Background/Objectives: An exploratory study was conducted to investigate the effect of Ginkgo biloba extract EGb 761^® in the management of chronic tinnitus, and whether comorbidities have an impact on the treatment outcome. Methods: The exploratory, uncontrolled, open-label study enrolled 170 patients (Full Analysis Set) with chronic tinnitus who took 120 mg EGb 761^® twice daily for 24 weeks. Outcomes were assessed using the Tinnitus Questionnaire, Tinnitus Handicap Inventory, and 11-Point Box Scales for loudness and annoyance. Comorbidities were recorded with audiometry, the Hospital Anxiety and Depression Scale, and the Perceived Stress Questionnaire. The effectiveness was further examined in responder analyses (at least 30% score reduction in 3 out of 4 outcomes) and in subgroups defined by baseline anxiety, hearing impairment, stress and depression. Results: At week 24, significant improvements were observed in all tinnitus-related outcomes compared to baseline (all p < 0.0001). In subgroup analyses, patients with high baseline anxiety or stress as well as those with normacusis improved more, whereas baseline depression had no influence. The overall response rate was 18.8%. Conclusions: The results of this exploratory study indicate that EGb 761^® improved complaints in patients with chronic tinnitus. The therapy appears to be particularly beneficial for patients with normal hearing and/or concomitant anxiety and/or stress. Trial registration: The study was registered at ISRCTN (ISRCTN83863387, registration date 14 October 2016).

The present exploratory, uncontrolled, open-label study investigated the effect of Ginkgo biloba extract EGb 761® in the management of chronic tinnitus, and whether comorbidities have an impact on the treatment outcome. The full analysis set comprised 170 patients with chronic tinnitus who took 120 mg EGb 761® twice daily for 24 weeks. Outcomes were assessed using the Tinnitus Questionnaire, Tinnitus Handicap Inventory, and 11-Point Box Scales for loudness and annoyance. Comorbidities were recorded with audiometry, the Hospital Anxiety and Depression Scale, and the Perceived Stress Questionnaire. The effectiveness was further examined in responder analyses (at least 30% score reduction in 3 out of 4 outcomes) and in subgroups defined by baseline anxiety, hearing impairment, stress and depression. At week 24, significant improvements were observed in all tinnitus-related outcomes compared to baseline (all p<0.0001). In subgroup analyses, patients with high baseline anxiety or stress as well as those with normacusis improved more whereas baseline depression had no influence. The overall response rate was 18.8%. The results of this exploratory study indicate that EGb 761® improved complaints in patients with chronic tinnitus. The therapy appears to be particularly beneficial for patients with normal hearing and/or concomitant anxiety and/or stress. Trial registration: The study was registered at ISRCTN (ISRCTN83863387, registration date October 14, 2016).

Introduction: Ginkgo extract EGb 761 demonstrated favourable therapeutic effects in peripheral and central vestibular syndromes. This pragmatic study explored whether administration of EGb 761 in patients with vertigo and dizziness of various aetiologies results in improvement of symptom intensity, posture, gait and ocular motor function, and whether specific patient subgroups benefit most from this treatment. Methods: This pragmatic open-label, multicentre clinical trial involved 179 patients with various vertigo and dizziness syndromes taking 240 mg of EGb 761 daily for 12 weeks. Patient-reported outcomes were assessed at 6 and 12 weeks using the Dizziness Handicap Inventory (DHI), the short form of the Vertigo Symptom Scale (VSS-SF) and a 11-point box scale to measure vertigo severity. A moderate treatment response was defined as an improvement of at least 30% from the baseline score. The Romberg test and Unterberger stepping test were carried out to clinically grade posture and gait instability. Spontaneous nystagmus detection was performed with and without fixation suppression. Subgroups were analysed using analysis of covariance models to explore potential effect modifiers. Results: A total of 174 patients (mean age: 52.2 years; 77.6% female) were enrolled. Compared to baseline, mean scores on the DHI, the VSS-SF and the 11-point box scale for vertigo severity showed statistically significant improvement (p < 0.0001) both after 6 and 12 weeks. After 12 weeks, two-thirds of patients (between 60.9% and 66.7%) showed a clinically relevant improvement in these patient-reported outcomes. The proportion of patients with a normal postural control in the Romberg test increased from 48.3% at baseline to 85.2% after 12 weeks. Meanwhile, the proportion of patients with abnormal results in the Unterberger stepping test decreased from 33.5% at baseline to 10.1% at week 12. Patients with episodic vertigo/dizziness, and those whose symptoms had lasted up to 6 months, improved more than those with continuous vertigo/dizziness and symptoms lasting more than 6 months. Conclusion: After 12 weeks, patient-reported and functional outcomes had significantly improved in patients with vertigo/dizziness. However, within the setting of this pragmatic study, it is not possible to discriminate between the effects of treatment, self-healing, or the natural course of the disease. Clinical Trial Registration: https://eudract.ema.europa.eu/ , identifier EUdraCT 2016-000316-15.

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.