Although transcranial direct current stimulation (tDCS) has already been used to manage tinnitus patients, paucity of reports and variations in protocols preclude a comprehensive understanding. Hence, we conducted a meta-analysis based on systemic review to assess effectiveness of tDCS in tinnitus management and to compare stimulation parameters. PubMed was searched for tDCS studies in tinnitus. For randomized controlled trials (RCTs), a meta-analysis was performed. A total of 17 studies were identified and 6 of them were included in the systemic review and 2 RCTs were included in the meta-analysis. Overall 39.5% responded to active tDCS with a mean tinnitus intensity reduction of 13.5%. Additionally, left temporal area (LTA) and bifrontal tDCS indicated comparable results. Active tDCS was found to be more effective than sham tDCS for tinnitus intensity reduction (Hedges'
Subjective tinnitus, a phantom sound perception in the absence of an identifiable objective, external sound source [
Although numerous management disciplines including pharmacological and nonpharmacological treatments have been introduced, evidence for a uniformly successful treatment that can eliminate tinnitus is lacking [
With the development of the idea that the unified tinnitus percept is an emergent network property resulting from activity in multiple, parallel, partially overlapping but separable networks [
Over the last decade, noninvasive neuromodulations such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcutaneous electrical nerve stimulation, and neurofeedback have been used, as well as invasive neuromodulation techniques. These include implantable cortical electrodes on the auditory and the dorsolateral prefrontal cortex (DLPFC), as well as subcutaneous occipital nerve stimulation, and deep brain stimulation [
Of these neuromodulation methods, tDCS might become a clinically useful noninvasive neuromodulation technique for tinnitus suppression due to its low cost, easy, painless application, and its longer residual inhibition than TMS. tDCS delivers low direct currents (0.5–2 mA) via scalp electrodes to the cerebral cortex that result in the modulation of cortical excitability for variable periods outlasting the stimulation period [
tDCS has been applied for treating major depression [
To identify all studies available, PubMed searches on tDCS studies on tinnitus according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines [
All identified studies were examined by 2 authors (J. J. Song and S. Vanneste) independently. The inclusion criteria for the current meta-analysis were that studies (1) published in a peer-reviewed journal, (2) reporting on tDCS in the management of tinnitus patients, (3) dealing with original data of open-label or RCT with tinnitus loudness as the outcome measure, (4) performed by randomized parallel or crossover design, with sham control, and (5) where both participants and raters had to be unaware of treatment condition. Percentage change in tinnitus intensity measure had to be either directly available or possible to derive from the publication by the data shown in tables or figures. In crossover trials, only data from studies with sufficient wash-out period (more than 2 weeks) between trials were used to avoid carry-over effects between trial stages.
For initial systemic review, the following data were extracted by an author (J. J. Song) in a structured fashion and then confirmed by another author (S. Vanneste): (1) study design, (2) patient characteristics (age, tinnitus laterality and tinnitus sound characteristics), (3) tDCS parameters (electrode placement, electrode size, current strength, duration of stimulation, duration of intermission between stimulations, number of treatment sessions, duration of wash-out period), and (4) results (percentage change in tinnitus loudness score, percentage of tDCS responders, any long-lasting beneficial effects). In case of missing or incomplete information, data were extracted from the figures and tables as much as possible.
From the systemic review data, weighted means for the percentage change in tinnitus intensity and percentage of tDCS responders were calculated. Additionally, provided we thought it clinically relevant, and no important clinical and methodological heterogeneity was found, we summarized results in a meta-analysis. In this way, the efficacy of tDCS was explored by calculating random model effect sizes (Hedges’
The meta-analysis was undertaken using Comprehensive Meta-Analysis (CMA) Version 2 software (Biostat, Englewood, New Jersey, USA).
An initial search using keywords “transcranial direct current stimulation” or “tDCS” screened a total of 714 articles. Adding another keyword “tinnitus” sorted out 17 articles from 714. Of 17, six studies that met the above-mentioned inclusion criteria were included in the systematic review and are summarized in Table
Summary of the 6 studies that were included in the current study.
Study | Group |
|
Anode | Cathode | Current, mA | Duration | Number of sessions | Measure | Mean percentage reduction | Percentage responders | Summary |
---|---|---|---|---|---|---|---|---|---|---|---|
Randomized controlled studies | |||||||||||
| |||||||||||
Fregni |
Active, anodal | 7 | LTA | R SO | 1 | 3 min | 2 | VAS tinnitus reduction scale (0–4) | 30.36% | 42.90% | |
Active, cathodal | 7 | R SO | LTA | 3 min | 2 | 0 | 0 | ||||
Sham | 7 | LTA | R SO | 5 sec | 2 | 0 | 0 | ||||
Faber |
Active, anode left | 8 | L DLPFC | R DLPFC | 1.5 | 20 min | 3 | VAS intensity, VAS distress | 27.80% | 8 weeks’ wash-out period between active and sham sessions changes measured directly after tDCS | |
Active, anode right | 7 | R DLPFC | L DLPFC | 1.5 | 20 min | 3 | 0.00% | NA | |||
Sham | 15 | 1.5 | 30 sec | 3 | 4.50% | ||||||
Garin |
Active, anode left | 20 | L LTA | R VLPFC | 1 | 20 min | 1 | VAS tinnitus reduction scale (0–4) | 9.13% | 35% | 2 weeks’ wash-out period between active and sham sessions |
Active, anode right | 20 | R VLPFC | L LTA | 1 | 20 min | 1 | 30% | ||||
Sham | 20 | L LTA | R VLPFC | 110 |
20 min | 1 | 0 | ||||
(or vice versa) | |||||||||||
| |||||||||||
Open label studies | |||||||||||
| |||||||||||
Vanneste et al. (2010) [ |
Active, anode left | 448 | L DLPFC | R DLPFC | 1.5 | 20 min | 1 | VAS intensity, VAS distress | 0 | 0.00% | Changes measured directly after tDCS |
Active, anode right | 30 | R DLPFC | L DLPFC | 1 | 7.95% | 29.90% | |||||
Vanneste et al. (2011) [ |
Active, anode right | 45 | R DLPFC | L DLPFC | 1.5 | 20 min | 1 | 14.00% | 46.67% | changes measured directly after tDCS | |
Frank |
Active, anode right | 32 | R DLPFC | L DLPFC | 1.5 | 30 min | 6 | THI, TQ, BDI, CGI | NA | 40.63% |
S.D.: standard deviation; LTA: left temporal area; SO: supraorbital; min: minutes; sec: seconds; VAS: visual analogue scale; DLPFC: dorsolateral prefrontal cortex; NA: not available; THI: tinnitus handicap inventory; TQ: tinnitus questionnaire; BDI: Beck depression inventory; CGI: clinical global impression scale.
Illustration of the steps of study selection.
The data of mean percentage responders to active tDCS were available in 2 RCT studies [
The data of mean percentage of tinnitus intensity reduction were available in 3 RCT studies [
The data of mean percentage responders to active tDCS were available in 2 LTA tDCS studies (all RCTs) [
The data of mean percentage of tinnitus intensity reduction were available in 2 LTA tDCS studies (all RCTs) [
As aforementioned, only RCTs were adopted for this meta-analytic comparison between active tDCS and sham tDCS with regard to tinnitus intensity reduction. As a result, only 2 of 3 RCTs were eligible for this meta-analysis. The pooled estimate of effect size (Hedges’
Forest plot of effect sizes (Hedges’
Model | Study name | Statistics for each study | Hedges’s g and 95% CI | ||||||
---|---|---|---|---|---|---|---|---|---|
Hedges’s |
Standard error | Variance | Lower limit | Upper limit |
|
|
|||
Fregni et al. (2006) [ |
0.936 | 0.531 | 0.282 | −0.104 | 1.976 | 1.764 | 0.078 |
| |
Garin et al. (2011) [ |
0.709 | 0.320 | 0.102 | 0.082 | 1.336 | 2.217 | 0.027 | ||
Random | 0.770 | 0.274 | 0.075 | 0.233 | 1.307 | 2.809 | 0.005 | ||
The current systemic review and meta-analysis indicate that overall 39.5% of the tinnitus patients responded to active tDCS with a mean tinnitus intensity reduction of 13.5%. Meanwhile, the comparison between LTA tDCS and bifrontal tDCS yields comparable results with regard to percent responders and percent reduction of tinnitus intensity. Additionally, although only 2 studies were included, meta-analysis showed that LTA tDCS was associated with a significantly better treatment outcome as compared with sham tDCS.
Although a meta-analytic approach to the mean percentage of the responders and the amount of tinnitus intensity reduction was impossible due to limited number of studies, the current systemic review of 6 studies revealed a 39.5% weighted mean response to tDCS and a 13.5% weighted mean reduction rate of the intensity.
TDCS has been used in treating other pathologies such as chronic pain or depression and meta-analytic approaches to reveal the treatment efficacy have recently been made. A recent systemic review and meta-analysis of 10 tDCS studies in the treatment of major depression has reported a weighted mean response rate of 19.8% to tDCS and weighted mean symptom severity reduction rate of 28.9% [
The weighted mean percentage of responders to active LTA and bifrontal tDCS were 37.0% and 40.2%, respectively. Additionally, the weighted mean percentage of tinnitus intensity reduction by active LTA and bifrontal tDCS were 14.6% and 13.1%, respectively. These very preliminary comparisons of the stimulation sites suggest that these 2 locations of active electrodes were comparably effective for tinnitus treatment.
The era of tDCS application to tinnitus patients has begun by Fregni et al. study that introduced anodal tDCS of the LTA resulting in a transient reduction of tinnitus, similar to 10-Hz TMS [
Meanwhile, bifrontal tDCS for tinnitus patients have first been introduced by Vanneste et al. [
In contrast to LTA-tDCS, bifrontal tDCS studies have demonstrated that switched polarity of the electrode pads was also effective for tinnitus management. That is, bifrontal tDCS placing the anodal electrode on the right DLPFC and the cathodal electrode on left DLPFC also could improve tinnitus intensity and tinnitus-related distress [
At this stage, the efficacy of tDCS in treating tinnitus patients cannot be confirmed because only 2 RCTs were eligible for meta-analysis. However, not only the 2 studies included yielded significant improvement in tinnitus intensity by active tDCS as compared with sham tDCS, but also all the studies included in the current systemic review demonstrated significant improvement of tinnitus intensity. Therefore, although supported by a limited number of studies, tDCS is a promising tool for tinnitus management, meriting further research.
No standard treatment protocol of tDCS in tinnitus management is available at the moment. Future RCTs in a large series of patients regarding the efficacy of tDCS as well as the comparison between LTA-tDCS and bifrontal tDCS are recommended to further validate the role of tDCS and to set up a standard treatment protocol.
The authors have no actual or potential conflicts of interest. This study was approved by the local ethical committee at Antwerp University Hospital and was in accordance with the declaration of Helsinki.
This research was supported by the Research Foundation Flanders (FWO), Tinnitus Research Initiative, TOP project University Antwerp.