2011 [151]). The body of data on this is restricted, and long-term effects (and side effects) have not been adequately studied. Cohort studies or randomised trials without placebo controls involving a total of 1140 patients (Tables 19 and 20) have shown an effect of transcranial magnetic stimulation and revealed that the treatment effects in some cases are detectable 4 years after treatment (Burger et al. 2011 [32]). However, at least one large-scale, prospective, controlled study would be preferred. Whether a recommendation can be made remains uncertain. For transcranial direct current stimulation, a meta-analysis is available that suggests a significant reduction in the intensity of tinnitus after direct current stimulation, although the power of this analysis is restricted by the overall small number of studies (Song et al. 2012 [222]). The evidence base is only moderate.

Any recommendation for electromagnetic procedures remains uncertain.

Other electrical stimulation methods (e.g., transcutaneous electrical stimulation in the area of the ear and in the area of the cervical spine; vagus nerve stimulation; transcutaneous vagus nerve stimulation) have been examined in isolated pilot studies, which allows no definitive assessment to be made (Teismann et al. 2014 [234]). Therefore, these methods are classified as experimental. The evidence base is weak.

No recommendation can be made.

Studies Number of patients

Design Assessment by the authors of each study

Results

Kleinjung et al. 2005

14 Randomised, controlled, cross-over

Positive Significant difference in the reduction of TQ

Plewnia et al. 2007


Positive Significant difference in the reduction of TQ

Rossi et al. 2007


Positive Significant reduction of tinnitus severity after active stimulation compared to sham stimulation, no prolonged effect

Smith et al. 2007


Positive Effect detectable in 3 of 4 patients

Khedr et al. 2008, 2009

66 Randomised, controlled, parallel design

Positive Significant reduction in all three active conditions compared to the control group, effects still significant one year after treatment

Marcondes et al. 2010


Positive Significant reduction of tinnitus severity by active stimulation compared to sham stimulation, detectable 6 months after treatment

Anders et al. 2010


Positive Significant reduction of TQ and THI scores for active stimulation compared to sham stimulation, effects still detectable 6 months after the end of the stimulation treatment


Mennemeier et al. 2011


Positive Reduction in tinnitus loudness after active TMS compared to control

Piccirillo et al. 2011

14 Randomised controlled, cross-over

Negative No significant difference between the active treatment and control groups

Chung et al. 2011


Positive Significant reduction in the TF and THI after active compared to sham stimulation

Plewnia et al. 2012


Negative Bilateral theta burst without significant effect on tinnitus compared to sham

Langguth et al. 2012


Negative Significant reduction after active TMS, no change after sham TMS, no significant difference between groups

Piccirillo et al. 2013


Negative No significant difference between active and sham temporoparietal rTMS

Lee et al. 2013 15 Controlled, cross-over

Positive Significant tinnitus reduction after 1 Hz rTMS but not after sham

Hoekstra et al. 2013


Negative Bilateral 1 Hz TMS for 5 days was not superior to placebo treatment

Total 553 Mostly positive

Table 20: Evidence table for randomised sham-controlled studies on transcranial magnetic stimulation (TMS). 2005-2014. PubMed Search "tinnitus AND tmr", “tinnitus AND magnetic", "tinnitus AND transcranial". Only chronic tinnitus.

Studies Number of patients

Design Assessment by the authors of each study

Results


28 Cohort study Positive Significant reduction of TQ


45 Cohort study Positive Significant reduction of TQ


32 Two active conditions; randomised, controlled, parallel design

Positive Significant improvement for both stimulation conditions

Lee et al. 2008

8 Cohort study Negative No significant reduction in tinnitus



Positive Significant improvement for both stimulation conditions, 3 months post-therapy significant superiority of combined stimulation



Positive Significant improvement for both stimulation conditions

Burger et al. 2011

235 Cohort study Positive 21.3% of those treated had a significant improvement (reduction of TQ by an average of 18.3 points), 4 years after treatment the average reduction was sustained and by over 14 points


18 Cohort study, comparison with historical control group

Positive TQ reduction for the whole group, no additional effect through the administration of bupropion


Kreuzer et al. 2011


Positive Reduction of tinnitus severity in both groups, more pronounced with combined frontal and temporal stimulation

Lefaucheur et al. 2012

6 Cohort study Positive Clinical improvement in 5 of 6 patients

Lehner et al. 2012

538 Cohort study Positive Significant reduction of tinnitus severity after temporal and combined frontal and temporal stimulation

Lehner et al. 2013

45 Cohort study, comparison with historical control group

Positive Bilateral frontal and temporoparietal rTMS was significantly superior to left temporal stimulation in the follow-up 3 months after treatment

Park et al. 2013

11 Cross-over Positive Combined frontal and temporal rTMS resulted in a significant reduction in THI, whereas temporal rTMS alone did not

Kim et al. 2013


Positive Reduction of THI score after ipsilateral and contralateral 1 Hz rTMS treatment

Forogh et al. 2014


Positive 4 sessions of continuous theta burst stimulation (cTBS) and 4 sessions of 10 Hz rTMS both reduced tinnitus with cTBS being significantly more effective

Total 1140 Overwhelmingly positive

Table 21: Evidence table for studies without sham controls on transcranial magnetic stimulation (TMS). Literature survey: Transcranial magnetic stimulation for the treatment of tinnitus, search period: 1980-2014, PubMed Search "tinnitus AND tmr", “tinnitus AND magnetic", "tinnitus AND transcranial". Only chronic tinnitus. Databases: PubMed, Cochrane.

5.4.2 Acoustic procedures

The sole use of noise with an unmodulated frequency (using a noiser/masker or CD) was presented in Chapter 5.1b. a. Retraining therapy (TRT) The essence of retraining therapy (TRT) is a combination therapy consisting of counselling and noise with an unmodulated frequency developed in the English-speaking world, where it was introduced mostly by non-medical professionals (Jastreboff 1999 [103]; Henry et al. 2006 [70]). The importance of counselling has already been dealt with in Chapter 5.1a. The non-evident therapeutic benefit of noise generators was discussed in Chapter 5.1b. Regarding the effectiveness of the combination in classical TRT, one Cochrane meta-analysis produced no persuasive evidence (Phillips et al. 2010). In contrast, a working group set up in 1996 by the ADANO, the DGHNO-KHC took on the task of adapting TRT to the German-speaking world and defining quality requirements. In a publication appearing in 1998 (ADANO 1998 [2]) a combination of CBT interventions and sound therapy ("TRT according to ADANO") was proposed, and in a team of otorhinolaryngologists, qualified psychotherapists (doctors or psychologists), and hearing aid acousticians (Kröner-Herwig 1997 [125]; Biesinger et al. 1998 [23]; Svitak et al. 2001 [228]; Delb et al. 2002a [42], 2002b [43]; Hesse 2002 [78]; Goebel 2003 [58]; Seydel et al. 2008 [216]). There are no studies showing any additional benefits of sound therapy within the context of TRT according to ADANO beyond CBT for the patient. The therapeutic benefits seem to lie within those afforded by evidence-based CBT, to which therapy can be restricted.

In the newer version of the AWMF guidelines (017/064 from 2010), as well as in these guidelines, TRT was and is not recommended.

Studies and reviews Evidence level for the sound therapy


ADANO 1998 None None, instead perform CBT

In addition, especially cognitive therapy


Biesinger et al. 1998

None None, instead perform CBT

In addition, especially group behavioural therapy

Svitak et al. 2001


Additionally cognitive therapy

Delb et al. 2002a


Additionally group behavioural therapy

Delb et al. 2002b



Hesse 2002



Goebel 2003

None None, instead perform psychotherapy

Especially patients with grade IV

Seydel et al. 2008


In addition, especially group therapeutic approaches

Oishi et al. 2012

None

None 95 TRT patients with noise generators, retrospective, 2 years follow-up, significant improvement, no control

Newman and Sandridge 2012

Weak Open

Too small a group, 56 patients, comparison of noise generators with a music training device (Neuromonics), both groups improved significantly

Phillips and Ferran 2010

Hoare et al. 2011 None None Meta-analysis

Table 22: Evidence table for tinnitus and sound generators. PubMed search: "tinnitus AND sound generators OR sound therapy", "tinnitus AND noise generators OR noise therapy "tinnitus AND noiser", "tinnitus AND masking" tinnitus AND masker”. 1996-2014. Only chronic tinnitus.

b. Music therapy Passive music therapy. Tinnitus-centred music therapy is a treatment in which music that has been modified according to the frequency of the tinnitus is applied. An observational study of 158 patients with acute and 18 patients with chronic tinnitus examined this form of therapy (Cramer 2002 [40]). Another working group reported on the first patient-specific filtered applications of music, also referred to as "notched music", to 39 and 24 patients, whereby one study contained a control population and was conducted in a pseudo-randomised and double-blinded manner (Okamoto et al. 2010 [168]; Teismann et al. 2011 [233]). Because of the results of this study, a large-scale Phase III study was initiated (Pantev et al. 2014 [179]).

The results available until now do not suffice to allow any evidence-based recommendation.

Active music therapy. Active music therapy is conducted under the guidance of a music therapist. Argstatter et al. (2007 [11], 2008 [12], 2010 [13], 2012a [14], 2012b [15]) and Grapp et al. (2013 [63]) published a number of studies on active music therapy. This is a manual-based and standardised music therapy of nine 50-minute sessions held on 5 consecutive days. A recently published controlled and pseudo-randomised study produced the first evidence (Argstatter et al. 2014 [16]). Compared to controls (counselling), which had a 33% improvement in scores on a tinnitus questionnaire inventory according to Göbel-Hiller, the music therapy achieved an improvement of 66% (odds ratio 4.34 with a confidence interval of 2.33-8.09). Methodologically, this can be referred to as a moderately validated therapy programme and the effectiveness should at least be reproduced in another study at another centre or in a multi-centre study.

The results available until now do not suffice to allow an evidence-based recommendation.


Unfiltered music Evidence level Recommendation Comments

Argstatter et al. 2010 None None No control

Hesse and Schaaf 2007

None None Inadequately sized groups

Argstatter et al. 2007, 2008, 2012a, 2012b; Grapp et al. 2013

None None Depending on the publication, for example, effect size d = 1.73 (Cohen's); controlled, but inadequately sized groups, statistically inadequate, control groups too small

Argstatter et al. 2014 Weak Open n = 290, pseudo-randomised, controlled (OR 4.34, CI 2.33-8.09), confirmatory study is still pending

Filtered music Evidence level Recommendation Comments

Cramer 2002 None None Nickel et al. 2005 Weak Open Small groups, controlled

Okamoto et al. 2010 Weak Open Small study, pseudo-randomised, double-blind

Teismann et al. 2011 None None No control

Table 23: Evidence table for music therapy. 2002-2014. PubMed Search "tinnitus AND music". Only chronic tinnitus.

c. Acoustic neuromodulation Acoustic "coordinated reset" neuromodulation is designed to eliminate central excitation circuits that are presumed to be pathologically synchronised in tinnitus. This is a procedure for which no experience has been gained with sufficiently large groups. An initial clinical dose-finding study with 63 patients (single-blinded, randomised, placebo-controlled) yielded significant improvements when using Goebel-Hiller’s tinnitus questionnaire as the test instrument (Tass et al. 2012 [232]). However, the results of large Phase III studies are not yet available (Hoare et al. 2013 [92]).

No recommendation can be made for this therapy.

Coordinated reset neuromodulation Evidence level Recommendation Comments

Tass et al. 2012 None None Randomised, controlled dose-finding study, inadequately sized

Table 24: Evidence table for acoustic neuromodulation. Study period 2012-2014. PubMed Search "tinnitus AND reset". Only chronic tinnitus.

5.4.3 Hyperbaric oxygen

A benefit from hyperbaric oxygen for the treatment of chronic tinnitus has not been proven.

(Bennett et al. 2012 [22]).

Meta-analysis Level of evidence Recommendation Comments

Bennett et al. 2012 None None Cochrane analysis

Table 25: Evidence table for meta-analyses regarding hyperbaric oxygen treatment. PubMed Search "Tinnitus AND oxygen AND review". Study period 2000-2014. Only chronic tinnitus.

5.4.4 Acupuncture

Studies showing an effectiveness of acupuncture do not exist.

(Kim et al. 2012 [121]).

Meta-analysis Evidence level Recommendation Comments

Kim et al. 2012 None None Meta-analysis, insufficient body of data

Table 26: Evidence table for meta-analyses regarding acupuncture. PubMed Search "tinnitus AND acupuncture", tinnitus AND chinese therapy". Study period 2000-2014. Only chronic tinnitus.


5.5 Therapeutic setting

CBT can be applied as group (Kröner-Herwig 1997 [125]) or individual (Zenner et al. 2013 [254]) therapy in appropriately qualified facilities, such as practices, clinics, or spa and rehabilitation centres.

If a patient with severe decompensation due to tinnitus-induced helplessness cannot be treated on an outpatient basis, and if there is significant psychiatric or psychosomatic comorbidity, primary inpatient treatment should be indicated (Goebel 1992a [54], 1992b [55], 2005 [60]; Graul et al. 2008 [64]). If all outpatient treatment options are exhausted, inpatient treatment may then follow.

The recommendation for inpatient treatment applies only when the therapy includes the above-mentioned evidence-based treatment methods (Hesse 2008a [80], 2008b [81]; Hesse et al. 2001 [77]; Goebel et al. 2006 [61]), and treatment can only be performed with additional measures employed in a hospital. The therapeutic efficacy of an inpatient stay regarding psychological suffering has only been substantiated insufficiently by randomised trials, with the effect being only weak to moderate. Nevertheless, the typical measures employed in a hospital may be necessary wherever compensation for patient helplessness is required.

Studies Evidence level Recommendation Comments

Graul et al. 2008

Only with regard to distress, moderate

Recommendation for the treatment of distress, if successful followed by CBT

n = 179, prospective, 67% improvement in distress

Hesse et al. 2001

Only with regard to distress, weak

Open n = 1841, retrospective evaluation with waiting list as a control, 90% improvement in distress

Goebel et al. 2006

Only with regard to distress, weak

Open n = 434, 15-year catamnesis, waiting list as a control group

Table 27: Inpatient treatment for decompensated chronic tinnitus. PubMed search: "Tinnitus AND inpatient therapy", only decompensated tinnitus. 1998-2014.

5.6 Conclusion In addition to basic therapy with counselling, manual-based structured tCBT in an individual or group design using a validated therapy manual (e.g., according to Kröner-Herwig 1997 [125]) is available as a therapeutic

option. Regarding tinnitus distress, quality of life, and depression scores, this approach has been proven to be highly effective and, therefore, can be recommended. In order to prepare for structured tCBT, the patients have to be guided by counselling and should not be left alone with their illness. It needs to be conveyed to the patient that gradual habituation to the tinnitus is often achievable using tCBT. Furthermore, the patient needs to be attuned to the need that he or she must be prepared to take an active, extensive, and cooperative role in the therapy. A drug therapy targeting the symptoms of tinnitus is not available. The following measures are useful:

• Basic therapeutic measures with tinnitus counselling should be carried out (Appendix 1). For the treatment of concomitant hearing loss, hearing therapy measures can be recommended.

• Due to the high level of evidence, structured tCBT using a validated therapy manual is strongly recommended: this should be applied.

• Comorbidities should also be treated (see Table 1), and if indicated with drugs. • When needed, particular attention should be paid to therapies for coping with anxiety, if necessary

with pharmaceutical support. • When needed, particular attention should be paid to therapies for coping with depression, if

necessary with pharmaceutical support • If the individual situation demands it, psychiatric treatment should also be given.

With simultaneous deafness or hearing loss bordering on deafness, a cochlear implant may be indicated. For audio therapeutic measures, transcranial magnetic or direct current stimulation, specific forms of acoustic stimulation (noisier, masker, "notched music", "coordinated reset"), and specific music therapeutic measures, the recommendations remain an open issue and cannot be made at this juncture given the inadequate body of data supporting their use.


Polypragmatic tinnitus treatments involving therapeutic procedures with no evidence-based effectiveness are to be rejected.

tCBT may be carried out in appropriately qualified facilities, such as medical practices, hospitals, or spa and rehabilitation centres. This can be administered as individual or group therapies, or a mixture of the two. Any comorbidities the individual may be suffering from can then be dealt with at the same time. If a patient with severe decompensation due to tinnitus-induced helplessness cannot be treated on an outpatient basis, an appropriate inpatient treatment can be indicated if the patient also suffers from a serious psychiatric comorbidity.

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Appendix 1 Counselling for tinnitus

8

In the initial consultation with the patient, the doctor should not lead with his questions, but should instead provide the patient an opportunity to spontaneously and extensively talk about their discomfort, their conceptions of the disease, and their fears. Ideas about the disease on the part of the patient are often inaccurate, but the disease can sometimes be perceived as extremely threatening by the patients. Their ideas about the disease and any assumptions of imminent danger should be taken very seriously. Important advice about how to commandeer the consultation can be found in the German S3 guideline on dealing with patients suffering from non-specific, functional, and somatoform body complaints. The discussions between the doctor and patient should address the patient’s living circumstances (occupation, leisure time, rest, falling to sleep, stress/tension scenarios) when the tinnitus is perceived as a nuisance, as well as the contexts in which the patient considers it to be bearable (situations where they hear other noise, music, ocean waves, fountains, machine noise, when they are generally distracted, when they use a hearing aid, when they consume alcohol, etc.). During the medical consultation, the following messages are particularly important to convey:

• There are noises in the ear that many of us, even the doctor, do not perceive. • There are physiological sounds, such as swallowing, which are usually louder than

the subjective tinnitus but that are not perceived. • The patient suffers from ear noises and the doctor fully believes that this is the case. • Help for the sick is almost always possible; a cessation of chronic ear noise is

possible even after many years. In the chronic stage, the goal of "eliminating tinnitus" is counterproductive. The primary objective should be habituation that paves the way towards completely "forgetting" the tinnitus.

• If the condition deteriorates, treatment options are available. • The doctor has to convey to the patient that he/she can do something so that the

tinnitus no longer torments them. The patient is not helpless. There are ways the patient can modify his/her environment so that the interference caused by the tinnitus is reduced. The patient’s own opinions towards the tinnitus can be changed so that the "sting" can be taken away by assuming a calm and relaxed attitude. This can also be trained, whereby tCBT can assist the patient so that he/she is then able to displace the tinnitus from the centre of his/her attention, and he/she has more room to focus on other positive aspects of life.

• Education to allow an understanding of the correct disease model: From his examination, the doctor can inform the patient that the noise is not an expression of a brain tumour or other nasty ailment, and that there is no danger to his or her life, no risk of apoplexy, and no risk of another brain disorder. Instead, the doctor can say that the noises occur as a result of a hearing impairment or damage to the auditory system. During the consultation, the patient will be presented with the basics of the anatomy and physiology of the auditory system, in the best case with the help of figures. Building on this, the patient will be presented his individual tinnitus disease model, which will include his/her history, findings, and information about how his/her symptoms arise and how they are maintained. Thus excluding a dangerous disease of the ear or brain. The patient can then eliminate anxieties he/she may have.

• Advice for sound enrichment: The focus here is to prevent periods of silence. Several methods are available to pleasantly enrich sound in one’s own everyday

8 Randomised, controlled, also investigated in Zenner 2013 [271]


environment. Irritating or disturbing sounds must always be avoided in this process. In most cases, the best sound signals are sounds from nature. In summer, one can simply open a window when the sounds surrounding the home are perceived by the patient as pleasant. Most people find sounds from nature pleasant and relaxing. Patients with tinnitus (and sometimes also hyperacusis) find woods, gardens, or beaches to be pleasant places and also like to hear the rain and wind. For other patients, the pleasant sound of a fan or table fountain may be more appropriate. Sustainable sound enrichment often means several hours of listening to CDs that produce white noise, physiological noise, or volume modulated noise, such as wave noise (a volume that should not lead to a suppression of the tinnitus, but should just be pleasantly audible).

• If necessary, advice on hearing aids, assessment of communication impairment, and differentiation of symptom areas: Complaints about impaired communication are almost always attributable to a parallel existing hearing loss and not the tinnitus. If a hearing impairment is also present, the early acceptance of a hearing aid can often reduce the sensitisation to tinnitus. One of the mechanisms is probably the diversion of more attention towards speech signals at the same time when attention is being diverted from the tinnitus.

Appendix 2 Procedure for creating consensus 1. Introduction The development of this guideline was preceded by the recommendations of an expert group [105], as well as a

consensus-driven S1 guideline (AWMF guideline 017/064 1998 revised 2010). In agreement with the AWMF classification, the previous guideline recommendations have been reviewed and revised on the basis of systematic literature reviews and evaluations. This process was based on the rules of the AWMF (http://www.awmf-leitlinien.de), as well as the requirements formulated in the German instrument for methodological guideline appraisal from the AWMF and the ÄZQ (Delbi, http://www.delbi.de ). 2. Methodological rigour: research, selection, and evaluation of scientific evidence (evidence basing) 2.1 Formulation of key questions (See DELBI criterion 2) According to the AWMF requirements, a first original text draft was discussed in a nominal group process, and clinical questions and search terms formulated on this foundation. 2.2 Use of existing guidelines on the subject

Based on the clinical questions and search terms, a systematic search for international guidelines was carried out in Google and the database of the Guidelines International Network (http://g-i-n.net from 30/01/2012 – 07/27/2014), the National Guideline Clearinghouse (USA), and in other databases mentioned below.

Search term: "Tinnitus Guideline", "Guideline Tinnitus <country name>", restrictions: publication / revision 2000-2014, in German or English.

Table 28: Search phrase guidelines in Google and the database of the Guidelines International Network (http://g-i-n.net; time-point: last 07/27/2014).

The choice of possible reference guidelines was based on the methodological quality criteria summarised in the DELBI instrument. Special emphasis was placed on systematic development and traceable evidence based on the recommendations that were made (DELBI domain 3).

http://www.delbi.de/


USA 1: American Acad. Audiol. (October 18th, 2000, www.audiology.org) Excerpts

9

Tinnitus Patient Management Procedures

Similar to the evaluation process, the treatment of patients with tinnitus is most likely to succeed when a multidisciplinary approach is employed. While it is true that, at this time, there is no cure for most cases of tinnitus, it is not true that “there is nothing that can be done about it". A number of treatment approaches that can be performed by audiologists have been described with various degrees of reported success. They are listed below (in alphabetical order) along with a brief description:

• Counselling: A trained professional counsellor can be very helpful whenever the tinnitus becomes problematic. Counselling should be considered both as a primary approach, when appropriate, and as an adjunctive approach to all treatment strategies. Counselling consists of gathering data through careful listening, making adjustments in one's strategies based on that knowledge, and conveying information. Thus, it serves both a diagnostic and therapeutic function.

• Cognitive Behavioural Therapy. One type of counselling that may be successful in helping people cope with tinnitus is cognitive behavioural modification therapy. This approach can help persons identify the way they react to their tinnitus and learn new responses, thereby minimising the negative thoughts and behaviour patterns that are associated with tinnitus

• Habituation & Tinnitus Retraining Therapy. Tinnitus Retraining Therapy is a method developed to facilitate habituation to tinnitus. It combines sound enrichment therapy with directive counselling. Sound is employed to reduce the contrast between silence or ambient noise and the perception of the tinnitus. It may be in the form of environmental sounds, amplification, or broadband sound generating devices. A reduction of the perception of the tinnitus (but not complete obliteration of it) is considered essential to the process of habituation. Counselling and education serve to demystify tinnitus, providing the patient with an intellectual and emotional framework in which habituation can occur.

• Hearing Aids & Tinnitus Instruments. For individuals with hearing loss, environmental sounds may be inadequate in themselves to afford relief. However, amplifying them with the assistance of hearing aids may provide enough background stimuli to give tinnitus relief, while simultaneously enhancing the individual's listening and communication abilities. If hearing aids alone are inadequate, tinnitus instruments may be of help. Tinnitus instruments are devices that provide amplification and add the option of an independently controlled broadband sound generator.

• Maskers & Home Masking Devices. Maskers are used to cover-up the tinnitus perception with a

competitive signal that either partially or complete competes with or conceals the tinnitus. This can be achieved by a number of methods, ranging from environmental masking to ear-level worn sound generators. Also, there are commercially available recordings of a wide range of sounds that can provide complete or partial masking. In addition to their masking effect, these sounds may assist in relaxation.

• Self-help and Support/Education Groups. Some people find help, stay informed on the latest information, and share treatment experiences by talking to others with similar problems. These groups should be facilitated, or at least attended, by an audiologist or a psychologist (to prevent misinformation from being conveyed) and may include lectures from a variety of related disciplines.

• Stress Management. Stress can aggravate tinnitus, and tinnitus can be very stressful. There are many procedures that can be helpful in learning to manage stress. Biofeedback-assisted relaxation is one technique that people can learn to control breathing, muscle tension, and heart rate. Other methods of stress reduction include yoga, meditation, self-hypnosis, and exercise.

• There is no evidence to support the effectiveness of alternative treatments such as acupuncture, homeopathy, and herbal remedies, such as ginkgo biloba.

USA 2: American Speech-Language-Hearing Ass.: no therapeutic recommendation

USA 3: American Academy of Otolaryngology, Head and Neck Surgery 2014 (Tunkel et al. 2014 [252])

Excerpts

10

• Education and counselling: Clinicians should educate patients with persistent, bothersome tinnitus about management strategies. Recommendation based on studies of the value of education and

9 Selected quotes

10 Selected quotes

http://www.audiology.org/


counselling, with a preponderance of benefit over harm. Action Statement Profile

Quality improvement opportunity: To address potential under-utilisation of education and counselling by clinicians who manage patients with persistent bothersome tinnitus. To bring awareness of available management strategies to the patient.

• Hearing aid evaluation: Clinicians should recommend a hearing aid evaluation for patients with hearing loss and persistent, bothersome tinnitus. Recommendation based on observational studies with a preponderance of benefit over harm.

• Sound therapy: Clinicians may recommend sound therapy to patients with persistent, bothersome

tinnitus. Option based on RCTs with methodological concerns, with a balance between benefit and harm.

• Cognitive behavioural therapy: Clinicians should recommend CBT to patients with persistent, bothersome tinnitus. Recommendation based on RCTs, with a preponderance of benefit over harm.

• Medical therapy: Clinicians should not routinely recommend antidepressants, anticonvulsants, anxiolytics, or intratympanic medications for a primary indication of treating persistent, bothersome tinnitus. Recommendation (against) based on systematic reviews and RCTs with methodological concerns, with a preponderance of benefit over harm.

• Dietary supplements: Clinicians should not recommend ginkgo biloba, melatonin, zinc, or other

dietary supplements for treating patients with persistent, bothersome tinnitus. Recommendation (against) based on RCTs and systematic reviews with methodological concerns, with a preponderance of benefit over harm.

• Acupuncture: No recommendation can be made regarding the effect of acupuncture in patients with

persistent bothersome tinnitus. No recommendation based on poor quality trials, no benefit, and minimal harm.

• Transcranial magnetic stimulation: Clinicians should not recommend TMS for the treatment of patients with persistent, bothersome tinnitus. Recommendation (against) based on inconclusive RCTs.

USA 4: National Institute on Deafness and Other Communication Disorders (NIDCD) [URL:

http://www.nidcd.nih.gov/health/hearing/pages/tinnitus.aspx accessed 18th November 2014] Excerpts

11

Treatment depends on the cause. Treatments may include hearing aids, sound-masking devices, medicines, and ways to learn how to cope with the noise.

• Hearing aids often are helpful for people who have hearing loss along with tinnitus. Using a hearing aid adjusted to carefully control outside sound levels may make it easier for you to hear. The better you hear, the less you may notice your tinnitus. Read the NIDCD fast sheet Hearing Aids for more information.

• Counselling helps you learn how to live with your tinnitus. Most counselling programmes have an educational component to help you understand what goes on in the brain to cause tinnitus. Some counselling programmes also help you change the way you think about and react to noticeable ear noise, to help you relax during the day, or to fall asleep at night.

• Wearable sound generators are small electronic devices that fit in the ear and use a soft, pleasant sound to help mask the tinnitus. Some people want the masking sound to totally cover up their tinnitus, but most prefer a masking level that is just a bit louder than their tinnitus. The masking sound can be a soft „shhhhhhhhhhh," random tones, or music.

• Table-top sound generators are used as an aid for relaxation or sleep. Placed near your bed, you can programme a generator to play pleasant sounds, such as waves, waterfalls, rain, or the sounds of a summer night. If your tinnitus is mild, this might be all you need to help you fall asleep.

• Acoustic neural stimulation is a relatively new technique for people whose tinnitus is very loud or won't go away. It uses a palm-sized device and headphones to deliver a broadband acoustic signal embedded in music. The treatment helps stimulate change in the neural circuits in the brain, which eventually desensitises you to the tinnitus. The device has been shown to be effective in reducing or eliminating tinnitus in a significant number of study volunteers.

• Cochlear implants are sometimes used in people who have tinnitus along with severe hearing loss. A cochlear implant bypasses the damaged portion of the inner ear and sends electrical signals that directly stimulate the auditory nerve. The device brings in outside sounds that help mask tinnitus and stimulate change in the neural circuits. Read the NIDCD fact sheet Cochlear Implants for more information.

• Antidepressants and anti-anxiety drugs might be prescribed by your doctor to improve your mood and help you sleep.

• Other medications may be available at drugstores and on the Internet as an alternative remedy for tinnitus, but none of these preparations have been proved to be effective in clinical trials.

11 Selected quotes

http://www.nidcd.nih.gov/health/hearing/pages/tinnitus.aspx


USA 5: US National Guideline Clearinghouse: no guideline for tinnitus (March 2012)

Great Britain 1: GIN.net: The search resulted in the British results mentioned below

Great Britain 2: "Clinical Guidelines" (NHS): no guideline for tinnitus

Great Britain 3: "Clinical topics" (NHS): Scenario tinnitus (the content is as given below)

Great Britain 4: Prodigy (Sowerby Centre for Health Informatics) (01/04/2010), Scenario Management Excerpts

12

Drugs no drugs

What advice can I give about using sound enrichment to reduce the impact of tinnitus? • Recommend the use of sound to reduce the intrusiveness of tinnitus in quiet environments. • This may be especially useful when the person is trying to sleep, work, or read in a quiet

environment. • Advise the person to experiment with different sounds to find what suits them best in different

situations. Options include:

Opening a window to let in sounds from the outside.

Leaving a television or radio on in the background.

Static noise from a radio that has been tuned to be between stations.

Noise from a fan.

Recorded sounds associated with relaxation (such as running water, rain, or bird song) produced by a bedside generator. Some sound generators and MP3 players can be plugged into pillow speakers, reducing the audibility of these sounds to the person's partner.

• Advise the person to experiment with the volume of sound.

Lower sound volumes that do not completely mask tinnitus may help to control the

intrusiveness of the tinnitus to an acceptable level. Some experts believe that constant exposure to a very low level of tinnitus helps the person develop habituation to their tinnitus, reducing its intrusiveness in the long term.

Higher sound volumes may completely mask tinnitus when in use, but may make the

tinnitus more noticeable for some people when the sounds are turned off.

What symptomatic treatment for tinnitus can a person expect to be offered following referral to secondary care?

• Tinnitus retraining therapy is used to reduce the impact of tinnitus and help habituation develop. It

is composed of two main elements: sound therapy and counselling.

Sound therapy involves providing a background of sound at a level just below that of the tinnitus. This is usually for 6-20 hours a day and particularly when the environment is quiet.

The sound may be provided by a portable (wearable) noise generator (previously called a masker) or a combination device that contains both a hearing aid and a sound generator.

This background level of sound reduces the intrusiveness of tinnitus without completely masking it. It is thought that by only partially masking it, habituation to tinnitus can develop.

Counselling involves:

Providing information about how tinnitus develops and how it can be influenced. Helping the person deal with any stress and other problems they may have. Identifying and dealing with any false beliefs, attitudes, or fears the person has

about tinnitus.

Scotland 1: Scottish Intercollegiate Guideline Network [URL: http://www.sign.ac.uk/ Accessed on: November 19, 2014 - no guideline for tinnitus]

Scotland 2: The Scottish Government, Audiology Services Advisory Group (ASAG): Tinnitus Guidelines: July 27, 2007 http://www.scotland.gov.uk/Topics/Health/health/audiology/Publications/Tinnitus Extracts

13

12 Selected quotes

13 Selected quotes

http://www.sign.ac.uk/

http://www.scotland.gov.uk/Topics/Health/health/audiology/Publications/Tinnitus


Techniques that should be available to the team. These are given in alphabetical rather than any other order. • Biofeedback • Cognitive Behavioural Therapy • Counselling • De-sensitisation for hyperacusis/phonophobia • Information and education for staff and patients • Neurophysiologically based management including Tinnitus Retraining Therapy • Access to clinical psychology if not part of the team • Relaxation and other anxiety management techniques • Sleep hygiene/tactics • Sound therapy (white noise generators (WNG), hearing aids) • Tinnitus group sessions

Table 29: Tinnitus guidelines (November 2014)

2.3 Systematic literature survey Based on the above-mentioned key questions and the detailed search performed according to the requirements in the tables, targeted literature surveys and evaluations were carried out. For this purpose a systematic search was carried out in PubMed and the Cochrane Library (www.ncbi.nlm.nih.gov/pubmed and www.thecochrancelibrary.com). The literature survey was last updated on 07/27/2014. In this survey, keywords ("MeSH") were favoured over free text words. The detailed search for the main literature was carried out in accordance with the search strategies stated in the evidence tables, special tables, or text for the respective therapies.

MeSH Ear, Nose, and Throat Disorders /Otorhinolaryngology Diseases (C09) o Ear Diseases (C09.218)

MeSH Neurological Disorders / Nervous System Diseases (C10) o Neurologic Manifestations (C10.597)

MeSH "tinnitus" AND (e.g. "name of a comorbidity" [MeSH] OR e.g. "name of a comorbidity" [MeSH])

Literature research: pharmacological treatment Objective: Evidence of pharmacological interventions Search: 18/04/2013-20/04/2014 Search period: 1980 to present Databases: PubMed, Cochrane Keywords: tinnitus AND randomized controlled trial

Literature research: Neuromodulation Objective: Evidence for neuromodulation in the treatment of tinnitus Search: 18/04/2013-20/04/2014 Search period: 1980 to present Databases: PubMed, Cochrane Keywords: tinnitus AND randomized controlled trial

http://www.ncbi.nlm.nih.gov/pubmed

http://www.thecochrancelibrary.com/

http://www.thecochrancelibrary.com/


Table 30: Example of a search strategy in the PubMed and Cochrane databases. Restrictions: German or English language.

2.4 Selection of evidence The evidence classification of the Oxford Centre of Evidence-based Medicine was used as the basis for presenting evidence of the key messages outlined in this report. Whenever available, RCTs were primarily used to answer therapeutic questions. In order to harmonise the classification process, most of the members of the consensus conference were schooled in this regard. 2.5 Evaluation of the evidence The quality of the studies was assessed according to three main criteria: a) Does the study adequately describe a concealed randomisation ("concealment of allocation")? b) Is the study blinded with respect to the main endpoints (if possible)? c) Were all available patients originally in the randomised group evaluated in the follow-up ("intention-to-treat analysis", ITT), and were no more than 10% of the patients from the primary analysis missing in the follow-up? Even when patients were excluded from a study due to non-compliance or the rate of drop-outs differed significantly between the two groups, the study was evaluated as being negative for the ITT principle. All systematic reviews/meta-analyses were also tested for their methodological quality. 2.6 Creation of evidence tables

The evidence tables can be found in the text above. 2.7 Consideration of benefits, side effects, and relevant outcomes Whether the number of cases and/or small differences prevented the establishment of an adequate evidence base (positive distortion, low methodological quality), despite possible significance, was taken into consideration. The effect size was also taken into account. A difference could be significant but still be so small that no clinical benefit was evident (insufficient clinical effect size). Likewise, side effects were included. Consideration was also given to group sizes, statistical tests (whether they were appropriate), conclusions, concealment of clinically relevant differences in equality, evaluation, accuracy of formulation, demonstration of safety (report on adverse events according to the CONSORT Extension for Harms, ICH-E2, ICH-E3), reproducibility (according to DIN ISO 5725), and the discussion of data from the literature. The methodological significance (methodological quality) regarding potential devaluations of significant findings, clinical effect strengths, and positive distortions were also evaluated. 2.8 Formulation of recommendations and assignment of evidence levels and/or recommendation grades

The recommendations are classified into four recommendation grades. In general, the quality of evidence (evidence level) determines the grade of recommendation. Thus, a recommendation based on a moderate level of evidence is usually associated with a “moderate” recommendation grade (Table 31).

Study quality Evidence level for effectiveness

Description of recommendation

Systematic review (meta-analysis), RCTs (therapy), or cohort studies (risk factors, diagnosis) of high quality

High Strong Recommendation

RCTs or cohort studies of limited quality Moderate Recommendation

RCTs or cohort studies of poor quality, all other study designs, expert opinion

Weak Recommendation open

Negative results None No recommendation

No results None No recommendation

Table 31: Evidence level and recommendation grade. The evidence level is based on the effectiveness according to guideline methodology (http://www.leitlinien.de/leitlinienmethodik/leitlinien-glossar/glossar/Wirksamkeit).

When determining the grades of recommendation in a formal consensus procedure, the directness/external validity and homogeneity of the overall evidence, the benefit-risk assessment, the clinical relevance of the efficacy endpoints, the feasibility and applicability of providing that form of treatment, and the ethical obligations were taken into consideration in addition to the quality of the underlying evidence.

http://www.leitlinien.de/leitlinienmethodik/leitlinien-glossar/glossar/Wirksamkeit


Because of the above-mentioned consensus issues, an appreciation or devaluation of the recommendation in relation to the evidence level was sometimes carried out. The justifications for such deviations can be found in the comments contained within the respective evidence table. 3.0 Formal consensus building: procedure and implementation The consensus building process proceeded with the following major steps: Consistent with the specifications of the AWMF, the guideline group was assembled in a multidisciplinary manner and representative of its target audience. The project was publicly announced via registration with the AWMF Register on the Internet (http://www.awmf-leitlinien.de, AWMF Register number 017/064) in order to allow all interested parties to participate and/or comment. The participating institutions and interest groups involved delegated members or nominated expert appraisers. During a meeting convened on 22/11/2010, the representativeness of the group for developing the guidelines was once again evaluated by the provisional guideline group, and in a subsequent nomination process further interest groups were invited. The steering committee was established. The steering committee was tasked to ensuring that methodological regulations were implemented, processing thematic issues, supporting the substantive work of the experts, collating and editing the text drafts prepared by the experts and interest groups, and preparing draft resolutions during the steps taken to build consensus and adopt the guideline content. For these purposes, a first meeting of the steering committee was convened on 13/04/2011. In addition, a first draft was prepared consistent with AWMF regulations as part of a nominal group process, and clinical questions and search terms were formulated. Subsequently, a structured consensus building conference was moderated by the coordinator and attended by the vast majority of the conference members. An extensive Delphi procedure was also initiated. By mutual agreement, the co-ordinator was then appointed by the members of the conference as moderator and was an independent and neutral individual. During the consensus-building conference, after all the parties completely read the existing draft, it was critically discussed, and from this procedure work was then delegated to numerous conference members. The subsequent Delphi procedure involved more than 20 rounds

14 with varying involvement of the conference members depending on their

particular expertise. Written comments and suggestions for amendments were generally reported back to the members by the coordinator in anonymised form. The final version of the entire text was agreed upon by consensus within the guideline group as the Delphi procedure demanded. The moderator was not entitled to vote. The recommendations were adopted overwhelmingly with a "strong consensus" (approval by > 95% of participants). With text passages for which only a reduced level of consensus could be achieved (approval by > 75% of participants) are outlined below. The representatives of the DG PPN found the following points for which a strong consensus could not be achieved: (1) Already with acute tinnitus there are often alterations in the central nervous system, both in animal experiments (Middleton, Tzounopoulos 2012) and in humans (Ortmann et al. 2011). (2) Every perception represents a demand on the central nervous system, the distinction between tinnitus with and without centralisation is not meaningful and there would be no clinical, neurophysiological, or imaging criteria which could allow such a distinction. (4) This should be deleted: "For the frequently detectable, also unilateral hearing loss as well as with primarily central or psychogenically incurred hearing loss, a meta-analysis from 2010 presented weak evidence that hearing therapeutic measures including auditory or audio therapy are effective (Hoare et al. 2010 [97])." (5) One should refrain from using terms such as "desensitisation" and "habituation". Otherwise, one would also have to list features of other types of CBT, including "acceptance", "commitment", "relaxation", "mindfulness", "cognitive restructuring", etc. (6) For internet-based behavioural therapy, the published literature suggests a comparable efficacy with classical behavioural therapy concepts (Jaspers et al. 2014). 4.0 External appraisal and adoption 4.1 External appraisal

14 The creation of the guidelines from the first text draft through the conferences, Delphi rounds, and expert

appraisals to the final document comprised a total of 36 rounds.

http://www.awmf-leitlinien.de/


The consented draft guidelines were submitted to the boards of the participating medical societies and patient organisations for a possible commissioning of scientists to carry out external appraisals. In this part of the procedure, the German Society of Psychology (DGMB), the German Society of Audiology, the German Professional Association of Otolaryngologists (BVHNO), and the German College of Psychosomatic Medicine (DKPM) were also involved. One of the boards appointed the expert appraiser named in Chapter 1b. The expert opinions were taken into consideration in a final editing process. 4.2 Adoption by the boards of the publishing professional societies/organisations The consented draft guidelines were submitted to the boards of the participating medical societies and patient organisations for a final assessment. In this part of the procedure, the German Society of Psychology (DGMB), the German Society of Audiology, the German Professional Association of Otolaryngologists (BVHNO), and the German College of Psychosomatic Medicine (DKPM) were also involved. The overall result was a consensus. Objections on the part of the participating boards, councils, or patient organisations have not been received. 5.0 Editorial independence 5.1 Financing of the guideline The guidelines were prepared in an editorially independent manner. Travel costs were partly borne by the delegating societies or associations. The DGHNO-KHC and University of Frankfurt / M provided meeting rooms. We are very grateful to the authors, reviewers, and participants in the consensus process who were working in a purely voluntary capacity. 5.2 Presentation and handling of potential conflicts of interest In order to determine any conflicts of interest, written declarations were requested on the AMWF form. They were then evaluated by the coordinator. The declaration by the coordinator was evaluated by the legal department of the University Hospital of Tuebingen. Here, no conflicts of interest could be identified among the members and the coordinator of the consensus conference. 6.0 Distribution and implementation The guidelines will be provided free of charge as a long version on the website of the AWMF. In addition, they shall also be published in the following formats:

as a long version in a peer-reviewed journal as a short version, e.g., in the Deutsches Ärzteblatt as a short discipline-specific version in appropriate publications of professional associations as a version in English to be made available on the Internet (Guidelines International Network, GIN,

www.gin.net ) 7.0 Duration of validity and updating procedure By February 2020 at the latest a full revision shall be carried out. The contact partner for this shall be the guideline coordinator of the council of the DG ENT KHC (German Association of Otorhinolaryngology and Head and Neck Surgery). Creation date: February 2015 Next revision planned: February 2020

http://www.g-i-n.net/

http://www.g-i-n.net/


Appendix 3 Statements on conflicts of interest: Tabulated summary

Guidelines Coordinator: Prof. Dr. Hans-Peter Zenner Guideline: Chronic tinnitus Registration No: 017/064

Wolfgang Delb

Christian Gerloff

Gerhard Goebel

Gerhard Hesse

Burkard Jaeger

Birgit Kröner-Herwig

Berthold Langguth

Ingrid Peroz

Regina Trollmann

Hans-Peter Zenner

1 Consultant or appraiser activities or paid work on a scientific advisory board of a company in the healthcare industry (e.g., pharmaceutical industry, medical device industry), a commercially oriented contracted institution, or an insurance company

no Bayer Vital, Boehringer Ingelheim, EBS Technologies, Silk Road Medical

no no no no Antitony no no Patient appraisals for insurance companies (life insurance and private pension plans, liability insurance, etc.)

2 Fees for lectures and training activities or paid authorships or co-authorships commissioned by a company in the healthcare industry, a commercially oriented contracted institution, or an insurance company

no Bayer Vital, Boehringer Ingelheim, Biogen Idec, ev3 / Covidien, GlaxoSmithKline, Grifols, Inomed Lundbeck, Nexstim Pfizer Sanofi Aventis, UCB

yes 2x Lecture fee

Sanofi / Aventis (diabetes preparations) 2013 Grünenthal (analgesics) 2013

no no no no no

3 Financial assistance (funding) for research projects or direct financing of staff in the facility by a company in the healthcare industry, a commercially oriented contracted institution, or an insurance company

no Merz Pharma ceuticals, Allergan, Novartis, NeuroConn

no no no no Otonomy Siemens

no no Joint research project of the BMFT to develop a middle ear implant

4 Ownership interest in drugs/medical devices (e.g., patent, copyright, licensed sales)

no no no no no no Cyclobenzcaprine no no No patent with validity concerning tinnitus


5 6

Ownership of shares, stocks, or funds in companies of the healthcare industry

no no no no Unknown (funds) probably none

no no no no no

Personal relationship with a duly authorised officer of a company in the healthcare industry

no no no Kind no no no no no no

7 Membership in professional associations involved in the guideline’s development, or groups with a mandate for the guideline’s development

DGPP, DGA

DGN (Member of the Guideline Committee) BDN (Member of the Board) DGNI DSG DGSM DGKN

yes HNO-BV DGHNO

Yes, as a Guideline Member for the DKPM

no DGPPN DGHP

no LL officer of the GNP

German Association of Otorhinolaryngology (DGHNO)

8 Political, academic (e.g., membership of certain "schools"), scientific, or personal interests that could justify possible conflicts

no no yes no no no Foundation Tinnitus Research Initiative

no no no

9 Current employers, relevant former employers during the past 3 years

Self-employed in a private practice, University Hospital Heidelberg

University Hospital Hamburg -Eppendorf

Schön Klinik Prien; Retired since 1/1/2013

Tinnitus Clinic

Medical University of Hanover

no Medical institutions of the district of the Upper Palatinate

no no University of Tuebingen

* Enter: No / Yes


Creation date: 05/1998 Revision of: 02/2015 Next Revision planned: 02/2020

The "guidelines" of the Scientific Medical Societies are systematically developed aids for physicians

to help them make decisions in specific situations. They are based on current scientific knowledge and

procedures that have proven themselves in practice, and they ensure greater safety in medicine.

However, they should also take into account the economic aspects of treatment. The "guidelines" are

not legally binding for doctors and, therefore, do not have any relieving or encumbering effect on

legal liability.

The AWMF has prepared and published the guidelines of professional societies with the greatest care.

Nevertheless, the AWMF cannot assume responsibility for the accuracy of the content. When

considering dosages in particular, the recommendations of the manufacturers must always be

followed!

© German Society of Otorhinolaryngology and Head and Neck Surgery Authorized for electronic publication: AWMF online

Documents

AWMF-Register No. 017/064 Class.: S3€¦ · German S3 guideline Ol 7/064: Chronic tinnitus Current revision: 02/2015 published in: AWMF online The Portal For Scientific Medicine