Reduction of Tinnitus Severity by the Centrally Acting Muscle Relaxant Cyclobenzaprine: An Open-Label Pilot Study

Abstract

Tinnitus, the phantom perception of sounds, is a highly prevalent disorder. Although a wide variety of drugs have been investigated off label for the treatment of tinnitus, there is no approved pharmacotherapy. We report an open-label exploratory pilot study to assess the effect of muscle relaxants acting on the central nervous system on tinnitus patients. Cyclobenzaprine at high (30 mg) and low doses (10 mg), orphenadrine (100 mg), tizanidine (24 mg) and eperisone (50 mg) were administered to a maximum of 20 patients per group over a 12-week period. High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample. On the other hand, other treatments were not effective. These results were confirmed in an explorative analysis where baseline corrected THI and Clinical Global Impression scores at week 12 were compared between groups. The present open trial presents a new promising pharmacotherapy for tinnitus that should be validated in placebo-controlled double-blind trials.

The influence of psychological factors on tinnitus severity

“…Such site effect have been described earlier [32,34] and should always be considered both in multicenter studies and in the comparison of studies from different centers. The site effect is most probably due to a selection effect, which results in specific patient populations at different sites.…”

Partial to Complete Suppression of Unilateral Noise-Induced Tinnitus in Rats after Cyclobenzaprine Treatment

“…The hypothesis that cyclobenzaprine would reduce noise-induced tinnitus was based on evidence from early clinical reports regarding the potential efficacy of this compound on persistent tinnitus. In two recent open-label studies, cyclobenzaprine significantly reduced tinnitus distress and tinnitus handicap (Coelho et al 2012;Vanneste et al 2012). More importantly, however, is that in one of the studies, 24 % of cyclobenzaprine treated participants, who responded to treatment, showed a 53 % reduction in tinnitus loudness (Vanneste et al 2012).…”

“…Cyclobenzaprine, a tricyclic antidepressant analog (Lofland et al 2001;Van Hoey 2005) and muscle relaxant (Basmajian 1978;Katz and Dube 1988) has been suggested as effective in reducing tinnitus in clinical reports (Coelho et al 2012;Vanneste et al 2012). Although widely used commercially as a muscle relaxant, cyclobenzaprine's complex pharmacological actions on other functions are not well understood.…”

Linking the Tinnitus Questionnaire and the subjective Clinical Global Impression: Which differences are clinically important?

“…Accordingly, several recent clinical trials used a patient-rated CGI change as outcome criterium [32,33]. Therefore, patient-rated CGI scales represent a valid example of a reference anchor [26,34,35].…”