Supervisors info:
Πέτρος Βλασταράκος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Παύλος Μαραγκουδάκης, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αλέξανδρος Δελίδης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Introduction: The prevalence of patients suffering from subjective chronic tinnitus is 10-15% worldwide and increases exponentially with age. The progress in neurosciences within the last fifteen years has led to better understanding of the pathophysiological mechanisms responsible for the occurrence of tinnitus. Among the available treatment modalities, none has demonstrated a real effect. Even cognitive behavioral therapy, which is the only one with positive value in dealing the psychological disorders associated with tinnitus, has little contribution in reducing its intensity. Recently, neuromodulation techniques have begun to gain ground over classical treatments in various neuropsychiatric fields, demonstrating significant benefit. Taking the aforementioned into account, the aim of the present study was to report on neuromodulation techniques primarily regarding their short-term effectiveness in reducing tinnitus severity and loudness, but also pertaining to their long-term effectiveness and safety.
Methods: A systematic review was conducted in EMBASE and Pubmed databases, including randomized controlled trials published in English from 2015 to September 2024. The review compared adults with chronic tinnitus receiving active neuromodulation treatment modalities, or different protocols of these treatments, to their counterparts receiving sham, placebo or acoustic treatment. The patients did not simultaneously receive any other type of therapy for tinnitus and their results were measured with either of the following standardized questionnaires: a) Tinnitus Handicap Inventory, b) Tinnitus Functional Index, or c) Tinnitus Questionnaire. The risk of bias was also assessed and where appropriate (three or above studies with similar protocol of the same technique), meta-analyses were performed.
Results: Twenty-six randomized controlled trials employing five different neuromodulation techniques were included in the study, with a total of 1576 tinnitus patients. Meta-analysis of pre- and post-treatment efficacy of eight transcranial direct current stimulation (tDCS) studies revealed a standardized mean difference (SMD) final outcome of -0,36 (95% CIs -0,75 to +0.02), while modified meta-analyses were performed in subgroups of the same technique, by target area. The corresponding meta-analysis result including five studies of repetitive transcranial magnetic stimulation (rTMS) was -0.15 (95% CIs -0,37 to +0,07). In terms of safety, only one serious adverse event related to permanent vocal cord paralysis in a vagus nerve stimulation study was reported across all studies.
Discussion: With the increasing recent interest for neuromodulation treatment in tinnitus, the present study sought to extract the best therapy protocol with synchronous elimination of factors causing high heterogeneity between studies. Taking the confirmed safety and promising effectiveness of these techniques into account, as well as the fact that they can be easily replicated, future research should focus on the right parameterization, aiming at finding a holistic treatment for tinnitus. Bimodal stimulation appears promising in this respect.
Conclusions: Neuromodulation was found to be sufficiently safe, especially regarding non-invasive techniques with minimal transient adverse events reported. The meta-analysis for post treatment effect of tDCS compared with placebo/sham treatment, showed significant improvement in reducing tinnitus severity, approaching borderline statistical significance (p=0,05); the corresponding outcome for rTMS was non statistically significant. Nevertheless, rTMS showed better long-term effect in some studies compared to the immediately post-treatment. Finally, bimodal stimulation shows highly promising positive results both in the short- and long-term. However, these data need to be further confirmed in randomized placebo-controlled studies in the future.
Keywords:
Tinnitus, Neuromodulation, tDCS, tRNS, rTMS, Acoustic CR, VNS, Bimodal stimulation
