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What’s the Buzz? Treatment Strategies in Chronic Subjective Tinnitus
CE/CME No: CR-1810
PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.
EDUCATIONAL OBJECTIVES
• Distinguish primary tinnitus from secondary tinnitus.
• Understand and implement a full clinical evaluation of tinnitus, including imaging studies when appropriate.
• Discuss expectations regarding treatment options and realistic outcomes of currently recommended therapy.
• Direct patients to specialist care for cognitive behavioral therapy or tinnitus retraining therapy.
• Know when pharmacotherapeutic intervention is indicated.
FACULTY
Wendy Gillian Ross practices urgent care medicine in Lake Grove, New York, and primary care in Patchogue, New York. Randy Danielsen is Professor and Dean, Arizona School of Health Sciences, and Director, Center for the Future of the Health Professions, both at A.T. Still University, in Mesa, Arizona. He is Physician Assistant Editor-in-Chief of Clinician Reviews.
The authors have no financial relationships to disclose.
ACCREDITATION STATEMENT
This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid through September 30, 2019.
Article begins on next page >>
Tinnitus can be a debilitating condition that affects quality of life and is often not treated according to guidelines. Cognitive behavioral therapy and tinnitus retraining therapy have been successful in reducing tinnitus bother; pharmacotherapy is not widely accepted as successful, and can, in fact, be deleterious. This article describes pathophysiologic disturbances of hearing and how they relate to chronic subjective tinnitus, discusses the clinical evaluation of tinnitus as a presenting symptom, and reviews current treatments.
Primary chronic subjective tinnitus, often thought of more as a symptom than a diagnosis, affects millions of people worldwide. This troublesome condition has been chronicled as far back as the first century
It is estimated that only 20% of people who experience tinnitus actively seek treatment.2 In the United States, 2 to 3 million of the 12 million patients who do request treatment report lasting symptoms that they describe as debilitating.3 For patients who seek help, the treatment recommended by physicians is typically pharmacotherapeutic—which does not follow guidelines.4
The aim of this article is to reinforce a greater understanding of the mechanisms of tinnitus and integrate that knowledge into treatment guidelines. The article does not discuss surgical treatment of tinnitus.
DEFINITION AND CLASSIFICATION
A universal standard definition of chronic tinnitus does not exist; Trevis et al define it as a phantom sound that persists for more than three months.5 The quality and loudness of tinnitus is variable but is often described as a buzz, hiss, or ringing. Prevalence increases with age, smoking, male gender, and ethnicity, with the non-Latino white population statistically at greater risk.3 Comorbid conditions (eg, diabetes and other autoimmune diseases) are risk factors for tinnitus. A history of exposure to loud sound—occupational, environmental, or recreational—also can predispose a person to tinnitus.3
The American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) classifies tinnitus as primary (subjective) or secondary (objective). Primary tinnitus—representing the majority of cases—has no identifiable cause; there may be accompanying sensorineural hearing loss or hyperacusis. Secondary tinnitus can also be associated with sensorineural hearing loss but has an identifiable underlying cause.6 The differential diagnosis of tinnitus is listed in the Table.7
Tinnitus is further defined by its persistence. Persistent tinnitus is defined as tinnitus lasting more than six months, slightly longer than the duration offered by Trevis et al, who also define tinnitus as bothersome or non-bothersome, depending on its impact on quality of life.5,6 Causes of reduced quality of life include depression, anxiety, insomnia, and neurocognitive decline—all of which have been associated with chronic subjective tinnitus.8
Continue to: Researchers have discovered that...
Researchers have discovered that tinnitus is not simply a cochlear phenomenon. The pathology extends well beyond the auditory complex, having a deleterious effect on both the somatosensory and central nervous systems, providing some explanation for the prevalence of anxiety and depression associated with the disorder (see "Pathophysiology of tinnitus").9-17
Because of the insidious nature of tinnitus and lack of standard measures of severity, true prevalence is difficult to calculate.18
CLINICAL EVALUATION
Tinnitus can be a presenting complaint or elicited during history-taking. Symptomatic patients should receive full evaluation, including a complete physical exam, medication history, and laboratory workup.
Adverse effect of drugs
Medications that commonly cause tinnitus symptoms are NSAIDs, chemotherapeutic agents, and antibiotics (eg, macrolides and fluoroquinolones). Amiodarone, ACE inhibitors, proton-pump inhibitors, and calcium-channel blockers have also been implicated. Paradoxically, anxiolytics and tricyclic antidepressants, which are sometimes used to treat tinnitus, have been linked to causing the condition.7
Laboratory tests and imaging
Testing should include investigation for infectious disease, autoimmune disorders, and vitamin deficiency.7 According to the American College of Radiology, imaging is unnecessary in the workup of primary tinnitus. Any suspicion of a vascular cause noted on the physical exam (eg, an associated bruit or venous hum), however, should be explored with imaging. Furthermore, any case of tinnitus that lateralizes also requires additional investigation. Modalities of choice are MRI, CT, and CT angiography.19
Continue to: Referral for audiology evaluation
Referral for audiology evaluation
When no underlying pathology can be identified for tinnitus, the patient should be sent for a full audiology evaluation to screen for associated hearing loss. Discussion of audiology screening tests is beyond the scope of this article; however, testing includes otoscopy, audiography, tympanography, otoacoustic emission testing, auditory brainstem-response testing, and vestibular evoked myogenic potential testing.7
Probing nonphysical impacts
Quality of life and overall emotional wellness, including cognitive function, should be investigated in patients with tinnitus. Two questionnaires commonly used in the assessment of tinnitus bother are the Tinnitus Handicap Inventory and the Tinnitus Reaction Questionnaire.7 In a large, systematic review, Trevis et al report that “64% of studies investigating depression found an increase in depressive symptoms in people with chronic tinnitus compared to hearing control groups, and 62% of studies investigating anxiety reported significantly increased anxiety symptoms.”5
MANAGEMENT
Tinnitus management should be viewed two ways: treatment of perceived loudness and treatment of comorbid symptoms relating to tinnitus bother.6 In the same meta-analysis, Trevis and colleagues found that patients with tinnitus had higher rates of anxiety, depression, and overall decline in cognitive function, including processing speed, concentration, and sleep disorders.5 It is useful to keep this observation in mind when reviewing treatment options for tinnitus.
Five classic pharmacotherapeutic approaches to tinnitus management are
- Anticonvulsants
- Antidepressants
- Anesthetics
- Anxiolytics
- Lidocaine.
Newer medications that show some promise are N-methyl-D-aspartate (NMDA) receptor antagonists, notably neramexane. Alternative pharmaceuticals include vitamin-based treatments, cannabinoids, and herbal compounds.
Continue to: The AAOS-HNS supports...
The AAO–HNS supports nonpharmacotherapeutic treatment of tinnitus; its guidelines include a recommendation for cognitive behavioral therapy (CBT) as primary therapy.6 In addition, tinnitus-retraining therapy, tinnitus-masking therapy/sound therapy, meditation/mindfulness, and yoga all have been studied for their ability to alleviate tinnitus bother.
Pharmacotherapeutic management
Anticonvulsants have failed to provide strong evidence of usefulness in the treatment of tinnitus and are not supported by the AAO–HNS as such.6 This conclusion notwithstanding, the anticonvulsants carbamazepine and gabapentin have historically been two of the more common medications used to treat tinnitus.
Carbamazepine is a glutamate receptor antagonist that suppresses seizure activity. Based on prior research suggesting that spontaneous firing within the auditory complex is similar to seizure activity, Iranian researchers explored the hypothesis that carbamazepine might lessen tinnitus severity. Their study revealed, however, that carbamazepine did not statistically significantly reduce the severity of tinnitus, compared to placebo.20 While carbamazepine may be of limited use in the treatment of subjective tinnitus, recent literature confirms that it is not only useful, but also diagnostic, in typewriter tinnitus (ie, having a staccato quality, like the sound of typewriter keys being depressed). Typewriter tinnitus is a secondary cause of tinnitus related to disruption of the stapes in the middle ear.21
Gabapentin works by promoting gamma-aminobutyric acid (GABA) production in the brain. GABA is an inhibitory neurotransmitter, thus slowing down signals between neurons. Following on preliminary research that detected low levels of GABA in the inferior colliculus of rodents with salicylate-induced tinnitus, Aazh and colleagues conducted a double-blind study of gabapentin—and concluded that it yielded no improvement in symptoms, compared to placebo.22
Valproic acid has not been formally investigated but is commonly incorporated in the treatment of tinnitus.23 Lamotrigine has provided similarly disappointing results in the treatment of tinnitus.24
Continue to: Antidepressants and anxiolytics
Antidepressants and anxiolytics. Based on the results of their early clinical trials, Sullivan and colleagues concluded that tricyclic antidepressants produced significant improvement in tinnitus symptoms, due to the analgesic effects of these drugs. The researchers studied nortriptyline specifically; in severely depressed patients, the drug reduced the loudness of tinnitus and depressive symptoms. In non-depressed subjects, however, nortriptyline was not as efficacious.25
Selective serotonin reuptake inhibitors have not had the same success as nortriptyline. In a study of paroxetine conducted by Oishi and colleagues, there was little evidence that the drug reduced the loudness of tinnitus, although overall, it did reduce tinnitus bother and anxiety.26
Included in the category of anxiolytics, benzodiazepines have long been used to treat severe tinnitus-induced anxiety, with some success. However, as Elgoyhen and Langguth point out, studies of benzodiazepines for tinnitus have been limited in size.23
The AAO–HNS does not support routine use of antidepressants and anxiolytics for tinnitus bother.7
NMDA receptor antagonists. In a recent clinical trial, neramexane was studied for its efficacy in tinnitus. Neramexane acts at the cholinergic nicotinic and NMDA receptors in the efferent auditory system. Its complex reaction is thought to prevent transmission of unwanted sound not only to structures within the auditory system but beyond, to the medial geniculate body and lateral nucleus of the amygdala. The trial has proved some benefit concerning overall perception of tinnitus loudness; a phase 2 trial is being conducted.27
Continue to: Intra-tympanic anesthetics
Intra-tympanic anesthetics. Anesthetics, such as lidocaine, have had limited success and results have not been found to be sustained.
Alternative medical managements
Traditional Chinese herbal medications have been used for centuries and are increasingly popular in Western culture. Hilton and colleagues studied Ginkgo biloba, or maidenhair tree, a traditional Chinese herbal supplement available as an extract and as dried leaves. The main action of the extract is vasoregulatory; antiplatelet effects are also seen. Adverse effects include gastrointestinal upset and headache. In a systematic review, Hilton and colleagues concluded that Ginkgo did not reduce overall tinnitus loudness or severity; the review was limited, however, by the fact that only two studies met criteria for inclusion.28
Vitamins, lipoflavinoids, zinc, manganese, and melatonin are all supplements marketed to improve tinnitus symptoms. However, a cross-sectional study confirmed prior research that did not show any benefit from the use of these supplements.29
Cannabinoids are being studied for their proposed antiepileptic effects. There is a popular misconception of Cannabis as a singular chemical when in fact, it is a plant that contains hundreds of chemicals that each act differently on the brain. In a review, Smith and Zheng30 explain that two cannabinoid receptors, CB1 and CB2, are represented, and exert their effects, in different areas of the brain. CB1 receptors block calcium influx in presynaptic terminals, resulting in an inhibitory effect on neurotransmitter release.
CB1 receptors have been found in the dorsal cochlear nuclei, prompting research interest in how cannabinoids affect neurotransmission of unwanted sounds of tinnitus. To date, however, there are conflicting data concerning the benefit of cannabinoids and tinnitus. In fact, Smith and Zheng state that some data suggest that cannabinoids might make tinnitus worse.30
Continue to: Nonpharmacotherapeutic management
Nonpharmacotherapeutic management
Cognitive behavioral therapy. Conceptualized by Aaron T. Beck in the 1960s, cognitive behavioral therapy (CBT) is the leading recommendation made by the AAO–HNS in its tinnitus treatment guidelines.6 Beck’s work centered on the idea that behaviors are modifiable thoughts, through analysis of past experiences and assumptions based on those experiences. By understanding the core belief that a patient attaches to a feeling, Beck hypothesized that behaviors or responses to those feelings could be changed; this is accomplished through discussion to dispel unwarranted fears and by teaching coping mechanisms, such as relaxation. The idea behind CBT in the management of tinnitus is clear: The sound cannot be eliminated, but the patient’s response to the sound can be modified. Ultimately, through this modified response or habituation, the patient can relax and live with the sound.31
Since anxiety, depression, and insomnia are common comorbidities of tinnitus, a psychologic approach remains in the forefront of treatment recommendations. Hoare and colleagues reported that in “a meta-analysis of 10 randomized trials evaluating different forms of CBT (by the therapist and over the Internet), CBT improved tinnitus symptoms compared to non-CBT controls.”7
Tinnitus retraining therapy (TRT) is another form of habituation therapy, introduced by Jastreboff in the 1990s. His work furthered the idea that tinnitus could be reframed, as it is in CBT. Simply, he proposed that systems outside the auditory complex—namely the autonomic nervous system and the limbic system—respond to the signal produced by damaged hair cells in the cochlear nuclei. TRT retrains connections to block or ignore these signals.13 Unlike CBT, the aim of TRT is to eliminate the perception of sound.
By educating patients about the physiologic mechanisms of tinnitus, TRT reduces patient anxiety related to the sound. The process of habituation follows counseling. To accomplish this, the patient wears a sound generator, similar in appearance to hearing aids, using broadband noise. The sound does not mask the tinnitus but closes the gap between silence and the perception of tinnitus. The sound generator is worn for six hours daily for approximately 12 months.
Multiple studies have employed Jastreboff’s original technique, including a clinical trial by Bauer and colleagues. The published outcome of this study confirmed that patients experienced a positive and lasting effect with TRT.32 In addition, a small study of TRT conducted by Barozzi and colleagues, using different colors of sound (ie, how the frequency of a given sound corresponds to the light-wave frequency of a particular color), found statistically significant improvement. Allowing patients to pick a sound that they found more pleasant increased the effectiveness of the treatment.33 (Patients can learn more about TRT by visiting www.tinnitus-pjj.com, hosted by tinnitus researcher Pawel J. Jastreboff.)
Continue to: Alternative nonmedical therapies...
Alternative nonmedical therapies have become popular; they include meditation, yoga, physical therapy, mindfulness, and tinnitus-masking treatment with sound.
Results of a study of yoga and meditation showed that patients felt more relaxed, but that these interventions had no effect on the severity of tinnitus. The principle behind yoga practice, according to Köksoy and colleagues, is that the discipline is thought to affect the limbic system by deactivating the sympathetic response to stimulation from surrounding sounds. In addition, Köksoy states, other researchers have provided evidence that yoga increases circulating levels of antioxidants, which in turn reduce oxidative stress.34
Particularly among members of the millennial generation, mindfulness has become a buzzword. The practice refers to a “method for facing, exploring, and alleviating suffering by relating to present experiences.”35 Roland and colleagues conducted a clinical trial of mindfulness practiced by a cohort of patients with bothersome tinnitus; results were based on scores gleaned from standard rating scales (eg, Global Bothersome Scale, Cognitive and Affective Mindfulness Scale-Revised, Cognitive Failures Questionnaire, Tinnitus Handicap Inventory, and Tinnitus Functional Index). Evaluated before and four weeks after cessation of therapy, subjects reported that tinnitus bother was reduced, but none showed statistically significant improvement in depression, anxiety, or cognitive ability.35
Used for more than 40 years, sound-based therapy has been discussed in conjunction with TRT.36 It is recognized as an approved but optional treatment by the AAO–HNS. In response to a 2010 study by Hobson that used sound-based therapy alone for tinnitus, Tunkel and colleagues cautioned that the modality showed little benefit. The major downside to acoustic therapy, according to the AAO–HNS clinical guidelines, is cost and patients’ excessive expectation of effectiveness.6
According to the AAO–HNS, repetitive-transcranial magnetic stimulation is not supported as a valid treatment for tinnitus because it can lead to seizures in patients who are taking medication that lowers the seizure threshold or who have a secondary cause of tinnitus, such as a tumor—therefore creating risk that outweighs any benefit.6
Continue to: CONCLUSION
CONCLUSION
For a large percentage of the population, chronic subjective tinnitus is a significant variable in the evaluation of quality of life. The condition is not completely understood and often displays features unique to the individual. Much of the initial response to research linking tinnitus with shared pathways typical for chronic pain, anxiety, and depression has resulted in pharmacotherapeutic management that is not always warranted—or successful.
Clinical research into the pathophysiology of tinnitus is providing a better understanding of the neurophysiologic mechanisms that underpin the science of chronic tinnitus. With this information, researchers can one day design medical management that targets specific receptors, resulting in greater management success.
The psychologic impact of tinnitus cannot be underestimated. When almost one-third of patients complain of debilitating symptoms that can also result in neurocognitive decline, tinnitus becomes a condition that cannot be ignored. Guidelines set forth by the AAO–HNS state that CBT and TRT offer some reprieve from symptoms and teach patients habituation without further damage to hearing. The use of broad-based sound generators has been well established as a useful management tool, although it is not curative.
The limitations of some studies that reviewed alternative medicines include small sample size and difficulty comparing research analysis because of disparities in tinnitus rating scales. Also, age bias, comorbid conditions, and study drop-out rates affected overall statistical significance of some studies. Additional, high-quality research is warranted in this area.
Continue to: Prevention of tinnitus...
Prevention of tinnitus through education on hearing loss and its causes should be regarded as implicit; occupational noise and recreational use of music devices put people at heightened risk for hearing loss and tinnitus. Information and open discussion that include the discovery of tinnitus symptoms during routine physical examination are recommended.
Last, providers who adhere to recognized guidelines will aid patients in coping with the challenges that tinnitus presents. As research continues to unravel the complex interaction between neurons, medical science is hopeful that curative treatments will become available.
1. Maltby MT. Ancient voices on tinnitus: the pathology and treatment of tinnitus in Celsus and the Hippocratic Corpus compared and contrasted. Int Tinnitus J. 2012;17(2):140-145.
2. Wolever RQ, Price R, Hazelton GA, et al. Complementary therapies for significant dysfunction from tinnitus: treatment review and potential for integrative medicine. Evid Based Complement Alternat Med. 2015;15:931418.
3. Shargorodsky J, Curhan GC, Farwell WR. Prevalence and characteristics of tinnitus among US adults. Am J Med. 2010;123(8):711-718.
4. Bhatt JM, Lin HW, Bhattacharyya N. Prevalence, severity, exposures, and treatment patterns of tinnitus in the United States. JAMA Otolaryngol Head Neck Surg. 2016;142(10):959-965.
5. Trevis KJ, McLachlan NM, Wilson SJ. A systematic review and meta-analysis of psychological functioning in chronic tinnitus. Clin Psychol Rev. 2018;60:62-86.
6. Tunkel DE, Bauer CA, Sun GH, et al. Clinical practice guideline: tinnitus. Otolaryngol Head Neck Surg. 2014;151(suppl 2):S1-S40.
7. Dinces EA. Treatment of tinnitus. UpToDate. April 12, 2018. www.uptodate.com/contents/treatment-of-tinnitus. Accessed September 17, 2018.
8. Gudwani S, Munjal SK, Panda NK, Kohli A. Association of chronic subjective tinnitus with neuro-cognitive performance. Int Tinnitus J. 2017;21:90-97.
9. Jastreboff PJ. 25 years of tinnitus retraining therapy. HNO. 2015;63:307-311.
10. Pujol R. Journey into the world of hearing. 2016. www.cochlea.eu/en. Accessed September 17, 2018.
11. Adjamian P, Hall DA, Palmer AR, et al. Neuroanatomical abnormalities in chronic tinnitus in the human brain.Neurosci Biobehav Rev. 2014;45:119-133.
12. Shore SE, Roberts LE, Langguth B. Maladaptive plasticity in tinnitus—triggers, mechanisms and treatment. Nat Rev Neurol. 2016;12(3):150-160.
13. Jastreboff PJ, Gray WC, Gold SL. Neurophysiological approach to tinnitus patients. Am J Otol. 1996;17(2):236-240.
14. Kaltenbach JA. Tinnitus: models and mechanisms. Hear Res. 2011;276:52-60.
15. Rauschecker JP, Leaver AM, Mühlau M. Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron. 2010;66(6):819-826.
16. Møller AR. Sensorineural tinnitus: its pathology and probable therapies. Int J Otolaryngol. 2016;2016:2830157.
17. Chen YC, Xia W, Chen H, et al. Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex. Hum Brain Mapp. 2017;38(5):2384-2397.
18. McCormack A, Edmonson-Jones M, Somerset S, Hall D. A systematic review of the reporting of tinnitus prevalence and severity. Hear Res. 2016;337:70-79.
19. Kessler MM, Moussa M, Bykowski J, et al; Expert Panel on Neurologic Imaging. ACR Appropriateness Criteria® Tinnitus. J Am Coll Radiol. 2017;14:S584-S591.
20. Gerami H, Saberi A, Nemati, S, et al. Effects of oxcarbazepine versus carbamazepine on tinnitus: a randomized double-blind placebo-controlled clinical trial. Iran J Neurol. 2012;11(3):106-110.
21. Sunwoo W, Jeon YJ, Bae YJ, et al. Typewriter tinnitus revisited: the typical symptoms and the initial response to carbamazepine are the most reliable diagnostic clues. Sci Rep. 2017;7:10615.
22. Aazh H, El Refaie A, Humphriss R. Gabapentin for tinnitus: a systematic review. Am J Audiol. 2011;20:151-158.
23. Elgoyhen AB, Langguth B. Pharmacological approaches to the treatment of tinnitus. Drug Discov Today. 2010;15:300-305.
24. Langguth B, Kreuzer PM, Kleinjung T, De Ridder D. Tinnitus: causes and clinical management. Lancet Neurol. 2013;12(9):920-930.
25. Sullivan M, Katon W, Russo J, et al. A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms. Arch Intern Med. 1993;153(19):2251-2259.
26. Oishi N, Kanzaki S, Shinden S, et al. Effects of selective serotonin reuptake inhibitor on treating tinnitus in patients stratified for presence of depression or anxiety. Audiol Neurootol. 2010;15(3):187-193.
27. Suckfüll M, Althaus M, Ellers-Lenz B, et al. A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus. BMC Ear Nose Throat Disord. 2011;11:1.
28. Hilton MP, Zimmermann EF, Hunt WT. Ginkgo biloba for tinnitus. Cochrane Database Syst Rev. 2013;CD003852. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003852.pub3/full. Accessed September 17, 2018.
29. Coelho C, Tyler R, Ji H, et al. Survey on the effectiveness of dietary supplements to treat tinnitus. Am J Audiol. 2016;25:184-205.
30. Smith PF, Zheng Y. Cannabinoids, cannabinoid receptors and tinnitus. Hear Res. 2015;332:210-216.
31. Martinez-Devesa P, Perera R, Theodoulou M, Waddell A. Cognitive behavioural therapy for tinnitus. Cochrane Database Syst Rev. 2010:CD005233. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD005233.pub3/full. Accessed September 17, 2018.
32. Bauer CA, Berry JL, Brozoski TJ. The effect of tinnitus retraining therapy on chronic tinnitus: a controlled trial. Laryngoscope Investig Otolaryngol. 2017;2(4):166-177.
33. Barozzi S, Ambrosetti U, Callaway SL, et al. Effects of tinnitus retraining therapy with different colours of sound. Int Tinnitus J. 2017;21:139-143.
34. Köksoy S, Eti CM, Karatas¸ M, Vayisoglu Y. The effects of yoga in patients suffering from subjective tinnitus. Int Arch Otorhinolaryngol. 2018;22(1):9-13.
35. Roland LT, Lenze EJ, Hardin FM, et al. Effects of mindfulness based stress reduction therapy on subjective bother and neural connectivity in chronic tinnitus. Otolaryngol Head Neck Surg. 2015;152(5):919-926.
36. Ibarra D, Tavira-Sanchez F, Recuero-Lopez M, Anthony BW. In-ear medical devices for acoustic therapies in tinnitus treatments, state of the art. Auris Nasus Larynx. 2018;45:6-12.
CE/CME No: CR-1810
PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.
EDUCATIONAL OBJECTIVES
• Distinguish primary tinnitus from secondary tinnitus.
• Understand and implement a full clinical evaluation of tinnitus, including imaging studies when appropriate.
• Discuss expectations regarding treatment options and realistic outcomes of currently recommended therapy.
• Direct patients to specialist care for cognitive behavioral therapy or tinnitus retraining therapy.
• Know when pharmacotherapeutic intervention is indicated.
FACULTY
Wendy Gillian Ross practices urgent care medicine in Lake Grove, New York, and primary care in Patchogue, New York. Randy Danielsen is Professor and Dean, Arizona School of Health Sciences, and Director, Center for the Future of the Health Professions, both at A.T. Still University, in Mesa, Arizona. He is Physician Assistant Editor-in-Chief of Clinician Reviews.
The authors have no financial relationships to disclose.
ACCREDITATION STATEMENT
This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid through September 30, 2019.
Article begins on next page >>
Tinnitus can be a debilitating condition that affects quality of life and is often not treated according to guidelines. Cognitive behavioral therapy and tinnitus retraining therapy have been successful in reducing tinnitus bother; pharmacotherapy is not widely accepted as successful, and can, in fact, be deleterious. This article describes pathophysiologic disturbances of hearing and how they relate to chronic subjective tinnitus, discusses the clinical evaluation of tinnitus as a presenting symptom, and reviews current treatments.
Primary chronic subjective tinnitus, often thought of more as a symptom than a diagnosis, affects millions of people worldwide. This troublesome condition has been chronicled as far back as the first century
It is estimated that only 20% of people who experience tinnitus actively seek treatment.2 In the United States, 2 to 3 million of the 12 million patients who do request treatment report lasting symptoms that they describe as debilitating.3 For patients who seek help, the treatment recommended by physicians is typically pharmacotherapeutic—which does not follow guidelines.4
The aim of this article is to reinforce a greater understanding of the mechanisms of tinnitus and integrate that knowledge into treatment guidelines. The article does not discuss surgical treatment of tinnitus.
DEFINITION AND CLASSIFICATION
A universal standard definition of chronic tinnitus does not exist; Trevis et al define it as a phantom sound that persists for more than three months.5 The quality and loudness of tinnitus is variable but is often described as a buzz, hiss, or ringing. Prevalence increases with age, smoking, male gender, and ethnicity, with the non-Latino white population statistically at greater risk.3 Comorbid conditions (eg, diabetes and other autoimmune diseases) are risk factors for tinnitus. A history of exposure to loud sound—occupational, environmental, or recreational—also can predispose a person to tinnitus.3
The American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) classifies tinnitus as primary (subjective) or secondary (objective). Primary tinnitus—representing the majority of cases—has no identifiable cause; there may be accompanying sensorineural hearing loss or hyperacusis. Secondary tinnitus can also be associated with sensorineural hearing loss but has an identifiable underlying cause.6 The differential diagnosis of tinnitus is listed in the Table.7
Tinnitus is further defined by its persistence. Persistent tinnitus is defined as tinnitus lasting more than six months, slightly longer than the duration offered by Trevis et al, who also define tinnitus as bothersome or non-bothersome, depending on its impact on quality of life.5,6 Causes of reduced quality of life include depression, anxiety, insomnia, and neurocognitive decline—all of which have been associated with chronic subjective tinnitus.8
Continue to: Researchers have discovered that...
Researchers have discovered that tinnitus is not simply a cochlear phenomenon. The pathology extends well beyond the auditory complex, having a deleterious effect on both the somatosensory and central nervous systems, providing some explanation for the prevalence of anxiety and depression associated with the disorder (see "Pathophysiology of tinnitus").9-17
Because of the insidious nature of tinnitus and lack of standard measures of severity, true prevalence is difficult to calculate.18
CLINICAL EVALUATION
Tinnitus can be a presenting complaint or elicited during history-taking. Symptomatic patients should receive full evaluation, including a complete physical exam, medication history, and laboratory workup.
Adverse effect of drugs
Medications that commonly cause tinnitus symptoms are NSAIDs, chemotherapeutic agents, and antibiotics (eg, macrolides and fluoroquinolones). Amiodarone, ACE inhibitors, proton-pump inhibitors, and calcium-channel blockers have also been implicated. Paradoxically, anxiolytics and tricyclic antidepressants, which are sometimes used to treat tinnitus, have been linked to causing the condition.7
Laboratory tests and imaging
Testing should include investigation for infectious disease, autoimmune disorders, and vitamin deficiency.7 According to the American College of Radiology, imaging is unnecessary in the workup of primary tinnitus. Any suspicion of a vascular cause noted on the physical exam (eg, an associated bruit or venous hum), however, should be explored with imaging. Furthermore, any case of tinnitus that lateralizes also requires additional investigation. Modalities of choice are MRI, CT, and CT angiography.19
Continue to: Referral for audiology evaluation
Referral for audiology evaluation
When no underlying pathology can be identified for tinnitus, the patient should be sent for a full audiology evaluation to screen for associated hearing loss. Discussion of audiology screening tests is beyond the scope of this article; however, testing includes otoscopy, audiography, tympanography, otoacoustic emission testing, auditory brainstem-response testing, and vestibular evoked myogenic potential testing.7
Probing nonphysical impacts
Quality of life and overall emotional wellness, including cognitive function, should be investigated in patients with tinnitus. Two questionnaires commonly used in the assessment of tinnitus bother are the Tinnitus Handicap Inventory and the Tinnitus Reaction Questionnaire.7 In a large, systematic review, Trevis et al report that “64% of studies investigating depression found an increase in depressive symptoms in people with chronic tinnitus compared to hearing control groups, and 62% of studies investigating anxiety reported significantly increased anxiety symptoms.”5
MANAGEMENT
Tinnitus management should be viewed two ways: treatment of perceived loudness and treatment of comorbid symptoms relating to tinnitus bother.6 In the same meta-analysis, Trevis and colleagues found that patients with tinnitus had higher rates of anxiety, depression, and overall decline in cognitive function, including processing speed, concentration, and sleep disorders.5 It is useful to keep this observation in mind when reviewing treatment options for tinnitus.
Five classic pharmacotherapeutic approaches to tinnitus management are
- Anticonvulsants
- Antidepressants
- Anesthetics
- Anxiolytics
- Lidocaine.
Newer medications that show some promise are N-methyl-D-aspartate (NMDA) receptor antagonists, notably neramexane. Alternative pharmaceuticals include vitamin-based treatments, cannabinoids, and herbal compounds.
Continue to: The AAOS-HNS supports...
The AAO–HNS supports nonpharmacotherapeutic treatment of tinnitus; its guidelines include a recommendation for cognitive behavioral therapy (CBT) as primary therapy.6 In addition, tinnitus-retraining therapy, tinnitus-masking therapy/sound therapy, meditation/mindfulness, and yoga all have been studied for their ability to alleviate tinnitus bother.
Pharmacotherapeutic management
Anticonvulsants have failed to provide strong evidence of usefulness in the treatment of tinnitus and are not supported by the AAO–HNS as such.6 This conclusion notwithstanding, the anticonvulsants carbamazepine and gabapentin have historically been two of the more common medications used to treat tinnitus.
Carbamazepine is a glutamate receptor antagonist that suppresses seizure activity. Based on prior research suggesting that spontaneous firing within the auditory complex is similar to seizure activity, Iranian researchers explored the hypothesis that carbamazepine might lessen tinnitus severity. Their study revealed, however, that carbamazepine did not statistically significantly reduce the severity of tinnitus, compared to placebo.20 While carbamazepine may be of limited use in the treatment of subjective tinnitus, recent literature confirms that it is not only useful, but also diagnostic, in typewriter tinnitus (ie, having a staccato quality, like the sound of typewriter keys being depressed). Typewriter tinnitus is a secondary cause of tinnitus related to disruption of the stapes in the middle ear.21
Gabapentin works by promoting gamma-aminobutyric acid (GABA) production in the brain. GABA is an inhibitory neurotransmitter, thus slowing down signals between neurons. Following on preliminary research that detected low levels of GABA in the inferior colliculus of rodents with salicylate-induced tinnitus, Aazh and colleagues conducted a double-blind study of gabapentin—and concluded that it yielded no improvement in symptoms, compared to placebo.22
Valproic acid has not been formally investigated but is commonly incorporated in the treatment of tinnitus.23 Lamotrigine has provided similarly disappointing results in the treatment of tinnitus.24
Continue to: Antidepressants and anxiolytics
Antidepressants and anxiolytics. Based on the results of their early clinical trials, Sullivan and colleagues concluded that tricyclic antidepressants produced significant improvement in tinnitus symptoms, due to the analgesic effects of these drugs. The researchers studied nortriptyline specifically; in severely depressed patients, the drug reduced the loudness of tinnitus and depressive symptoms. In non-depressed subjects, however, nortriptyline was not as efficacious.25
Selective serotonin reuptake inhibitors have not had the same success as nortriptyline. In a study of paroxetine conducted by Oishi and colleagues, there was little evidence that the drug reduced the loudness of tinnitus, although overall, it did reduce tinnitus bother and anxiety.26
Included in the category of anxiolytics, benzodiazepines have long been used to treat severe tinnitus-induced anxiety, with some success. However, as Elgoyhen and Langguth point out, studies of benzodiazepines for tinnitus have been limited in size.23
The AAO–HNS does not support routine use of antidepressants and anxiolytics for tinnitus bother.7
NMDA receptor antagonists. In a recent clinical trial, neramexane was studied for its efficacy in tinnitus. Neramexane acts at the cholinergic nicotinic and NMDA receptors in the efferent auditory system. Its complex reaction is thought to prevent transmission of unwanted sound not only to structures within the auditory system but beyond, to the medial geniculate body and lateral nucleus of the amygdala. The trial has proved some benefit concerning overall perception of tinnitus loudness; a phase 2 trial is being conducted.27
Continue to: Intra-tympanic anesthetics
Intra-tympanic anesthetics. Anesthetics, such as lidocaine, have had limited success and results have not been found to be sustained.
Alternative medical managements
Traditional Chinese herbal medications have been used for centuries and are increasingly popular in Western culture. Hilton and colleagues studied Ginkgo biloba, or maidenhair tree, a traditional Chinese herbal supplement available as an extract and as dried leaves. The main action of the extract is vasoregulatory; antiplatelet effects are also seen. Adverse effects include gastrointestinal upset and headache. In a systematic review, Hilton and colleagues concluded that Ginkgo did not reduce overall tinnitus loudness or severity; the review was limited, however, by the fact that only two studies met criteria for inclusion.28
Vitamins, lipoflavinoids, zinc, manganese, and melatonin are all supplements marketed to improve tinnitus symptoms. However, a cross-sectional study confirmed prior research that did not show any benefit from the use of these supplements.29
Cannabinoids are being studied for their proposed antiepileptic effects. There is a popular misconception of Cannabis as a singular chemical when in fact, it is a plant that contains hundreds of chemicals that each act differently on the brain. In a review, Smith and Zheng30 explain that two cannabinoid receptors, CB1 and CB2, are represented, and exert their effects, in different areas of the brain. CB1 receptors block calcium influx in presynaptic terminals, resulting in an inhibitory effect on neurotransmitter release.
CB1 receptors have been found in the dorsal cochlear nuclei, prompting research interest in how cannabinoids affect neurotransmission of unwanted sounds of tinnitus. To date, however, there are conflicting data concerning the benefit of cannabinoids and tinnitus. In fact, Smith and Zheng state that some data suggest that cannabinoids might make tinnitus worse.30
Continue to: Nonpharmacotherapeutic management
Nonpharmacotherapeutic management
Cognitive behavioral therapy. Conceptualized by Aaron T. Beck in the 1960s, cognitive behavioral therapy (CBT) is the leading recommendation made by the AAO–HNS in its tinnitus treatment guidelines.6 Beck’s work centered on the idea that behaviors are modifiable thoughts, through analysis of past experiences and assumptions based on those experiences. By understanding the core belief that a patient attaches to a feeling, Beck hypothesized that behaviors or responses to those feelings could be changed; this is accomplished through discussion to dispel unwarranted fears and by teaching coping mechanisms, such as relaxation. The idea behind CBT in the management of tinnitus is clear: The sound cannot be eliminated, but the patient’s response to the sound can be modified. Ultimately, through this modified response or habituation, the patient can relax and live with the sound.31
Since anxiety, depression, and insomnia are common comorbidities of tinnitus, a psychologic approach remains in the forefront of treatment recommendations. Hoare and colleagues reported that in “a meta-analysis of 10 randomized trials evaluating different forms of CBT (by the therapist and over the Internet), CBT improved tinnitus symptoms compared to non-CBT controls.”7
Tinnitus retraining therapy (TRT) is another form of habituation therapy, introduced by Jastreboff in the 1990s. His work furthered the idea that tinnitus could be reframed, as it is in CBT. Simply, he proposed that systems outside the auditory complex—namely the autonomic nervous system and the limbic system—respond to the signal produced by damaged hair cells in the cochlear nuclei. TRT retrains connections to block or ignore these signals.13 Unlike CBT, the aim of TRT is to eliminate the perception of sound.
By educating patients about the physiologic mechanisms of tinnitus, TRT reduces patient anxiety related to the sound. The process of habituation follows counseling. To accomplish this, the patient wears a sound generator, similar in appearance to hearing aids, using broadband noise. The sound does not mask the tinnitus but closes the gap between silence and the perception of tinnitus. The sound generator is worn for six hours daily for approximately 12 months.
Multiple studies have employed Jastreboff’s original technique, including a clinical trial by Bauer and colleagues. The published outcome of this study confirmed that patients experienced a positive and lasting effect with TRT.32 In addition, a small study of TRT conducted by Barozzi and colleagues, using different colors of sound (ie, how the frequency of a given sound corresponds to the light-wave frequency of a particular color), found statistically significant improvement. Allowing patients to pick a sound that they found more pleasant increased the effectiveness of the treatment.33 (Patients can learn more about TRT by visiting www.tinnitus-pjj.com, hosted by tinnitus researcher Pawel J. Jastreboff.)
Continue to: Alternative nonmedical therapies...
Alternative nonmedical therapies have become popular; they include meditation, yoga, physical therapy, mindfulness, and tinnitus-masking treatment with sound.
Results of a study of yoga and meditation showed that patients felt more relaxed, but that these interventions had no effect on the severity of tinnitus. The principle behind yoga practice, according to Köksoy and colleagues, is that the discipline is thought to affect the limbic system by deactivating the sympathetic response to stimulation from surrounding sounds. In addition, Köksoy states, other researchers have provided evidence that yoga increases circulating levels of antioxidants, which in turn reduce oxidative stress.34
Particularly among members of the millennial generation, mindfulness has become a buzzword. The practice refers to a “method for facing, exploring, and alleviating suffering by relating to present experiences.”35 Roland and colleagues conducted a clinical trial of mindfulness practiced by a cohort of patients with bothersome tinnitus; results were based on scores gleaned from standard rating scales (eg, Global Bothersome Scale, Cognitive and Affective Mindfulness Scale-Revised, Cognitive Failures Questionnaire, Tinnitus Handicap Inventory, and Tinnitus Functional Index). Evaluated before and four weeks after cessation of therapy, subjects reported that tinnitus bother was reduced, but none showed statistically significant improvement in depression, anxiety, or cognitive ability.35
Used for more than 40 years, sound-based therapy has been discussed in conjunction with TRT.36 It is recognized as an approved but optional treatment by the AAO–HNS. In response to a 2010 study by Hobson that used sound-based therapy alone for tinnitus, Tunkel and colleagues cautioned that the modality showed little benefit. The major downside to acoustic therapy, according to the AAO–HNS clinical guidelines, is cost and patients’ excessive expectation of effectiveness.6
According to the AAO–HNS, repetitive-transcranial magnetic stimulation is not supported as a valid treatment for tinnitus because it can lead to seizures in patients who are taking medication that lowers the seizure threshold or who have a secondary cause of tinnitus, such as a tumor—therefore creating risk that outweighs any benefit.6
Continue to: CONCLUSION
CONCLUSION
For a large percentage of the population, chronic subjective tinnitus is a significant variable in the evaluation of quality of life. The condition is not completely understood and often displays features unique to the individual. Much of the initial response to research linking tinnitus with shared pathways typical for chronic pain, anxiety, and depression has resulted in pharmacotherapeutic management that is not always warranted—or successful.
Clinical research into the pathophysiology of tinnitus is providing a better understanding of the neurophysiologic mechanisms that underpin the science of chronic tinnitus. With this information, researchers can one day design medical management that targets specific receptors, resulting in greater management success.
The psychologic impact of tinnitus cannot be underestimated. When almost one-third of patients complain of debilitating symptoms that can also result in neurocognitive decline, tinnitus becomes a condition that cannot be ignored. Guidelines set forth by the AAO–HNS state that CBT and TRT offer some reprieve from symptoms and teach patients habituation without further damage to hearing. The use of broad-based sound generators has been well established as a useful management tool, although it is not curative.
The limitations of some studies that reviewed alternative medicines include small sample size and difficulty comparing research analysis because of disparities in tinnitus rating scales. Also, age bias, comorbid conditions, and study drop-out rates affected overall statistical significance of some studies. Additional, high-quality research is warranted in this area.
Continue to: Prevention of tinnitus...
Prevention of tinnitus through education on hearing loss and its causes should be regarded as implicit; occupational noise and recreational use of music devices put people at heightened risk for hearing loss and tinnitus. Information and open discussion that include the discovery of tinnitus symptoms during routine physical examination are recommended.
Last, providers who adhere to recognized guidelines will aid patients in coping with the challenges that tinnitus presents. As research continues to unravel the complex interaction between neurons, medical science is hopeful that curative treatments will become available.
CE/CME No: CR-1810
PROGRAM OVERVIEW
Earn credit by reading this article and successfully completing the posttest and evaluation. Successful completion is defined as a cumulative score of at least 70% correct.
EDUCATIONAL OBJECTIVES
• Distinguish primary tinnitus from secondary tinnitus.
• Understand and implement a full clinical evaluation of tinnitus, including imaging studies when appropriate.
• Discuss expectations regarding treatment options and realistic outcomes of currently recommended therapy.
• Direct patients to specialist care for cognitive behavioral therapy or tinnitus retraining therapy.
• Know when pharmacotherapeutic intervention is indicated.
FACULTY
Wendy Gillian Ross practices urgent care medicine in Lake Grove, New York, and primary care in Patchogue, New York. Randy Danielsen is Professor and Dean, Arizona School of Health Sciences, and Director, Center for the Future of the Health Professions, both at A.T. Still University, in Mesa, Arizona. He is Physician Assistant Editor-in-Chief of Clinician Reviews.
The authors have no financial relationships to disclose.
ACCREDITATION STATEMENT
This program has been reviewed and is approved for a maximum of 1.0 hour of American Academy of Physician Assistants (AAPA) Category 1 CME credit by the Physician Assistant Review Panel. [NPs: Both ANCC and the AANP Certification Program recognize AAPA as an approved provider of Category 1 credit.] Approval is valid through September 30, 2019.
Article begins on next page >>
Tinnitus can be a debilitating condition that affects quality of life and is often not treated according to guidelines. Cognitive behavioral therapy and tinnitus retraining therapy have been successful in reducing tinnitus bother; pharmacotherapy is not widely accepted as successful, and can, in fact, be deleterious. This article describes pathophysiologic disturbances of hearing and how they relate to chronic subjective tinnitus, discusses the clinical evaluation of tinnitus as a presenting symptom, and reviews current treatments.
Primary chronic subjective tinnitus, often thought of more as a symptom than a diagnosis, affects millions of people worldwide. This troublesome condition has been chronicled as far back as the first century
It is estimated that only 20% of people who experience tinnitus actively seek treatment.2 In the United States, 2 to 3 million of the 12 million patients who do request treatment report lasting symptoms that they describe as debilitating.3 For patients who seek help, the treatment recommended by physicians is typically pharmacotherapeutic—which does not follow guidelines.4
The aim of this article is to reinforce a greater understanding of the mechanisms of tinnitus and integrate that knowledge into treatment guidelines. The article does not discuss surgical treatment of tinnitus.
DEFINITION AND CLASSIFICATION
A universal standard definition of chronic tinnitus does not exist; Trevis et al define it as a phantom sound that persists for more than three months.5 The quality and loudness of tinnitus is variable but is often described as a buzz, hiss, or ringing. Prevalence increases with age, smoking, male gender, and ethnicity, with the non-Latino white population statistically at greater risk.3 Comorbid conditions (eg, diabetes and other autoimmune diseases) are risk factors for tinnitus. A history of exposure to loud sound—occupational, environmental, or recreational—also can predispose a person to tinnitus.3
The American Academy of Otolaryngology–Head and Neck Surgery (AAO–HNS) classifies tinnitus as primary (subjective) or secondary (objective). Primary tinnitus—representing the majority of cases—has no identifiable cause; there may be accompanying sensorineural hearing loss or hyperacusis. Secondary tinnitus can also be associated with sensorineural hearing loss but has an identifiable underlying cause.6 The differential diagnosis of tinnitus is listed in the Table.7
Tinnitus is further defined by its persistence. Persistent tinnitus is defined as tinnitus lasting more than six months, slightly longer than the duration offered by Trevis et al, who also define tinnitus as bothersome or non-bothersome, depending on its impact on quality of life.5,6 Causes of reduced quality of life include depression, anxiety, insomnia, and neurocognitive decline—all of which have been associated with chronic subjective tinnitus.8
Continue to: Researchers have discovered that...
Researchers have discovered that tinnitus is not simply a cochlear phenomenon. The pathology extends well beyond the auditory complex, having a deleterious effect on both the somatosensory and central nervous systems, providing some explanation for the prevalence of anxiety and depression associated with the disorder (see "Pathophysiology of tinnitus").9-17
Because of the insidious nature of tinnitus and lack of standard measures of severity, true prevalence is difficult to calculate.18
CLINICAL EVALUATION
Tinnitus can be a presenting complaint or elicited during history-taking. Symptomatic patients should receive full evaluation, including a complete physical exam, medication history, and laboratory workup.
Adverse effect of drugs
Medications that commonly cause tinnitus symptoms are NSAIDs, chemotherapeutic agents, and antibiotics (eg, macrolides and fluoroquinolones). Amiodarone, ACE inhibitors, proton-pump inhibitors, and calcium-channel blockers have also been implicated. Paradoxically, anxiolytics and tricyclic antidepressants, which are sometimes used to treat tinnitus, have been linked to causing the condition.7
Laboratory tests and imaging
Testing should include investigation for infectious disease, autoimmune disorders, and vitamin deficiency.7 According to the American College of Radiology, imaging is unnecessary in the workup of primary tinnitus. Any suspicion of a vascular cause noted on the physical exam (eg, an associated bruit or venous hum), however, should be explored with imaging. Furthermore, any case of tinnitus that lateralizes also requires additional investigation. Modalities of choice are MRI, CT, and CT angiography.19
Continue to: Referral for audiology evaluation
Referral for audiology evaluation
When no underlying pathology can be identified for tinnitus, the patient should be sent for a full audiology evaluation to screen for associated hearing loss. Discussion of audiology screening tests is beyond the scope of this article; however, testing includes otoscopy, audiography, tympanography, otoacoustic emission testing, auditory brainstem-response testing, and vestibular evoked myogenic potential testing.7
Probing nonphysical impacts
Quality of life and overall emotional wellness, including cognitive function, should be investigated in patients with tinnitus. Two questionnaires commonly used in the assessment of tinnitus bother are the Tinnitus Handicap Inventory and the Tinnitus Reaction Questionnaire.7 In a large, systematic review, Trevis et al report that “64% of studies investigating depression found an increase in depressive symptoms in people with chronic tinnitus compared to hearing control groups, and 62% of studies investigating anxiety reported significantly increased anxiety symptoms.”5
MANAGEMENT
Tinnitus management should be viewed two ways: treatment of perceived loudness and treatment of comorbid symptoms relating to tinnitus bother.6 In the same meta-analysis, Trevis and colleagues found that patients with tinnitus had higher rates of anxiety, depression, and overall decline in cognitive function, including processing speed, concentration, and sleep disorders.5 It is useful to keep this observation in mind when reviewing treatment options for tinnitus.
Five classic pharmacotherapeutic approaches to tinnitus management are
- Anticonvulsants
- Antidepressants
- Anesthetics
- Anxiolytics
- Lidocaine.
Newer medications that show some promise are N-methyl-D-aspartate (NMDA) receptor antagonists, notably neramexane. Alternative pharmaceuticals include vitamin-based treatments, cannabinoids, and herbal compounds.
Continue to: The AAOS-HNS supports...
The AAO–HNS supports nonpharmacotherapeutic treatment of tinnitus; its guidelines include a recommendation for cognitive behavioral therapy (CBT) as primary therapy.6 In addition, tinnitus-retraining therapy, tinnitus-masking therapy/sound therapy, meditation/mindfulness, and yoga all have been studied for their ability to alleviate tinnitus bother.
Pharmacotherapeutic management
Anticonvulsants have failed to provide strong evidence of usefulness in the treatment of tinnitus and are not supported by the AAO–HNS as such.6 This conclusion notwithstanding, the anticonvulsants carbamazepine and gabapentin have historically been two of the more common medications used to treat tinnitus.
Carbamazepine is a glutamate receptor antagonist that suppresses seizure activity. Based on prior research suggesting that spontaneous firing within the auditory complex is similar to seizure activity, Iranian researchers explored the hypothesis that carbamazepine might lessen tinnitus severity. Their study revealed, however, that carbamazepine did not statistically significantly reduce the severity of tinnitus, compared to placebo.20 While carbamazepine may be of limited use in the treatment of subjective tinnitus, recent literature confirms that it is not only useful, but also diagnostic, in typewriter tinnitus (ie, having a staccato quality, like the sound of typewriter keys being depressed). Typewriter tinnitus is a secondary cause of tinnitus related to disruption of the stapes in the middle ear.21
Gabapentin works by promoting gamma-aminobutyric acid (GABA) production in the brain. GABA is an inhibitory neurotransmitter, thus slowing down signals between neurons. Following on preliminary research that detected low levels of GABA in the inferior colliculus of rodents with salicylate-induced tinnitus, Aazh and colleagues conducted a double-blind study of gabapentin—and concluded that it yielded no improvement in symptoms, compared to placebo.22
Valproic acid has not been formally investigated but is commonly incorporated in the treatment of tinnitus.23 Lamotrigine has provided similarly disappointing results in the treatment of tinnitus.24
Continue to: Antidepressants and anxiolytics
Antidepressants and anxiolytics. Based on the results of their early clinical trials, Sullivan and colleagues concluded that tricyclic antidepressants produced significant improvement in tinnitus symptoms, due to the analgesic effects of these drugs. The researchers studied nortriptyline specifically; in severely depressed patients, the drug reduced the loudness of tinnitus and depressive symptoms. In non-depressed subjects, however, nortriptyline was not as efficacious.25
Selective serotonin reuptake inhibitors have not had the same success as nortriptyline. In a study of paroxetine conducted by Oishi and colleagues, there was little evidence that the drug reduced the loudness of tinnitus, although overall, it did reduce tinnitus bother and anxiety.26
Included in the category of anxiolytics, benzodiazepines have long been used to treat severe tinnitus-induced anxiety, with some success. However, as Elgoyhen and Langguth point out, studies of benzodiazepines for tinnitus have been limited in size.23
The AAO–HNS does not support routine use of antidepressants and anxiolytics for tinnitus bother.7
NMDA receptor antagonists. In a recent clinical trial, neramexane was studied for its efficacy in tinnitus. Neramexane acts at the cholinergic nicotinic and NMDA receptors in the efferent auditory system. Its complex reaction is thought to prevent transmission of unwanted sound not only to structures within the auditory system but beyond, to the medial geniculate body and lateral nucleus of the amygdala. The trial has proved some benefit concerning overall perception of tinnitus loudness; a phase 2 trial is being conducted.27
Continue to: Intra-tympanic anesthetics
Intra-tympanic anesthetics. Anesthetics, such as lidocaine, have had limited success and results have not been found to be sustained.
Alternative medical managements
Traditional Chinese herbal medications have been used for centuries and are increasingly popular in Western culture. Hilton and colleagues studied Ginkgo biloba, or maidenhair tree, a traditional Chinese herbal supplement available as an extract and as dried leaves. The main action of the extract is vasoregulatory; antiplatelet effects are also seen. Adverse effects include gastrointestinal upset and headache. In a systematic review, Hilton and colleagues concluded that Ginkgo did not reduce overall tinnitus loudness or severity; the review was limited, however, by the fact that only two studies met criteria for inclusion.28
Vitamins, lipoflavinoids, zinc, manganese, and melatonin are all supplements marketed to improve tinnitus symptoms. However, a cross-sectional study confirmed prior research that did not show any benefit from the use of these supplements.29
Cannabinoids are being studied for their proposed antiepileptic effects. There is a popular misconception of Cannabis as a singular chemical when in fact, it is a plant that contains hundreds of chemicals that each act differently on the brain. In a review, Smith and Zheng30 explain that two cannabinoid receptors, CB1 and CB2, are represented, and exert their effects, in different areas of the brain. CB1 receptors block calcium influx in presynaptic terminals, resulting in an inhibitory effect on neurotransmitter release.
CB1 receptors have been found in the dorsal cochlear nuclei, prompting research interest in how cannabinoids affect neurotransmission of unwanted sounds of tinnitus. To date, however, there are conflicting data concerning the benefit of cannabinoids and tinnitus. In fact, Smith and Zheng state that some data suggest that cannabinoids might make tinnitus worse.30
Continue to: Nonpharmacotherapeutic management
Nonpharmacotherapeutic management
Cognitive behavioral therapy. Conceptualized by Aaron T. Beck in the 1960s, cognitive behavioral therapy (CBT) is the leading recommendation made by the AAO–HNS in its tinnitus treatment guidelines.6 Beck’s work centered on the idea that behaviors are modifiable thoughts, through analysis of past experiences and assumptions based on those experiences. By understanding the core belief that a patient attaches to a feeling, Beck hypothesized that behaviors or responses to those feelings could be changed; this is accomplished through discussion to dispel unwarranted fears and by teaching coping mechanisms, such as relaxation. The idea behind CBT in the management of tinnitus is clear: The sound cannot be eliminated, but the patient’s response to the sound can be modified. Ultimately, through this modified response or habituation, the patient can relax and live with the sound.31
Since anxiety, depression, and insomnia are common comorbidities of tinnitus, a psychologic approach remains in the forefront of treatment recommendations. Hoare and colleagues reported that in “a meta-analysis of 10 randomized trials evaluating different forms of CBT (by the therapist and over the Internet), CBT improved tinnitus symptoms compared to non-CBT controls.”7
Tinnitus retraining therapy (TRT) is another form of habituation therapy, introduced by Jastreboff in the 1990s. His work furthered the idea that tinnitus could be reframed, as it is in CBT. Simply, he proposed that systems outside the auditory complex—namely the autonomic nervous system and the limbic system—respond to the signal produced by damaged hair cells in the cochlear nuclei. TRT retrains connections to block or ignore these signals.13 Unlike CBT, the aim of TRT is to eliminate the perception of sound.
By educating patients about the physiologic mechanisms of tinnitus, TRT reduces patient anxiety related to the sound. The process of habituation follows counseling. To accomplish this, the patient wears a sound generator, similar in appearance to hearing aids, using broadband noise. The sound does not mask the tinnitus but closes the gap between silence and the perception of tinnitus. The sound generator is worn for six hours daily for approximately 12 months.
Multiple studies have employed Jastreboff’s original technique, including a clinical trial by Bauer and colleagues. The published outcome of this study confirmed that patients experienced a positive and lasting effect with TRT.32 In addition, a small study of TRT conducted by Barozzi and colleagues, using different colors of sound (ie, how the frequency of a given sound corresponds to the light-wave frequency of a particular color), found statistically significant improvement. Allowing patients to pick a sound that they found more pleasant increased the effectiveness of the treatment.33 (Patients can learn more about TRT by visiting www.tinnitus-pjj.com, hosted by tinnitus researcher Pawel J. Jastreboff.)
Continue to: Alternative nonmedical therapies...
Alternative nonmedical therapies have become popular; they include meditation, yoga, physical therapy, mindfulness, and tinnitus-masking treatment with sound.
Results of a study of yoga and meditation showed that patients felt more relaxed, but that these interventions had no effect on the severity of tinnitus. The principle behind yoga practice, according to Köksoy and colleagues, is that the discipline is thought to affect the limbic system by deactivating the sympathetic response to stimulation from surrounding sounds. In addition, Köksoy states, other researchers have provided evidence that yoga increases circulating levels of antioxidants, which in turn reduce oxidative stress.34
Particularly among members of the millennial generation, mindfulness has become a buzzword. The practice refers to a “method for facing, exploring, and alleviating suffering by relating to present experiences.”35 Roland and colleagues conducted a clinical trial of mindfulness practiced by a cohort of patients with bothersome tinnitus; results were based on scores gleaned from standard rating scales (eg, Global Bothersome Scale, Cognitive and Affective Mindfulness Scale-Revised, Cognitive Failures Questionnaire, Tinnitus Handicap Inventory, and Tinnitus Functional Index). Evaluated before and four weeks after cessation of therapy, subjects reported that tinnitus bother was reduced, but none showed statistically significant improvement in depression, anxiety, or cognitive ability.35
Used for more than 40 years, sound-based therapy has been discussed in conjunction with TRT.36 It is recognized as an approved but optional treatment by the AAO–HNS. In response to a 2010 study by Hobson that used sound-based therapy alone for tinnitus, Tunkel and colleagues cautioned that the modality showed little benefit. The major downside to acoustic therapy, according to the AAO–HNS clinical guidelines, is cost and patients’ excessive expectation of effectiveness.6
According to the AAO–HNS, repetitive-transcranial magnetic stimulation is not supported as a valid treatment for tinnitus because it can lead to seizures in patients who are taking medication that lowers the seizure threshold or who have a secondary cause of tinnitus, such as a tumor—therefore creating risk that outweighs any benefit.6
Continue to: CONCLUSION
CONCLUSION
For a large percentage of the population, chronic subjective tinnitus is a significant variable in the evaluation of quality of life. The condition is not completely understood and often displays features unique to the individual. Much of the initial response to research linking tinnitus with shared pathways typical for chronic pain, anxiety, and depression has resulted in pharmacotherapeutic management that is not always warranted—or successful.
Clinical research into the pathophysiology of tinnitus is providing a better understanding of the neurophysiologic mechanisms that underpin the science of chronic tinnitus. With this information, researchers can one day design medical management that targets specific receptors, resulting in greater management success.
The psychologic impact of tinnitus cannot be underestimated. When almost one-third of patients complain of debilitating symptoms that can also result in neurocognitive decline, tinnitus becomes a condition that cannot be ignored. Guidelines set forth by the AAO–HNS state that CBT and TRT offer some reprieve from symptoms and teach patients habituation without further damage to hearing. The use of broad-based sound generators has been well established as a useful management tool, although it is not curative.
The limitations of some studies that reviewed alternative medicines include small sample size and difficulty comparing research analysis because of disparities in tinnitus rating scales. Also, age bias, comorbid conditions, and study drop-out rates affected overall statistical significance of some studies. Additional, high-quality research is warranted in this area.
Continue to: Prevention of tinnitus...
Prevention of tinnitus through education on hearing loss and its causes should be regarded as implicit; occupational noise and recreational use of music devices put people at heightened risk for hearing loss and tinnitus. Information and open discussion that include the discovery of tinnitus symptoms during routine physical examination are recommended.
Last, providers who adhere to recognized guidelines will aid patients in coping with the challenges that tinnitus presents. As research continues to unravel the complex interaction between neurons, medical science is hopeful that curative treatments will become available.
1. Maltby MT. Ancient voices on tinnitus: the pathology and treatment of tinnitus in Celsus and the Hippocratic Corpus compared and contrasted. Int Tinnitus J. 2012;17(2):140-145.
2. Wolever RQ, Price R, Hazelton GA, et al. Complementary therapies for significant dysfunction from tinnitus: treatment review and potential for integrative medicine. Evid Based Complement Alternat Med. 2015;15:931418.
3. Shargorodsky J, Curhan GC, Farwell WR. Prevalence and characteristics of tinnitus among US adults. Am J Med. 2010;123(8):711-718.
4. Bhatt JM, Lin HW, Bhattacharyya N. Prevalence, severity, exposures, and treatment patterns of tinnitus in the United States. JAMA Otolaryngol Head Neck Surg. 2016;142(10):959-965.
5. Trevis KJ, McLachlan NM, Wilson SJ. A systematic review and meta-analysis of psychological functioning in chronic tinnitus. Clin Psychol Rev. 2018;60:62-86.
6. Tunkel DE, Bauer CA, Sun GH, et al. Clinical practice guideline: tinnitus. Otolaryngol Head Neck Surg. 2014;151(suppl 2):S1-S40.
7. Dinces EA. Treatment of tinnitus. UpToDate. April 12, 2018. www.uptodate.com/contents/treatment-of-tinnitus. Accessed September 17, 2018.
8. Gudwani S, Munjal SK, Panda NK, Kohli A. Association of chronic subjective tinnitus with neuro-cognitive performance. Int Tinnitus J. 2017;21:90-97.
9. Jastreboff PJ. 25 years of tinnitus retraining therapy. HNO. 2015;63:307-311.
10. Pujol R. Journey into the world of hearing. 2016. www.cochlea.eu/en. Accessed September 17, 2018.
11. Adjamian P, Hall DA, Palmer AR, et al. Neuroanatomical abnormalities in chronic tinnitus in the human brain.Neurosci Biobehav Rev. 2014;45:119-133.
12. Shore SE, Roberts LE, Langguth B. Maladaptive plasticity in tinnitus—triggers, mechanisms and treatment. Nat Rev Neurol. 2016;12(3):150-160.
13. Jastreboff PJ, Gray WC, Gold SL. Neurophysiological approach to tinnitus patients. Am J Otol. 1996;17(2):236-240.
14. Kaltenbach JA. Tinnitus: models and mechanisms. Hear Res. 2011;276:52-60.
15. Rauschecker JP, Leaver AM, Mühlau M. Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron. 2010;66(6):819-826.
16. Møller AR. Sensorineural tinnitus: its pathology and probable therapies. Int J Otolaryngol. 2016;2016:2830157.
17. Chen YC, Xia W, Chen H, et al. Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex. Hum Brain Mapp. 2017;38(5):2384-2397.
18. McCormack A, Edmonson-Jones M, Somerset S, Hall D. A systematic review of the reporting of tinnitus prevalence and severity. Hear Res. 2016;337:70-79.
19. Kessler MM, Moussa M, Bykowski J, et al; Expert Panel on Neurologic Imaging. ACR Appropriateness Criteria® Tinnitus. J Am Coll Radiol. 2017;14:S584-S591.
20. Gerami H, Saberi A, Nemati, S, et al. Effects of oxcarbazepine versus carbamazepine on tinnitus: a randomized double-blind placebo-controlled clinical trial. Iran J Neurol. 2012;11(3):106-110.
21. Sunwoo W, Jeon YJ, Bae YJ, et al. Typewriter tinnitus revisited: the typical symptoms and the initial response to carbamazepine are the most reliable diagnostic clues. Sci Rep. 2017;7:10615.
22. Aazh H, El Refaie A, Humphriss R. Gabapentin for tinnitus: a systematic review. Am J Audiol. 2011;20:151-158.
23. Elgoyhen AB, Langguth B. Pharmacological approaches to the treatment of tinnitus. Drug Discov Today. 2010;15:300-305.
24. Langguth B, Kreuzer PM, Kleinjung T, De Ridder D. Tinnitus: causes and clinical management. Lancet Neurol. 2013;12(9):920-930.
25. Sullivan M, Katon W, Russo J, et al. A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms. Arch Intern Med. 1993;153(19):2251-2259.
26. Oishi N, Kanzaki S, Shinden S, et al. Effects of selective serotonin reuptake inhibitor on treating tinnitus in patients stratified for presence of depression or anxiety. Audiol Neurootol. 2010;15(3):187-193.
27. Suckfüll M, Althaus M, Ellers-Lenz B, et al. A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus. BMC Ear Nose Throat Disord. 2011;11:1.
28. Hilton MP, Zimmermann EF, Hunt WT. Ginkgo biloba for tinnitus. Cochrane Database Syst Rev. 2013;CD003852. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003852.pub3/full. Accessed September 17, 2018.
29. Coelho C, Tyler R, Ji H, et al. Survey on the effectiveness of dietary supplements to treat tinnitus. Am J Audiol. 2016;25:184-205.
30. Smith PF, Zheng Y. Cannabinoids, cannabinoid receptors and tinnitus. Hear Res. 2015;332:210-216.
31. Martinez-Devesa P, Perera R, Theodoulou M, Waddell A. Cognitive behavioural therapy for tinnitus. Cochrane Database Syst Rev. 2010:CD005233. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD005233.pub3/full. Accessed September 17, 2018.
32. Bauer CA, Berry JL, Brozoski TJ. The effect of tinnitus retraining therapy on chronic tinnitus: a controlled trial. Laryngoscope Investig Otolaryngol. 2017;2(4):166-177.
33. Barozzi S, Ambrosetti U, Callaway SL, et al. Effects of tinnitus retraining therapy with different colours of sound. Int Tinnitus J. 2017;21:139-143.
34. Köksoy S, Eti CM, Karatas¸ M, Vayisoglu Y. The effects of yoga in patients suffering from subjective tinnitus. Int Arch Otorhinolaryngol. 2018;22(1):9-13.
35. Roland LT, Lenze EJ, Hardin FM, et al. Effects of mindfulness based stress reduction therapy on subjective bother and neural connectivity in chronic tinnitus. Otolaryngol Head Neck Surg. 2015;152(5):919-926.
36. Ibarra D, Tavira-Sanchez F, Recuero-Lopez M, Anthony BW. In-ear medical devices for acoustic therapies in tinnitus treatments, state of the art. Auris Nasus Larynx. 2018;45:6-12.
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13. Jastreboff PJ, Gray WC, Gold SL. Neurophysiological approach to tinnitus patients. Am J Otol. 1996;17(2):236-240.
14. Kaltenbach JA. Tinnitus: models and mechanisms. Hear Res. 2011;276:52-60.
15. Rauschecker JP, Leaver AM, Mühlau M. Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron. 2010;66(6):819-826.
16. Møller AR. Sensorineural tinnitus: its pathology and probable therapies. Int J Otolaryngol. 2016;2016:2830157.
17. Chen YC, Xia W, Chen H, et al. Tinnitus distress is linked to enhanced resting‐state functional connectivity from the limbic system to the auditory cortex. Hum Brain Mapp. 2017;38(5):2384-2397.
18. McCormack A, Edmonson-Jones M, Somerset S, Hall D. A systematic review of the reporting of tinnitus prevalence and severity. Hear Res. 2016;337:70-79.
19. Kessler MM, Moussa M, Bykowski J, et al; Expert Panel on Neurologic Imaging. ACR Appropriateness Criteria® Tinnitus. J Am Coll Radiol. 2017;14:S584-S591.
20. Gerami H, Saberi A, Nemati, S, et al. Effects of oxcarbazepine versus carbamazepine on tinnitus: a randomized double-blind placebo-controlled clinical trial. Iran J Neurol. 2012;11(3):106-110.
21. Sunwoo W, Jeon YJ, Bae YJ, et al. Typewriter tinnitus revisited: the typical symptoms and the initial response to carbamazepine are the most reliable diagnostic clues. Sci Rep. 2017;7:10615.
22. Aazh H, El Refaie A, Humphriss R. Gabapentin for tinnitus: a systematic review. Am J Audiol. 2011;20:151-158.
23. Elgoyhen AB, Langguth B. Pharmacological approaches to the treatment of tinnitus. Drug Discov Today. 2010;15:300-305.
24. Langguth B, Kreuzer PM, Kleinjung T, De Ridder D. Tinnitus: causes and clinical management. Lancet Neurol. 2013;12(9):920-930.
25. Sullivan M, Katon W, Russo J, et al. A randomized trial of nortriptyline for severe chronic tinnitus. Effects on depression, disability, and tinnitus symptoms. Arch Intern Med. 1993;153(19):2251-2259.
26. Oishi N, Kanzaki S, Shinden S, et al. Effects of selective serotonin reuptake inhibitor on treating tinnitus in patients stratified for presence of depression or anxiety. Audiol Neurootol. 2010;15(3):187-193.
27. Suckfüll M, Althaus M, Ellers-Lenz B, et al. A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus. BMC Ear Nose Throat Disord. 2011;11:1.
28. Hilton MP, Zimmermann EF, Hunt WT. Ginkgo biloba for tinnitus. Cochrane Database Syst Rev. 2013;CD003852. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003852.pub3/full. Accessed September 17, 2018.
29. Coelho C, Tyler R, Ji H, et al. Survey on the effectiveness of dietary supplements to treat tinnitus. Am J Audiol. 2016;25:184-205.
30. Smith PF, Zheng Y. Cannabinoids, cannabinoid receptors and tinnitus. Hear Res. 2015;332:210-216.
31. Martinez-Devesa P, Perera R, Theodoulou M, Waddell A. Cognitive behavioural therapy for tinnitus. Cochrane Database Syst Rev. 2010:CD005233. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD005233.pub3/full. Accessed September 17, 2018.
32. Bauer CA, Berry JL, Brozoski TJ. The effect of tinnitus retraining therapy on chronic tinnitus: a controlled trial. Laryngoscope Investig Otolaryngol. 2017;2(4):166-177.
33. Barozzi S, Ambrosetti U, Callaway SL, et al. Effects of tinnitus retraining therapy with different colours of sound. Int Tinnitus J. 2017;21:139-143.
34. Köksoy S, Eti CM, Karatas¸ M, Vayisoglu Y. The effects of yoga in patients suffering from subjective tinnitus. Int Arch Otorhinolaryngol. 2018;22(1):9-13.
35. Roland LT, Lenze EJ, Hardin FM, et al. Effects of mindfulness based stress reduction therapy on subjective bother and neural connectivity in chronic tinnitus. Otolaryngol Head Neck Surg. 2015;152(5):919-926.
36. Ibarra D, Tavira-Sanchez F, Recuero-Lopez M, Anthony BW. In-ear medical devices for acoustic therapies in tinnitus treatments, state of the art. Auris Nasus Larynx. 2018;45:6-12.
