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