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

Abstract

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.

Repetitive Transcranial Magnetic Stimulation for Tinnitus Treatment in Vestibular Schwannoma: A Pilot Study

“…Considering the hypothesized pathophysiology of TN driven by a central maladaptation, rTMS has been suggested in TN treatment several years ago. However, the results have been divergent and even contradictory (21,24,(26)(27)(28)(29). rTMS applies a train of repetitive magnetic pulses to alter the excitability of the neurons and modulate cortical activity.…”

“…However, the number of treated patients in this study is too low to draw final conclusions. Additionally, the sensitivity of the THI questionnaire might be-although widely used (21,36,37)-too low to detect slight rTMS-related TN improvements (52,53). In contrast, there was a clear effect of rTMS on the TMT values.…”

“…Having a central origin, TN is hardly accessible to therapy (20). In the last years, there is a growing interest in using repetitive transcranial magnetic stimulation (rTMS) in TN therapy (20)(21)(22)(23)(24). rTMS is suggested to modify the excitability of relevant neurons and neurotransmitter systems in TN (25).…”

“…rTMS is suggested to modify the excitability of relevant neurons and neurotransmitter systems in TN (25). However, the results have been divergent and even contradictory (21,24,(26)(27)(28)(29). First, there are still unsolved methodological issues, e.g., uncertainties concerning appropriate stimulation sites and stimulation intensities (20,23).…”

Heading for personalized rTMS in tinnitus: reliability of individualized stimulation protocols in behavioral and electrophysiological responses

“…Nevertheless, its clinical effectiveness is still not obvious. Recent reviews and meta-analyses conclude that there is no clear indication for an effect (Dong et al, 2020; Berthold Langguth, 2020; Zenner et al, 2017), while others report potential effectiveness for its clinical administration (Lefaucheur et al, 2014; Londero et al, 2018), especially over the auditory cortex (Lefebvre-Demers et al, 2020). This lack of evidence may be explained by the fact that there is still a certain ambiguity concerning the correct rTMS parameters (e.g., frequency or position) for the application in tinnitus.…”