Melatonin For Tinnitus Clinical Trial

Tinnitus, or persistent ear ringing, has no definitive treatment.  I had recently posted a summary of the status of this disorder based on a research review.

Since that post, a small but important placebo-controlled clinical trial examined the effect of melatonin on a group of subjects with tinnitus.

Here are the key elements of the study design from this clinical trial:
Subjects: Chronic tinnitus of at least 6 months duration as primary complaint (subjects ranged in age from 34 to 86)
Clinical Trial Design: 3 mg melatonin versus placebo for 30 days switchover to other assignment for an additional 30 days
Outcome Measure: Improvement defined as improvement in at least two tinnitus rating scales from 3 administered (Tinnitus Matching, Tinnitus Severity Index, Self-Rated Tinnitus)

In the analysis of the outcome of the trial, 57% of subjects were rated as improved during the melatonin phase while 25% were rated as improved during the placebo phase.   This was a statistically significant difference for the active drug.

Subjects who reported improvement with the melatonin trial were more likely to have the following clinical features:

• male gender
• bilateral tinnitus
• history of loud noise exposure
• no history of previous treatment for tinnitus
• no comorbid anxiety or depression
• higher Tinnitus Matching and Tinnitus Severity Index scores prior to the study

One of the problems with the design in this study is controlling for the potential confounding effect of improved sleep on tinnitus severity reporting.  Individuals who have improvement in sleep with melatonin may generally feel better and report improvement in a variety of domains.  An active non-melatonin comparator hypnotic, i.e. Ambien (zolpidem) would need to be included to determine if melatonin specifically contributes to reducing tinnitus.

The authors note potential mechanisms for melatonin in tinnitus include it's antioxidant effect, autonomic nervous system effects, effects on blood pressure or muscle tone. 

Larger multicenter studies confirming this study result are needed before a significant change in clinical practice can be recommended.  Since melatonin is a generic drug, such a study will likely need public research funding to be completed.

Molecular model of the compound melatonin from the Wikipedia Creative Commons authored by sbrools under the GNU Free Documentation License.

Hurtuk A, Dome C, Holloman CH, Wolfe K, Welling DB, Dodson EE, & Jacob A (2011). Melatonin: can it stop the ringing? The Annals of otology, rhinology, and laryngology, 120 (7), 433-40 PMID: 21859051

Advances in Treatment of Tinnitus (Ear Ringing)

Tinnitus is a common neurological condition affecting up to 10% or more of elderly individuals.  Variable it severity, in it's most serious form it can be disabling and quite distressful.  Due to the chronic nature of the disorder, many patients with tinnitus develop depression.  Suicide rates have been estimated to be increased in those with tinnitus-related. 

Althought the exact cause is unknown for tinnitus, abnormalities in spontaneous neural activity in the auditory brain system are a suspected mechanism.  Animal models of tinnitus support abnormal neuronal activity in the auditory system including: increased spontaneous activity (hyperactivity), increased neuronal burst activity and impairment in timing of neuronal discharges.

Significant research is targeted to new an innovative treatment strategies in the hope to reduce suffering for those with tinnitus.  Transcranial magnetic stimulations (TMS) is a potential treatment modality.  TMS has been shown to alter excitatory and inhibitory brain ciruits in the brain with the effects dependent on the region receiving the stimulus.  So it was reasonable to explore the potential role of TMS in tinnitus.

Dr. Jay Piccirillo and colleagues at the Washington University School of Medicine, recently published an early clinical trial of TMS in tinnitus.  Fourteen patients between 42 and 59 underwent a double-blind randomized crossover  trial.  Unfortunately, the trial proved to be negative with sham treatment producing the same effect as active TMS stimulation.

Although tolerated well, the TMS stimulation that was done daily for two weeks did not influence patients subject distress with their tinnitus.  The authors commented that some previous postitve reports of TMS in tinnitus were either uncontrolled or did not guard against  placebo effects.  Their study was well-controlled and casts doubt on some of the previous reports.   The authors did note it is possible their trial was not of sufficient duration to induce therapeutic changes.  They also noted their sample is somewhat unusual.  The required subjects to have high tinnitus severity rating but to not be depressed.  The screened over 285 subjects to get the 22 enrolled in the study.  Obviously, many of those with severe tinnitus were at least moderately depressed as they used a cutoff score of over 14 on the Beck Depression Inventory.

On a more hopeful note, an early online study published in the International Journal of Audiology examing tinnitus treatment found evidence of significant symptom reduction with two available treatments.  Tinnitus commonly occurs in conjuction with high frequency hearing loss.  This study randomized subjects to receive either an open ear digital hearing aid or us of an ear sound generator.  Both groups received education about tinnitus along the model known as Tinnitus Retraining Therapy.  Both groups had about a 50% reduction in the level of distress from their tinnitus.

So although there are not yet any revolutionary tinnitus treatment, research continues to find better approaches to this common.  In the mean time, open ear digital hearing aids and noise generators may provide significant reduction in distress for many individuals
 

Piccirillo JF, Garcia KS, Nicklaus J, Pierce K, Burton H, Vlassenko AG, Mintun M, Duddy D, Kallogjeri D, & Spitznagel EL Jr (2011). Low-frequency repetitive transcranial magnetic stimulation to the temporoparietal junction for tinnitus. Archives of otolaryngology--head & neck surgery, 137 (3), 221-8 PMID: 21422304

Parazzini M, Del Bo L, Jastreboff M, Tognola G, & Ravazzani P (2011). Open ear hearing aids in tinnitus therapy: An efficacy comparison with sound generators. International journal of audiology PMID: 21595527

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