Effect of the vagus nerve stimulation combined with sound therapy for tinnitus treatment: a systematic review and meta-analysis.

BACKGROUND

Tinnitus is a prevalent hearing problem linked to anxiety and depression. It currently has no cure. This systematic review and meta-analysis aimed to explore the potential association of combining vagus nerve stimulation (VNS) with auditory stimulation in alleviating tinnitus, recognizing the exploratory nature of evidence.

METHODS

Six databases were searched from 1990 to 2023 (2025 updated) for randomized clinical trials, observational studies, and case studies with at least one group receiving invasive or non-invasive VNS with sound for tinnitus management. Eligible studies used validated questionnaires to quantify tinnitus distress or severity in patients compared with controls or pre-treatment status. Two reviewers extracted participant, intervention, blinding, assessment, and outcome data. The risk of bias was assessed with ROBINS-I for non-randomized studies and ROB2 for randomized controlled trials. PRISMA guidelines were followed.

RESULTS

Eight studies were included in the systematic review and six in the meta-analysis. The Tinnitus Handicap Inventory (THI) and the Visual Analogue Scale (VAS) were suitable for meta-analysis. The analysis was primarily based on within-group pre‑post changes, not between‑group comparisons. For THI, the standardized mean difference (SMD) was 0.53 (95% CI: 0.12-0.94, p = 0.01), while the weighted mean difference (WMD) was 12.52 (95% CI: 4.56-20.48, p < 0.001), surpassing 7 minimal clinically important difference (MCID) threshold. For VAS, SMD was 0.55 (95% CI: 0.14-0.96, p = 0.01), but WMD was 11.21 (95% CI: 4.79-17.63, p < 0.001) and the improvement fell short of the 15 MCID.

CONCLUSIONS

Within the limitations of an exploratory within‑group meta‑analysis, statistically and clinically significant reductions in THI were observed when VNS plus sound therapy. However, improvement in VAS was not clinically significant. These exploratory findings suggest a possible synergistic effect, but should not be considered conclusive evidence of comparative efficacy. Further controlled studies are needed.