New Therapies for Tinnitus

Abstract & Commentary

By Douglas Labar, MD, PhD, Professor of Neurology and Neruoscience, Weill Cornell Medical College. Dr. Labar reports no financial relationships relevant to this field of study.

Synopsis: It is recognized that most cases of chronic tinnitus are generated by central brain mechanisms that may be amenable to treatment with cognitive therapies and magnetic stimulation protocols of the temporal and frontal lobes.

Sources: Cima RF, et al. Specialized treatment based on cognitive behaviour therapy versus usual care for tinnitus: A randomized controlled trial. Lancet 2012;379:1951-1959. Plewnia C, et al. Treatment of chronic tinnitus with theta burst stimulation: A randomized controlled trial. Neurology 2012;78:1628-1634.

It is a sure sign that existing therapies are falling short when multiple new therapies are reported in close succession. Such is the case with tinnitus. Recent investigations have studied approaches such as combined sound-based and cognitive behavioral-based therapy, repetitive transcranial magnetic stimulation, transcranial direct current electrical stimulation, and electrical vagus nerve stimulation. Each has shown merit, and no clearly superior treatment has yet to emerge.

The principal approaches for tinnitus have been sound-based and cognitive behavioral-based therapies. Tinnitus retraining (sound-based) therapy involves a masking neutral sound and counseling sessions to reduce tinnitus annoyance. Cognitive behavioral therapy involves psycho-education and relaxation sessions, and is geared toward minimizing distress. Cima et al combined these approaches into a step-wise specialized treatment program, and compared that with less intense usual care.1

Randomization to specialized or usual care was carried out for 492 patients with tinnitus. Usual care, carried out by an audiology assistant, a clinical physicist in audiology, and a social worker, consisted of audiological diagnostics, audiological rehabilitation, and social work intake and follow-up interviews. Specialized care was similar, but added tinnitus education, psychology, and individual and group treatments, administered by a psychology assistant, clinical psychologist, movement therapist, physical therapist, and speech therapist. Patients were unaware of which of two treatments for tinnitus they were receiving, as were investigators assessing outcomes (which were measured up to 4 months after the last treatment).

At all follow-up time intervals, there were significant improvements in favor of specialized care on all outcome measures, such as health-related quality of life, emotional state, and tinnitus severity, impairments, catastrophising, and fear. It should be noted that these effects persisted long after the last therapy session. The results were similar in mild and severe tinnitus cases. However, older patients were more likely to be non-responders.

Perhaps not surprising is the result that aggressive, substantive, combined modality therapy for tinnitus is better than basic therapy. Nonetheless, this had not been demonstrated previously in a systematic way in a large population. Perhaps what is surprising is that these effects lasted so long after therapy was completed. Also to be mentioned is the likely high cost of the highly labor-intensive specialized care, as we consider other treatments.

Although repetitive transcranial magnetic stimulation (TMS) of the auditory cortex likely helps tinnitus, questions about this remain, particularly about stimulation settings. For example, Plewnia et al recently reported 4 weeks of daily bilateral theta burst TMS was no better than sham stimulation in 48 patients with chronic tinnitus, with outcomes being measured on the tinnitus questionnaire.2 Stimulation was delivered each working day, as a 3-pulse burst at 50 Hz cycling every 200 msec (5 Hz cycling) for 600 stimuli (total 2 minutes), which was then repeated 15 minutes later. However, previously this group reported a single 3-second burst of rTMS at 10 Hz over temporal and temporo-parietal cortex immediately reduced or eliminated subjective tinnitus in eight of 14 patients treated.3 Furthermore, they also previously reported a 2-week course of daily 1 Hz rTMS (30 minutes total duration) yielded improvement on the tinnitus questionnaire in five of six treated patients, with one patient remaining improved 2 weeks later.4

As just noted, in the work of Plewnia et al, tinnitus improvement did not even last for 2 weeks in five of their six treated patients.4 This should be contrasted with the beneficial results of the combined sound-based and cognitive behavioral-based therapies reviewed above,1 in which improvement seemed to persist for 4 months. However, other authors have reported long-lasing effects of rTMS of auditory cortex. Khedr et al found, in 62 patients treated with daily with 2000 pulses at 1 or 25 Hz, significant improvements remained as long as 10 months after therapy.5

Commentary

Perhaps evolving from the TMS results, research on transcranial direct current cortical stimulation (tDCS) for tinnitus recently has been undertaken. For example, 20 minutes of anodal stimulation targeting the left temporoparietal area significantly reduced tinnitus intensity and discomfort, immediately and at 1 hour follow-up, in a placebo-controlled study on 20 patients.6 Among 448 treated patients, 20 minutes of anodal right dorsolateral frontal cortex tDCS significantly reduced tinnitus-related distress and intensity.7

Finally, animal model work suggests vagus nerve stimulation (VNS) enhances auditory cortex plasticity in a way that may make it useful in tinnitus therapy.8 In rats, pairing VNS with repeated exposures to a high-pitched tone abnormally increased the proportion of auditory cortex neurons tuned to the frequency of that specific tone. Then, subsequent pairing of VNS with multiple other tones with slightly different frequencies reversed the abnormal excess tuning to the initial tone. Since tinnitus is thought in part to be due to abnormal auditory cortex neuronal hyperactivity, modifying this pathological process by administering VNS and different tones to patients with tinnitus may ameliorate their symptoms. This led MicroTransponder Inc. to conduct a proof-of-concept clinical trial in Belgium attempting to take advantage of the seeming plasticity-enhancing effects of VNS by pairing it with tones, as a new severe tinnitus therapy. Results were presented at the International Conference on Tinnitus in Bruges, Belgium, in June 2012.9 Among 10 patients treated for 4 weeks in this open-label pilot study, 40% were responders judged by the Tinnitus Handicap Index, and 70% were responders judged by the Iowa Tinnitus Handicap Questionnaire.

We now have evolving a number of new treatment approaches for tinnitus, a condition for which we had few treatment approaches previously. Hopefully, future research will help practitioners decide which treatment has the best efficacy and least adverse effects; what clinical patient features or diagnostic test findings predict the best results; with stimulation, what parameters and treatment schedule should be used; and what is the most effective use of our health care dollars.

References

1. Cima RF, et al. Specialized treatment based on cognitive behaviour therapy versus usual care for tinnitus: A randomized controlled trial. Lancet 2012;379:1951-1959.

2. Plewnia C, et al. Treatment of chronic tinnitus with theta burst stimulation: A randomized controlled trial. Neurology 2012;78:1628-1634.

3. Plewnia C, et al. Transient suppression of tinnitus by transcranial magnetic stimulation. Ann Neurol 2003;53:263-266.

4. Plewnia C, et al. Moderate therapeutic efficacy of positron emission tomography-navigated repetitive transcranial magnetic stimulation for chronic tinnitus: A randomized, controlled pilot study. J Neurol Neurosurg Psychiatry 2007;78:152-156.

5. Khedr E, et al. Contralateral versus ipsilateral rTMS of temporalparietal cortex for the treatment of chronic unilateral tinnitus: Comparative study. Eur J Neurol 2010;17:976-983.

6. Garin P, et al. Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation. J Neurol 2011;258:1940-1948.

7. Vanneste S, et al. Bilateral dorsolateral prefrontal cortex modulation for tinnitus by transcranial direct current stimulation: A preliminary clinical study. Exp Brain Res 2010;202:779-785.

8. Engineer ND, et al. Reversing pathological neural activity using targeted plasticity. Nature 2011;470:101-104.

9. Vanneste S, et al. Parie VNS for tinnitus — Pilot study results. Presented at International Conference on Tinnitus in Bruges, Belgium; June 2012.