Idiopathic Subjective Tinnitus Treated by Amitriptyline Hydrochloride/Biofeedback. The assessment of lamotrigine, an antiepileptic drug, in the treatment of tinnitus. Efficacy of repetitive transcranial magnetic stimulation for the treatment of refractory chronic tinnitus: a randomized, placebo controlled study. Treatment of idiopathic sudden sensorineural hearing loss with antiviral therapy: a prospective, randomized, double-blind clinical trial. Antiviral treatment of idiopathic sudden sensorineural hearing loss: a prospective, randomized, double-blind clinical trial. An experimental evaluation of the effects of transcutaneous nerve stimulation (TNS) and applied relaxation (AR) on hearing ability, tinnitus and dizziness in patients with Menière's disease. Treatment of tinnitus with gabapentin: a pilot study. The tricyclic trimipramine in the treatment of subjective tinnitus. Efficacy of amitriptyline in the treatment of subjective 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. Tinnitus is an extremely prevalent condition that currently has no satisfactory clinical treatment. Development of therapy has been hampered by the diversity of underlying conditions that give rise to the symptom of tinnitus. A drug that has multiple actions may have an improved chance of being effective. One such drug is lamotrigine, a recently developed antiepileptic agent that has both glutamate release inhibition and sodium channel antagonist activity.
                Lamotrigine was evaluated in a double-blind, placebo-controlled, crossover clinical trial. Patients initially were tested with an intravenous infusion of lidocaine (10 mg/mL) to a maximum of 100 mg or until a reduction in tinnitus. Lamotrigine or placebo tablets were taken once daily (25 mg) for 2 weeks, 50 mg for 2 weeks, and 100 mg for 4 weeks.
                Patients were chosen from among volunteers from the tinnitus clinic in the local hospital without reference to underlying pathology.
                Those patients whose tinnitus had been present for less than 6 months or whose tinnitus was likely to vary spontaneously were excluded.
                Perceived intensity and intrusiveness of tinnitus was assessed before entry onto the trial and at 4-week intervals throughout the trial.
                Assessment comprised questionnaires, visual analog scales, and a battery of audiologic measurements.
                There was no correlation between the response to lidocaine and the response to lamotrigine. There was good agreement between the questionnaires and visual analog scales in the reporting of perceived changes; however, this was not reflected as changes in the audiologic tests.
                Of the 31 participants who completed the trial, questionnaires indicated that lamotrigine was effective in a very few of these persons. 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. A subclinical viral labyrinthitis has been postulated in the literature to elicit idiopathic sudden sensorineural hearing loss (ISSHL). An etiologic role for the herpes family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, we evaluated the therapeutic value of the antiherpetic drug acyclovir (Zovirax) on hearing recovery in 91 patients with ISSHL who received prednisolone in a prospective, randomized, double-blind, placebo-controlled, multicenter trial. The audiometric parameters included pure tone and speech audiometry. Subjective parameters studied included hearing recovery, a pressure sensation in the affected ear, vertigo, and tinnitus. A 1-year follow-up was obtained. Hearing recovery for the whole group averaged about 35 dB and was independent of the severity of the initial hearing loss or vestibular involvement. Speech audiometry improved from 49% to 75%. After 12 months, pressure sensation and vertigo decreased to 15.6% (acyclovir) and 10.3% (placebo) and 12.5% (acyclovir) and 10.7% (placebo), respectively. Tinnitus decreased slightly, to 46.9% (acyclovir) and 55.2% (placebo), in the same period (p > .05 for all parameters). We conclude that no beneficial effect from combining acyclovir with prednisolone can be established in patients with ISSHL. A subclinical viral labyrinthitis has been postulated in the literature to elicit Idiopathic Sudden Sensorineural Hearing Loss. An etiological role for the herpes virus family is assumed. Corticosteroids possess a limited beneficial effect on hearing recovery in ISSHL. In this study, the therapeutic value of the antiherpetic drug aciclovir (Zovirax) on hearing recovery in 44 ISSHL patients receiving prednisolone is evaluated in a multicentre clinical trial. The study is designed prospectively, randomized, double-blind and placebo-controlled. Subjective parameters include hearing recovery, a pressure sensation on the affected ear, disequilibrium or vertigo and tinnitus. Audiometric parameters include pure tone and speech audiometry. A one-year follow up is obtained. Both the pressure sensation and disequilibrium or vertigo have a good prognosis, but tinnitus, occurring in most patients, has a poor prognosis. Hearing recovery prognosis depends on the severity of initial hearing loss, and not on vestibular involvement. No beneficial effect from combining aciclovir with prednisolone can be established in ISSHL. In 20 patients diagnosed with Menière's disease, transcutaneous nerve stimulation (TNS) and applied relaxation (AR) were used as a treatment aimed at reducing tinnitus and dizziness and increasing hearing ability. The main aim of the study was to examine whether TNS could be regarded as a more beneficial treatment regimen than AR. An experimental between-group cross-over design was used. The results from the experimental phase (group comparisons) showed a significantly increased ability to hear for the TNS group when measured on visual analogue scales. During the same period, the AR-group showed a significant hearing improvement for the ear not primarily affected by Menière's disease as measured with pure tone audiometry. The vestibular tests did not reveal any significant changes either after TNS or AR intervention. Tinnitus matching showed changes of pitch and loudness before and after both TNS and AR intervention. However, no statistically significant changes between treatment regimes were found on these measures. The results from this study did not show TNS to be superior to AR in reducing tinnitus, dizziness or increasing hearing ability. To evaluate the effectiveness of gabapentin (Neurontin) improve the disease-specific quality of life in patients with moderate tinnitus.
                Randomized, double blind, placebo-controlled clinical trial.
                Single-center academic outpatient otolaryngology practice.
                Gabapentin 1800 mg daily versus placebo.
                The study design is a randomized, double blind placebo controlled single site trial conducted in an academic medical center. Inclusion criteria included patients between ages 18 and 70 with a complaint of nonpulsatile, subjective tinnitus, bilateral or unilateral, greater than 3 months in duration. The primary outcome measure is the Tinnitus Handicap Inventory; secondary measures include the Profile of Mood States (POMS) rating scale, subjective tinnitus severity. The null hypothesis addressed in this study is that the drug would not result in significant alleviation of the symptom of tinnitus.
                Seventy-six patients completed the trial; of these 52 received the drug. No significant differences were found between the two groups after 5 weeks of treatment with gabapentin.
                There is insufficient evidence to support the effectiveness of gabapentin in the treatment of tinnitus. We examined 26 consecutive patients with subjective tinnitus. All subjects were treated with the tricyclic antidepressant trimipramine in a double-blind study, each subject acting as his own control. All subjects were evaluated with pure tone audiometry, site of lesion testing, and auditory brain stem evoked response. The tinnitus assessment consisted of frequency and intensity matching, the determination of masking levels, and a subjective evaluation of severity. Plasma levels of trimipramine were monitored at regular intervals, and the Zung and Millon inventories were administered at the beginning and end of each study period. Nineteen subjects completed the study. Within the trimipramine group, one reported complete disappearance of his tinnitus, eight reported improvement, three no change, and seven that tinnitus was worse. Within the placebo group, eight reported improvement, seven no change, and four that tinnitus was worse. The natural history of tinnitus is such that what has been observed may reflect the evolution of the disease itself, rather than the effect of treatment. We feel that while tricyclics may not have been shown to be effective, the placebo effect played a significant role in the results obtained. We investigated the effect of amitriptyline, a tricyclic antidepressant, on patients with subjective tinnitus. The study group consisted of 37 adult patients admitted to the Ear, Nose, and Throat and Audiology Department of Hacettepe University. The amitriptyline group consisted of 20 patients and the placebo group consisted of 17 patients. All of the patients were evaluated using a questionnaire, audiologic evaluation, high-frequency audiometry, impedancemetric tests, auditory brainstem response, tinnitus frequency, and loudness matching assessed by audiometric methods at the beginning and end of the study. The patients in the amitriptyline group received 50 mg/day amitriptyline in the first week and 100 mg/day for the following 5 weeks. In the placebo group, the patients received tablets consisting of lactose starch for 6 weeks, with a dosage of 1 tablet/day. The subjective complaints of the patients in the amitriptyline group decreased, and the "present" symptoms resulted in fewer complaints. The severity of tinnitus decreased in the amitriptyline group by means of subjective and audiometric methods. In the placebo group, no significant change was observed. The success of treatment was 95% in the amitriptyline group and 12% in the placebo group. Amitriptyline therapy was concluded to be effective.
Current evidence regarding the effectiveness of anticonvulsants in patients with tinnitus has significant risk of bias. There is no evidence from studies performed so far to show that anticonvulsants have a large positive effect in the treatment of tinnitus but a small effect (of doubtful clinical significance) has been demonstrated.