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Hearing Journal:
doi: 10.1097/01.HJ.0000390820.25242.b4
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A guide to pharmacologic management of target symptoms of severe tinnitus

Centore, Linda S.

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Linda S. Centore, RN, PhD, is a Nurse Psychologist and Health Sciences Clinical Professor, and is the Chair, Division of Individual and Community Dentistry, Department of Preventive and Restorative Dentistry, University of California, San Francisco. Readers may contact Dr. Centore at Linda.Centore@ucsf.edu.

Patients who report severe tinnitus often describe a highly distressing experience leading to significant irritation, annoyance, insomnia, and difficulty coping. This can be highly intrusive and interfere with the ability to work, play, and enjoy life. When sufficiently severe, the distress may go beyond what the individual can tolerate and lead to a feeling of being overwhelmed. Medication is necessary when patients exhaust their emotional and physical reserves in coping with a noxious sensation.

Distressing symptoms of tinnitus include the perceived loudness itself, as well as insomnia, difficulty concentrating, anxiety, agitation, obsessive thinking about the tinnitus, worry about job performance, despair, depression, fear of sound, and hyperacusis.1,2 For each of the problem target symptoms, a thorough evaluation is needed. Where these symptoms go beyond the tinnitus management counseling, referral to primary care is warranted.

Insomnia is a common complaint with severe tinnitus and is associated with the risk of anxiety and depression.3–4 Understanding the nature and duration of the insomnia, etiology of awakenings, and degree of daytime function allows the primary-care clinician to design appropriate behavioral and pharmacologic interventions.5

Non-pharmacologic interventions for insomnia are preferred and should be attempted first. Good sleep hygiene involves keeping the same sleep/wake time and avoiding daytime naps and stimulating television or reading before bedtime. In addition, patients should limit caffeine intake for 8 hours before bedtime, limit alcohol intake for 4 hours before bedtime, and limit exercise for 3 hours before bedtime.

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ANTI-INSOMNIA MEDICATIONS

The choice of medication for insomnia depends on the type of insomnia and etiology. Paradoxically, some of the very medications associated with causing tinnitus may also help lessen it in some individuals. Classes of medication associated with tinnitus include analgesics, antibiotics, chemotherapeutic agents, cardiac, vascular, gastrointestinal, hypnotics, and antidepressants.6–7 In choosing a medication for a patient, the primary-care clinician should do a thorough medication history and take other systemic conditions and medication interaction effects into account.

Anti-insomnia agents include barbiturates, benzodiazepines (BDZ), non-benzodiazepines (NBDZ), and sedating antidepressants. Barbiturates are rarely used anymore due to their high potential for abuse and significant withdrawal symptoms.

When used safely, benzodiazepines (BDZ) are effective for the short-term management of sleep. They act by enhancing the action of a neurotransmitter GABA (y-Aminobutyric acid) that causes central nervous system depression and sedation. Examples of benzodiazepines used for sleep management include estazolam (ProSom), flurazepam (Dalmane), quazepam (Doral), temazepam (Restoril), and triazolam (Halcion).

Their advantages are that they promote sleep and can be used up to 4 months as needed. Their disadvantages are that may lead to daytime drowsiness or hangover and to psychological and physiological dependence and they require a gradual taper to discontinue. Signs of benzodiazepine abuse include ongoing requests for dose escalation, impaired function, overuse, and requests for new prescriptions early. In addition, withdrawal symptoms from benzodiazepines include nausea, vomiting, muscle cramps, sweating, shaking/tremors, and seizures.8

Chronic maintenance on a benzodiazepine for sleep may work fine. However, BDZ may be a short-term solution to a long-term problem. If dose escalation occurs, it merits a re-evaluation of the sleep problem in the context of a co-morbid mental health condition. In a study of 113 patients receiving discontinuation treatment for long-term benzodiazepine use (>3 months), 75% were maintained on a low dose, 50% reported continued therapeutic effectiveness on the same dose without escalation, and many shifted from a prescribed dosing to “as needed” without increasing the dose.9

In clinical practice, patients with severe tinnitus and without a history of substance abuse appear to use the benzodiazepine sparingly when the tinnitus is most severe. However, caution needs to be exercised with patients who have a substance abuse history who are at increased risk for abuse of benzodiazepines. These individuals may derive greater benefit from a different class of medications—sedating antidepressants.

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Benzodiazepines and tinnitus

Benzodiazepines, as both anti-insomnia and anti-anxiety agents, have been studied for tinnitus. The best study on benzodiazepines was a small (n=40), prospective, placebo-controlled, double-blind study on Tinnitus Registry patients with constant tinnitus of at least 1 year's duration. The study examined the daily use of alprazolam for 58 days. By weeks 4 and 12, at a maximum of 1.5 mg of alprazolam, 76% of the treatment group reported a reduction in loudness measures on objective (tinnitus synthesizer for pitch matching, loudness matching, minimum masking levels, and residual inhibition) and subjective VAS measures, compared to 5% of the placebo group.10 However, a small, double-blind, triple crossover study (n=21) involving diazepam did not show a reduction in tinnitus volume.11

Severe tinnitus may cause anxiety or agitation that interferes with concentration, mood, and daytime function. Cognitive awareness or hyperawareness of the tinnitus may lead to monitoring, which in turn can lead to catastrophic misinterpretation and the belief that tinnitus may become progressively louder.12 This distorted cognitive appraisal may increase tinnitus-associated anxiety or agitation. Benzodiazepines are used for the short-term treatment of acute anxiety, PTSD, generalized anxiety, and panic attacks.13

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Non-benzodiazepines

While results on benzodiazepines are mixed, empirical use of benzodiazepines reveals that some patients experience benefit with a reduction in loudness and/or annoyance when taken in low divided doses “as needed” across the day. Non-benzodiazepines (NBDZ) are currently more commonly used for insomnia because they have a shorter duration and are less likely to cause a “hangover.” NBDZ have a non-selective action on GABA, an inhibitory neurotransmitter, but, unlike BDZ, they do not provide smooth muscle relaxation or increase the seizure threshold.8

Clinically addressing insomnia in patients with severe tinnitus improves ability to function and tolerate the noxious tinnitus sensation. Advantages of NBDZ include that they are non-addictive and there is no shortening of REM or stage 4 sleep, as with BDZ. Disadvantages are that NBDZ are shorter acting and have been criticized for not providing a sufficient number of hours of sleep due to their shorter action. This has led to controlled-release or extended-release versions. Since these medications affect benzodiazepine receptors, they may present some potential for abuse and should be used with caution.

Some patients with severe tinnitus benefit from a NBDZ such that this may be considered helpful for insomnia. The importance of a good night's sleep for people with severe tinnitus cannot be overstated. Just as poor sleep aggravates chronic pain, it also heightens the perception of tinnitus. Restorative sleep often leads to feeling more resilient and better able to cope. Examples of NBDZ are zolpidem (Ambien), eszopiclone (Lunesta), zaleplon (Sonata), and ramelteon (Rozerem).

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ANTIDEPRESSANTS

Antidepressant medications were discovered serendipitously with the monoamineoxidase inhibitors (MAOIs- Nardil), and came into use by the 1950s. The tricyclics (TCAs- Elavil) appeared in the 1960s, and the selective serotonin reuptake inhibitors (SSRIs-Prozac) by the late 1980s.14

Norepinephrine, serotonin, and dopamine are all thought to play a role in the pathogenesis of depression. Currently, there are several classes of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), norepinephrine/dopamine reuptake inhibitors (NDRIs), tricyclic antidepressants (TCAs), alpha2 noradrenergic antagonists, serotonin 2 agonists/blockers/serotonin reuptake inhibitors (SARIs/SSRIs), and monoamine oxidase inhibitors (MAOIs).

All antidepressants are considered equally efficacious in that no particular one has shown better than 50%–70% effectiveness with depression.15–16 Antidepressant medications provide a “ceiling” for anxiety and a “floor,” regulating mood and increasing resilience. Non-pharmacologic treatment is provided first and may include structured time, exercise, 10,000-Lux light therapy, and psychological counseling. Severe depression, with its risk of suicide, usually requires medication.

Antidepressants have been studied in the treatment of tinnitus with mixed results. A 12-week, double-blind, randomized, placebo-controlled trial (n=92) of patients with severe tinnitus and depression who were treated with nortriptyline (Pamelor) showed a significant decrease in depression, MPI tinnitus interference, and tinnitus loudness.17 A 16-week, double-blind, randomized, placebo-controlled trial (n=76) of patients who were treated with sertraline (Zoloft) also showed a decrease in anxiety, depression, TSQ score, and perceived loudness.18

These studies appear to indicate that for patients with anxiety or depressive symptoms accompanying tinnitus, an antidepressant may help both affective symptoms and tinnitus interference and/or perceived loudness. However, a 31-day, double-blind, randomized, placebo-controlled trial (n=120) of non-depressed patients with severe tinnitus treated with paroxetine (Paxil) showed no differences on anxiety or depression measures, the THQ, or tinnitus loudness.19 The only significant finding in that 2005 study was a post-hoc question posed by the audiologist in which subjects acknowledged a significant decrease in aggravation caused by tinnitus.

There is mounting suspicion that tinnitus involves a strong central component with auditory cortical plasticity resulting in changes in the auditory cortex and limbic system.20 Serotonin 5-HT is ubiquitous and plays an important role in altering sensory pathways, modifying emotion, and regulating the sleep/wake cycle.21 It may be that antidepressants address only the cognitive and emotional appraisal of the tinnitus on a continuum from annoyance to aggravation. Antidepressants may provide a small benefit for patients with severe tinnitus with or without significant anxiety or depression if only to reduce the bothersome quality of severe tinnitus.

Table 1 contains a summary of the medications discussed in this article.

Table 1
Table 1
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CONCLUSIONS

Persistent, severe tinnitus should be managed by a multidisciplinary team. Patients experiencing severe tinnitus deserve the compassion and attention of their audiologist and primary-care clinician along with other specialists as needed. The uncertainty attached to having severe tinnitus along with the etiologic ambiguity is highly stressful.

The primary-care clinician should manage the patient's chronic tinnitus just as he or she does other common conditions. Audiology and otolaryngology are in a unique position to provide education to primary-care providers who may not be well-informed about tinnitus etiology and management. With our aging population, tinnitus will likely become an even more significant problem than it is now.

Habituation to the distorted tinnitus perception is possible with the wide range of tools available to audiology. Benzodiazepines and antidepressants may address co-morbid target symptoms such as insomnia, anxiety, and depression that negatively affect tinnitus perception and lessen coping.

The well-being of patients with severe tinnitus depends on seamless communication between the audiologist and the primary-care clinician. It is of utmost importance to replace a delayed and disjointed healthcare response with one that effectively diminishes tinnitus suffering and softens the impact of a chronic condition affecting millions.

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REFERENCES

1. Erlandsson SI: Psychological profiles of tinnitus patients. In Tyler RS, Tinnitus. San Diego: Singular Thomas Learning Publishing, 2000: 25–57.

2. Holmes S, Padgham ND: Review paper: More than ringing in the ears: A review of tinnitus and its psychosocial impact. J Clin Nursing 2009;18:2927–2937.

3. Tyler RS, Baker LJ: Difficulties experienced by tinnitus sufferers. J Sp Hear Dis 1983;48:150–154.

4. Folmer RL: Long-term reductions in tinnitus severity. BMC Ear Nose Throat Dis 2002;2(3):1–9.

5. Elliott AC: Primary care assessment and management of sleep disorders. J Am Acad Nurse Pract 2001;13(9):409–417.

6. Crummer RW, Ghinwa AH: Diagnostic approach to tinnitus. Am Fam Physic 2004;69(1):120–126.

7. Lee CA, Mistry D, Uppal S, Coatesworth AP: Otologic side effects of drugs. J Laryngol Otol 2005;119:267–271.

8. Edmunds MW, Mayhew MS: Pharmacology for the Primary Care Provider. St. Louis: Mosby, 2009.

9. Romach M, Busto U, Somer G, et al.: Clinical aspects of chronic use of alprazolam and lorazepam. Am J Psychiatr 1995;152:1161–1167.

10. Johnson RM, Brummett R, Schleuning A: Use of alprazolam for relief of tinnitus. Arch Otolaryngol Head Neck Surg 1993;119:842–845.

11. Kay NJ: Oral chemotherapy in tinnitus. Brit J Audiol 1981;15:123–124.

12. Sweetow RW: Cognitive-behavior modification. In Tyler RS, Tinnitus. San Diego: Singular Thomas Learning Publishing, 2000: 287–311.

13. Agency for Healthcare Research & Quality (AHRQ): Practice guideline for the treatment of patients with acute stress disorder. Nat Guideline Clearinghouse. 2004. Retrieved from www.guideline.gov/content.aspx?id=5954&search=medication+treatment+of+anxiety.

14. Lieberman JA: History of the use of antidepressants in primary care. Primary Care Companion J Clin Psychiatr 2003;5(Supplement 7):6–10.

15. Schatzberg AF, Cole JO, DeBattista C: Manual of Clinical Psychopharmacology, 6th ed.. Washington DC: American Psychiatric Publishing, 2007.

16. Agency for Healthcare Research & Quality (AHRQ): Comparative effectiveness of second generation antidepressants in the pharmacologic treatment of adult depression. Executive summary. January 2007: No. 07-EHC007-1.

17. Sullivan M, Katon W, Russo J, et al.: A randomized trial of nortriptyline for severe chronic tinnitus. Arch Internal Med 1993;153:2252–2259.

18. Zoger S, Svedlund J, Holgers KM: The effects of sertraline on severe tinnitus suffering: A randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2006;26(1):32–39.

19. Robinson SK, Viirre ES, Bailey KA, et al.: Randomized placebo-controlled trial of a selective serotonin reuptake inhibitor in the treatment of nondepressed tinnitus subjects. Psychosomatic Med 2005;67:981–988.

20. Eggermont JJ, Roberts LE: The neuroscience of tinnitus. Trends Neurosci 2004;27(11):676–682.

21. Simpson JJ, Davies WE: A review of evidence in support of a role for 5-HT in the perception of tinnitus. Hear Res 2000;145:1–7.

© 2010 Lippincott Williams & Wilkins, Inc.

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