Efficacy of donepezil in patients with chronic tinnitus

Tinnitus is any perception of sound that occurs in the absence of an external auditory stimulus. Donepezil, commonly prescribed for dementia, has not yet been evaluated in individuals with tinnitus. By increasing synaptic availability of acetylcholine, a neurotransmitter widely distributed in the central nervous system and potentially neuroprotective against glutamate induced excitotoxicity, donepezil may offer a pharmacological approach for the management of this condition.

We conducted a double-blind, prospective, randomized controlled trial with a sample of 35 each in a chronic subjective, non-somatosensory tinnitus group and an age- and gender-matched control group. Participants received either donepezil or a placebo for 3-months. Treatment effects were monitored using scales and questionnaires: THI, VAS, CDR, MMSE; and psychoacoustic measurements of tinnitus.

No statistically significant difference in symptom improvement was observed between the donepezil and placebo groups as assessed by the evaluation instruments. Notably, analysis of confidence intervals for patients achieving a minimum improvement of ≥ 7 and ≥ 11-points in THI scores suggested a potential clinically meaningful trend favoring donepezil. Additionally, complete remission of tinnitus was observed in a single patient, occurring only in the donepezil group.

In the present double-blind, randomized, placebo-controlled clinical trial, no statistically significant difference was identified between the groups regarding the primary outcome. However, the donepezil-treated group demonstrated better performance than the placebo group, and a possible indication of greater clinical benefit was observed in the treatment group in those using amplification, suggesting a potential therapeutic relevance, but larger, more in-depth studies are needed to confirm our findings.