Low-Frequency Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Tinnitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Chronic tinnitus affects approximately 10-15% of the population. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a promising and well-tolerated therapeutic strategy for chronic tinnitus. However, a recent large-scale multicenter clinical trial showed a negative result. Objective. This systematic review is aimed at assessing the efficacy and safety of low-frequency rTMS in chronic tinnitus. Methods. We searched PubMed, Embase, and Cochrane Library for randomized controlled studies of rTMS treatment of chronic tinnitus. A pooled analysis of standardized mean difference (SMD) was performed with 95% confidence intervals (CI). Results. Ten RCTs involving 567 participants were included in this review. Compared with sham stimulation, rTMS showed no significant efficacy in tinnitus severity and disability measured by Tinnitus Handicap Inventory (THI) in short-term (SMD=-0.04, 95% CI -0.23 to 0.16, P=0.72), medium-term (SMD=-0.13, 95% CI -0.43 to 0.17, P=0.41), and long-term (SMD=-0.16, 95% CI -0.38 to 0.05, P=0.14) follow-up. Tinnitus severity and disability measured by Tinnitus Questionnaire (TQ) also showed no significant improvement in short-term (SMD=-0.11, 95% CI -0.31 to 0.10, P=0.30), medium-term (SMD=-0.10, 95% CI -0.37 to 0.16, P=0.44), and long-term (SMD=-0.20, 95% CI -0.40 to 0.01, P=0.06) follow-up. Additionally, no statistically significant difference was shown in the changes of tinnitus loudness assessed by a visual analogue scale (VAS) between rTMS and sham groups in the short-term (SMD=-0.28, 95% CI -0.59 to 0.02, P=0.07), medium-term (SMD=-0.26, 95% CI -0.59 to 0.07, P=0.13), and long-term (SMD=-0.20, 95% CI -0.53 to 0.13, P=0.24) follow-up. Few mild or moderate adverse events were observed in both the rTMS and sham groups. Conclusion. Low-frequency rTMS is well tolerated but not effective in treating chronic tinnitus based on the current analysis of pooled data. Further studies with modified and uniform protocols are required to investigate the potential benefit of rTMS in chronic tinnitus.