Background: Comorbid occurrence of tinnitus and emotional symptoms of anxiety and depression is highly prevalent. The Ginkgo biloba extract EGb 761^® has been shown to be effective in reducing neuropsychiatric symptoms in patients with dementia and tinnitus. Methods: We performed a mediation analysis to evaluate direct effects of EGb 761^® on tinnitus severity, as well as indirect effects mediated by symptoms of depression and anxiety and by changed cognition. We pooled data from subsets of patients suffering from tinnitus that were enrolled in three double-blind, randomized, placebo-controlled clinical trials, which investigated the efficacy of EGb 761^® (240 mg/day for 22–24 weeks) in dementia with concomitant neuropsychiatric symptoms. Results: In total, 594 patients suffered from tinnitus (EGb 761^®, 289; placebo, 305). Direct effects of EGb 761^® on tinnitus severity (p < 0.001) in patients with mild to moderate dementia were found to represent about 60% of the total effect, whereas the indirect effects (p < 0.001) mediated by improvement of anxiety, depression and cognition represented about 40% of the total effect. Conclusions: EGb 761^® could be considered as a supporting treatment for tinnitus in elderly patients suffering from dementia, with added benefit in those with symptoms of depression or anxiety.

Background/Objectives: Tinnitus often occurs alongside the emotional symptoms of anxiety and depression. The Ginkgo biloba extract EGb 761^® was shown to be effective in reducing neuropsychiatric symptoms in elderly patients with both dementia and tinnitus, exerting direct effects on tinnitus severity and indirect effects mediated by improvement of anxiety, depression, and cognition. Whether the extent of the effects is influenced by the patient’s sex has not yet been investigated. We performed a conditional process analysis to evaluate this question. Methods: We analyzed the moderating role of sex on the direct and indirect effects of EGb 761^® on tinnitus severity using a first- and second-stage conditional process model. Results: Indirect effects of EGb 761^® on tinnitus severity mediated by improved cognition, anxiety, and depression did not differ between women and men (p > 0.05; all 95% bootstrap confidence intervals overlapped with zero). Moreover, direct treatment effects of EGb 761^® on tinnitus severity were statistically significant for both sexes (women, p < 0.0001; men, p = 0.0279). Conclusions: Beneficial effects of Ginkgo biloba extract EGb 761^® in dementia patients with tinnitus are likely to be unaffected by the patient’s sex. Further research into the influence of patient characteristics on the outcome of tinnitus drug treatment is encouraged.