Efficacy of repetitive transcranial magnetic stimulation for the treatment of refractory chronic tinnitus: a randomized, placebo controlled study. Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study. Effect of daily repetitive transcranial magnetic stimulation for treatment of tinnitus: comparison of different stimulus frequencies. Idiopathic Subjective Tinnitus Treated by Amitriptyline Hydrochloride/Biofeedback. Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Outcomes of clinical trial: tinnitus masking versus tinnitus retraining therapy. Neuromonics Tinnitus Treatment: third clinical trial. Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy. High-frequency pulsed electromagnetic energy in tinnitus treatment.
The pathophysiologic mechanisms of idiopathic tinnitus remain unclear. Low frequency rTMS applied over the auditory cortex has been proposed as a new and causally oriented treatment approach for pathological conditions with abnormal, increased cortical activity including tinnitus with increased activity in the auditory cortex. However available studies are characterized by a positive reports on the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) for treatment of tinnitus, there are few details about the duration of specific treatment effects.
                The design of the study was randomized, prospective, placebo-controlled. Right-handed patients were treated with either real or sham 1 Hz frequency rTMS over a period of two weeks. Fifty-two patients with chronic, treatment resistant tinnitus and stable medication were enrolled in the study after giving written informed consent and forty-two patients completed the study and were included in data analysis.
                The ability to reduce the symptoms of tinnitus appeared in both randomized groups immediately after the 1 Hz rTMS and sham stimulation phase. There was a significant reduction in both groups of the tinnitus total score on the Tinnitus Handicap Inventory (THI) (real rTMS p=0.005; sham rTMS p=0.049) and Tinnitus Questionnaire (TQ) total score (real rTMS p=0.003; sham rTMS p=0.049). On the THI evaluation scale, in the real rTMS a mild worsening was noted during week 6 in comparison with the state attained in week 2. During the subsequent course of the study a significant reduction of the total score persisted in the case of THI (real rTMS week 14 p=0.033 and borderline week 26 p=0.058). The reduction of symptoms as evaluated using the TQ was significant compared to baseline in the real rTMS group at week 2, 6 and 14 (p=0.003; p=0.024; p=0.022). The group treated with sham stimulation reached significant reduction of symptoms only at week 2 (p=0.049). A comparison of the difference in the recorded values of the total score during follow-up in relation to baseline expressed as a percentage demonstrates the difference in the effect of rTMS and sham stimulation as evaluated by both the basic scales. Graphical analysis of mean patterns of treatment response according to stimulation type shows a similarity between treatment response patterns evaluated by reduction of the total scores using THI and TQ.
                The principal finding of this study is that real 1 Hz rTMS treatment was capable of significantly reducing the total baseline score of basic scales that measure tinnitus severity. This result is important as it proves that significant reduction of symptoms can be achieved even in a group of patients with long-term symptoms resistant to pharmacological treatment. Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing.
                Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS.
                After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS.
                These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex. We compared the effect of different frequencies of repetitive transcranial magnetic stimulation (rTMS) (1 Hz, 10 Hz, 25 Hz and sham (occipital, 1 Hz)), given daily over the left temporoparietal cortex for 2 weeks, on 66 patients with chronic tinnitus randomly divided into four treatment groups. Patients were assessed using the Tinnitus Handicap Inventory, self-ratings of symptoms and audiometric measures of residual inhibition before, immediately after 2 weeks' treatment and monthly thereafter for 4 consecutive months.
                There were no significant differences in basal measures between the four groups of patients. A two-factor ANOVA revealed a significant "rTMS" x "time" interaction for all measures. This was because real rTMS produced greater improvement than sham. However, there was no significant difference between the responses to different frequencies of rTMS. The response to rTMS depended on the duration of tinnitus: patients who had tinnitus for the longest period of time were the least likely to respond to treatment.
                Daily sessions of rTMS over the temporoparietal cortex may be a useful potential treatment for tinnitus. The efficiency of two treatment modalities for subjective/idiopathic tinnitus (SIT): biofeedback (BF) and amitriptyline hydrochloride (AT) was investigated in 225 randomly selected subjects. Findings show that after 10 weeks of treatment in the BF group, 43.5% of the patients reported an improvement of tinnitus during activity. In the AT group, 27.5% of patients reported subjective improvement of tinnitus at rest although only 15.8% of the AT patients reported improvement during activity. Biofeedback during rest had a significantly better effect on tinnitus disturbance than AT. No objective diminishment of tinnitus loudness was found as a result of any of the treatment modalities. We believe that BF can help tinnitus patients especially during periods of rest and we also suggest trying tricyclic antidepressant drugs such as AT for treatment of tinnitus patients, in small doses, however, to minimize the side effects of this drug. Subjective tinnitus (ST) is one of the most common and yet most unclear of otologic symptoms.(1-4) ST can accompany any type of hearing loss including both sensorineural as well as conductive hearing loss, and may originate from any part of the auditory pathway.(1,5) Treatment of ST must be primarily directed to the basic illness diagnosed after a thorough general ear-nose-throat and neurologic evaluation.(6) Severity of ST is evaluated both objectively, by determining the pitch and intensity of the tinnitus,(7) and subjectively as described by the patient. Because of the relatively high incidence of ST and in some patients, the severe personal reaction to it, many different treatments have been suggested, but generally only small to moderate success has been achieved in reducing tinnitus and its consequences, if any at all.(8) In this study we examined the effect of two treatment modalities: amitriptyline hydro-chloride and biofeedback. In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency > 1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency < or = 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression. A controlled clinical study was conducted to evaluate prospectively the clinical efficacy of tinnitus masking (TM) and tinnitus retraining therapy (TRT) in military veterans having clinically significant tinnitus. Qualifying patients were placed into the two groups in an alternating manner (to avoid selection bias), and treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index) and the verbally administered TRT interview forms. Findings are presented from the three written questionnaires, and from two of the interview questions (percentage time aware of, and annoyed by, tinnitus). Outcomes were analyzed on an intent-to-treat basis, using a multilevel modeling approach. Of the 123 patients enrolled, 118 were included in the analysis. Both groups showed significant declines (improvements) on these measures, with the TRT decline being significantly greater than for TM. The greater declines in TRT compared to TM occurred most strongly in patients who began treatment with a "very big" tinnitus problem. When patients began treatment with a "moderate" tinnitus problem, the benefits of TRT compared to TM were more modest. The Neuromonics Tinnitus Treatment combines the use of a novel approach to acoustic stimulation with a structured program of counseling and support by a clinician specifically trained in tinnitus rehabilitation. The distinctive acoustic component has been designed to provide stimulation to auditory pathways deprived by hearing loss, engage positively with the limbic system, and allow intermittent, momentary tinnitus perception within a pleasant and relaxing stimulus, thereby facilitating desensitization to the tinnitus signal. The purposes of this study were (1) to demonstrate the efficacy of the treatment, when enhanced with various modifications since previously reported trials and (2) to test the relative clinical effectiveness of two variations of the approach. In the first, intermittent tinnitus perception was facilitated throughout treatment through the use of a stimulus in which intensity peaks allowed the patients' tinnitus perception to be completely covered up, whereas in the intensity troughs their tinnitus was briefly discernible. In the second, subjects experienced little tinnitus perception while listening to the treatment for the first 2 mo, then experienced intermittent perception.
                Thirty-five subjects with a predominantly moderate to severe level of tinnitus-related distress before treatment were randomly allocated into one of two treatment groups, corresponding to the two stage-based variations of the Neuromonics Tinnitus Treatment. Participants were provided with a high-fidelity personal sound player with earphones and an acoustic stimulus that had been spectrally modified according to their individual audiometric profile. They were instructed to use the acoustic stimulus for at least 2 hr per day, particularly at those times when their tinnitus was usually disturbing. Each group had equal amounts of clinician time for education, monitoring, and support.
                At 2, 4, 6, and 12 mo after commencing treatment, both groups displayed clinically and statistically significant improvements in tinnitus distress, awareness, and minimum masking levels as well as loudness discomfort levels. Improvements increased with time over the first 6 mo of therapy, at which time 91% of all subjects across the two groups reported an improvement in tinnitus disturbance (as measured by the Tinnitus Reaction Questionnaire) of at least 40%, with a mean improvement of 65%. Also, 80% of subjects at 6 mo reported a level of tinnitus disturbance that was no longer clinically significant. There was some indication of a more consistent benefit over 12 mo for the group that was provided initially with a high level of tinnitus interaction; however, inter-group differences were not statistically significant. A relation between reported treatment usage (hours per day) and clinical outcomes was observed, suggesting that a "dosage effect" may apply with the stimulus provided.
                This study found that the Neuromonics Tinnitus Treatment provides rapid and profound improvements to the severity of tinnitus symptoms and their effect on the subject's quality of life. This was a consistent effect, provided by a treatment that subjects reported as being pleasant to use. Both of the stage-based variations of the treatment that were tested in this study were shown to be successful in achieving these outcomes. To assess, using a double-blind procedure, the pain-relieving effects of rTMS against placebo, and their predictive value regarding the efficacy of implanted motor cortex stimulation (MCS).
                Three randomised, double-blinded, 25 min sessions of focal rTMS (1 Hz, 20 Hz and sham) were performed in 12 patients, at 2 weeks intervals. Effects on pain were estimated from daily scores across 5 days before, and 6 days after each session. Analgesic effects were correlated with those of subsequent implanted motor cortex stimulation (MCS).
                Immediately after the stimulating session, pain scores were similarly decreased by all rTMS modalities. Conversely, during the following week, 1 Hz stimulation provided significantly less analgesia than 20 Hz and placebo, and was pro-algesic in some patients. Placebo and 20 Hz rTMS were effective on different patients, and only 20 Hz rTMS predicted the efficacy of subsequent MCS, with no false positives.
                While 1Hz rTMS should not be used with analgesic purposes, high-frequency rTMS may become useful to select candidates for MCS. Placebo effects are powerful and should be controlled for. Immediate results after a single rTMS session are misleading.
                Defining rTMS parameters is a crucial step before proposing rTMS as predictive test of SCM efficacy in clinical practice. Electromagnetic therapy has been used with reported success in multiple clinical settings, including the treatment of seizure disorders, brain edema, migraine headaches, revascularization of burn wounds, and diabetic ulcers. The purpose of the study was to investigate the effect of pulsed high-frequency electromagnetic therapy on chronic tinnitus.
                A randomized, prospective, double-blind, placebo-controlled pilot study was conducted to evaluate the effectiveness of high-frequency pulsed electromagnetic energy using the Diapulse device in the treatment of chronic tinnitus. Thirty-seven adult patients with chronic tinnitus of at least 6 months' duration were recruited and randomly assigned to either a treatment or a placebo group.
                Patients received 30-minute treatments with the Diapulse device three times a week for 1 month. The unit was set to deliver electromagnetic energy at a frequency of 27.12 MHz at a repetition rate of 600 pulses per second. All subjects had pretreatment and post-treatment audiological testing, including tinnitus frequency and intensity matching. They responded to a tinnitus rating questionnaire and the Tinnitus Handicap Inventory before and after treatment.
                There was no significant change in the pretreatment and post-treatment audiometric thresholds in either group. There were no significant differences between the pretreatment and post-treatment Tinnitus Handicap Inventory scores or the tinnitus rating scores in either subject group (Student t test). No diagnosis-specific differences were identified.
                High-frequency pulsed electromagnetic energy (Diapulse) at the settings used in the study showed no role in the therapy of patients with chronic tinnitus.
There is very limited support for the use of low-frequency rTMS for the treatment of patients with tinnitus. When considering the impact of tinnitus on patients' quality of life, support is from a single study with a low risk of bias based on a single outcome measure at a single point in time. When considering the impact on tinnitus loudness, this is based on the analysis of pooled data with a large confidence interval.
Studies suggest that rTMS is a safe treatment for tinnitus in the short-term, however there were insufficient data to provide any support for the safety of this treatment in the long-term.
More prospective, randomised, placebo-controlled, double-blind studies with large sample sizes are needed to confirm the effectiveness of rTMS for tinnitus patients. Uniform, validated, tinnitus-specific questionnaires and measurement scales should be used in future studies.