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.
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.
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.