Table 2. Literature review summary of tinnitus treatment or investigation by rTMS.
Note all studies used a Figure of 8 TMS coil except for De Ridder et al. (2005), which used a circular coil and Vanneste et al. (2011), which used a double cone coil. AC, auditory cortex; AMT, active motor threshold; B, bilateral tinnitus; BDI, Beck depression inventory; BDI-II, Beck depression inventory, second edition; BSI-18, 18-item brief symptom inventory; CGI, clinical global impression scale; CT, computed tomography; cTBS, continuous theta burst (3 50Hz pulses at 5Hz); D, diagnostic; fMRI, functional magnetic resonance imaging; IAF, individual alpha frequency (50, frequency ranging between 8 and 12 Hz); imTBS, intermediate theta burst (75 50Hz pulses at 0.06Hz); iTBS, intermittent theta burst (3 50Hz pulses at 0.1Hz); ITI, intertrain interval; L, left-sided tinnitus; LAC, left auditory cortex; LTA, left tempoparietal area; LTC, left tempoparietal cortex; LTG, left temporal gyrus; MEG, magnetoencephalography; MPA, mesial parietal area; MRI, magnetic resonance imaging; MT, motor threshold; NR, not reported; PET, positron emission tomography; PET-CT, positron emission tomography-computed tomography; R, right-sided tinnitus; RAC, right auditory cortex; RMT, resting motor threshold; RSTG, right superior temporal gyrus; RTC, right tempoparietal cortex; rTMS, repetitive transcranial magnetic stimulation; SPECT, single photon emission computed tomography; T, therapeutic; THQ, tinnitus handicap score; TPJ, tempo-parietal junction; TSIQ, tinnitus severity index questionnaire; TQ, tinnitus questionnaire; U, unilateral tinnitus; VARL, ear-specific visual analogue rating of tinnitus loudness; VAS, visual analog scale
| Author (Year) | # of Subjects (Age Range) | Tinnitus Laterality | Drug Therapy details | rTMS Protocol [Therapeutic or Diagnostic] | Coil Position | MRI Navigation | Sham Method | Adverse Events details | Tinnitus Outcome Measure | # Responders (% total) comments |
|---|---|---|---|---|---|---|---|---|---|---|
| Eichhammer P, et al. (2002) | 3 (48–62) | 2B 1 L |
No | [LF] 5 days of (1Hz × 33.3 min) = 2000 pulses/day @ 110% MT [D] |
AC based on PET | Yes | Sham Coil | Aggravation of tinnitus (n = 1) Two days of tinnitus worsening followed by a dramatic reduction in tinnitus. |
TQ PET |
3(100%) |
| Plewnia C, et al. (2003) | 14 (35–59) | 12 B 2 L |
NR | [HF] 1 day of (10 Hz × 3s × 5 per each of 12 scalp positions) w/30s inter train interval = 1800 pulses @ 120% MT [D] |
12 scalp positions based on 10–20 EEG setup | No | None | NR Aggravation of tinnitus (n = 1) |
Self-rating scale (1– 4) | 8 (57%) with left temporal or temporoparietal stimulation |
| Langguth B, et al. (2003) | 1 (62) | 1 B | No | [LF] 20 days of (1Hz × 33.3 min) = 2000 pulses/day @ 110% MT [D] |
AC based on PET | Yes | Sham Coil | NR Aggravation of tinnitus (n = 1) Two days of tinnitus worsening followed by a dramatic reduction in tinnitus. |
TQ | 1(100%) |
| De Ridder D, et al. (2005) | 114 (Not Reported) | 106 U 8 B |
NR | [LF/HF] 1 day with 200 pulses of 1, 3, 5, 10, and 20 Hz = 1000 pulses @ 90% MT [T] |
AC contralateral to tinnitus site based on fMRI | Yes | Coil positions, coil perpendicular to the skull | NR | VAS | 28 (24.5%) 32 (28%) additional had a partial response |
| Kleinjung T, et al. (2005) | 14 (20–62) | 2 B 6 L 6 R |
No | [LF] 5 days of (1 Hz × 33min) = 2000 pulses @ 110% MT [T] |
12 LAC and 2 RAC based on PET | Yes | Sham Coil | None | TQ | 8 (57%) |
| Fregni F, et al. (2006) | 7 (44–68) | 7 B | NR | [HF] 1 day of (10 Hz × 3s × 9 trains) w/5min inter train interval =270 pulses @ 120% MT [T] |
LTA and MPA based on 10–20 EEG system | No | Sham Coil | None | Self-rating scale (1– 4) | 3 (42%) with LTA stimulation |
| Folmer RL, et al. (2006) | 15 (44–71) | 7 L 8 R |
No | [HF] 1 day of (10 Hz × 3s × 5 sessions w/57s intertrain interval) = 150 pulses @ 100% MT [D]-[T] |
LTC and RTC based on 10–20 EEG system | No | Coil with recorded sounds of actual TMS | NR | Self-rating scale (1– 10) | 6 (40%) 5 (33.3%) with LTC stimulation, 1 (6.6%) with RTC stimulation |
| Richter GT, et al. (2006) | 1 (43) | 1 B | NR | [LF] 5 days of (1 Hz × 30s w/1 day inter train interval) = 1800 pulses @ 110% MT [D]-[T] |
RAC based on PET-CT | No | None | None | PET-CT Tinnitus severity questionnaire with analogue scale |
1 (100%) |
| Londero A, et al. (2006) | 13 (22–64) | 10 L 3 R |
No Patients had undergone previous treatment with antiepileptics. |
[LF/HF] 1 day of (10 Hz × 3s followed by 1 Hz × 20min) = 1230 pulses @ 120% MT [T] |
AC contralateral to tinnitus site based on fMRI | No | None | NR Aggravation of tinnitus (n = 1) Aggravation lasting for10 days |
THQ |
6(46%) with 1 Hz stimulation 1(7.7%) with 10 Hz stimulation |
| Langguth B, et al. (2006) | 28 (38–65) | 13 B 9 L 6 R |
NR | [LF] 10 days of (1 Hz × 33min) = 2000 pulses/day @ 110% MT [T] |
LAC based on 10–20 EEG system | No | None | Aggravation of tinnitus (n = 2) | TQ | 19 (67%) |
| Nowak DA, et al. (2006) | 1 (27) | 1 U | No | [LF] 5 days of (1 Hz × 18min) = 1080 pulses/day @ 90% MT [T] |
LAC | No | None | GTC seizure (n = 1) | NR | 0 (0%) |
| De Ridder D, et al. (2007) | 46 (>18) | 46 U | NR | [HF] 1 day of tonic rTMS with 200 pulses at5, 10, and 20 Hz = 600 pulses followed by a second day of burst rTMS at 5, 10, and 20 Hz Hz both @ 90% MT [T] |
AC contralateral to tinnitus site | No | Coil positions, coil perpendicular to the skull | NR | VAS TQ |
14 (30.4%) 5 (10.9%) with 5Hz 2 (4.3%) with 10Hz 7 (15.2%) with 20Hz |
| Plewnia C, et al. (2007a) | 9 (49–68) | 8 B 1 R |
Yes Lidocaine (1.5 mg/kg) i.v. |
[LF] 2 days of (1 Hz × 5, 15, and 30min w/30 min inter train interval) = 3000 pulses/day @ 120% MT [D]-[T] |
Based on PET scan results | Yes | Occipital control position | Aggravation of tinnitus (n = 1) Tinnitus increased after 5 minutes stimulation and returned to baseline after 30 mins. |
VAS | 6 (66%) |
| Plewnia C, et al. (2007b) | 6 (49–68) | 6 B | No | [LF] 20 days of (1 Hz × 30min) = 1800 pulses/day @ 120% MT [T] |
Based on PET scan results | Yes | Occipital control position | None | TQ | 5 (83%) |
| Kleinjung T, et al. (2007) | 45 (20–69) | 30 B 8 L 7 R |
NR | [LF] 10 days of (1 Hz × 33 mins) = 2000 pulses/day @ 110% MT [T] |
AC based on fMRI | Yes | None | NR | TQ | 18 (40%) |
| Rossi S, et al. (2007) | 16 (only 14 completed) (35–72) | 7 B 4 L 3 R |
No | [LF] 5 days of (4 trains of (1Hz × 6.66 mins w/ITI of 30s)) = 1200 pulses/day @ 120% MT [T] |
LTC based on PET or AC based on 10–20 EEG system | Yes | Coil positioned 45° from the skull | Aggravation of tinnitus (n = 2) Slight headache or tongue paraesthesia |
VAS | 8(57%) |
| Smith JA, et al. (2007) | 4 (30–60) | 4 B | No | [LF] 5 days of (1 Hz × 30 mins) = 1600 pulses/day @ 110% MT [D] |
Primary AC based on PET/CT | Yes | Coil positioned 45° from the skull | None | PET TSIQ VAS |
NR TSIQ and VAS scores decreased, but were not considered statistically significant. |
| Lee SL, et al. (2008) | 8 (57–85) | 8 B | NR | [LF] 5 days of (0.5 Hz × 20 min) = 600 pulses/day @ 100% MT [T] |
LTC, but method of finding area NR | No | None | Jaw Soreness (n =1) Photophobia (n=1) Restlessness (n=1) Imbalance (n=1) |
THI | 1 (12.5%) |
| Mennemeir M, et al. (2008) | 1 (44) | 1 B | No | [LF] 10 days of (1 Hz × 30 min) = 1800 pulses/day @ 110% MT [T] |
Anterior RSTG based on PET | Yes | Coil positioned 45° from the skull | None | PET-CT VAR |
1 (100%) |
| Kleinjung T, et al. (2008) | 16 (41–60) | 27 B 3 L 2 R |
NR Patients had previously been on vasodilators and anti- depressesants as possible tinnitus treatment. |
[LF]-[HF] 1 day of (1 Hz × 33 min) = 2000 pulses/day @ 110% MT 1 day of (20 Hz × 50s) followed by (1 Hz × 16min) = 2000 pulses/day @ 110% MT [D] |
Neuronavigation to LAC | Yes | None | None | TQ |
3 (18.75%) with 1Hz 8 (50%) with 50Hz/1Hz |
| Khedr EM, et al. (2008) | 50 (6 mo – 25yrs) | 12 B 22 R 32 L |
No | [LF]-[HF] 10 days of either 1, 10, 25 Hz @ 100% RMT (90% RMT for 25 Hz) [T] |
LTC based on 10– 20 EEG system | No | Occipital control position | NR | THI | 38 (76%) 13 (26%) with 1Hz 13 (26%) with 10Hz 12 (24%) with 25Hz |
| Garcia-Toro M, et al. (2009) | 1 (73) | 1 B | Yes Trimetazidine (60mg daily) although period of treatment NR. |
[LF] 34 pulse trains (1 Hz × 60s) = 2040 pulses/day at 100% MT [T] |
LTC based on 10– 20 EEG system | No | None | Facial twitching (n =1) | Self Rating Scale (0–100) HDS |
1 (100%) |
| Kleinjung T, et al. (2009) | 32 (35–56) | 12 B 9 L 11 R |
Yes 16 patients received levodopa (100mg) and benserazide (25mg) |
[LF] 10 days of (1 Hz × 33.3 mins) =2000 pulses/day @ 110%MT [D]-[T] |
Neuronavigation to LAC | Yes | None | None | TQ | NR TQ scores in both control and levodopa groups. No significant difference between groups and only the control group had a significant lasting suppression during the follow-up period |
| Marcondes RA, et al. (2009) | 10 (>18) | NR | No | [LF] 5 days of (1 Hz × 17min) = 1020 pulses/day @110% MT [D]-[T] |
LTC based on 10– 20 EEG system | No | Sham Coil | None | THI VAS SPECT |
NR Active rTMS showed significant reduction in tinnitus outcome measures as compared to Sham rTMS. |
| Meeus O, et al (2009) | 50 (22–78) | 26 B 24 U |
NR | [LF/HF] 1 day of 1, 5, 10, and 20 Hz tonic stimulation for 200 pulses followed by 5, 10, or 20 Hz burst stimulation (50 or 100 Hz bursts with either 3, 5, or 10 pulses) for 200 pulses = 400 pulses/day @ 50% MO [D] |
AC contralateral to the tinnitus, 5 cm above the entrance of the external auditory meatus on straight line to the vertex | No | Coil positioned 45° from the skull | NR | VAS | NR Active rTMS showed a significant reduction in tinnitus outcome measures as compared to Sham rTMS. 1 Hz stimulation was significantly better at reducing tinnitus than high frequency stimulation. |
| Poreisz C, et al. (2009) | 33 (only 20 completed the trial) (35–60) | 12 B 4 L 4 R |
No | [HF] cTBS, iTBS, or imTBS separated by 5 days for 600 pulses at 80% AMT (6 patients) or 80% RMT (14 patients) [D] |
LTC based on 10– 20 EEG system | No | None | Headache (n = 2) Unpleasant feeling (n = 5) Aggravation of tinnitus (n = 3) |
TQ VAS |
11 (55%) |
| Soekadar SR, et al. (2009) | 1 (54) | 1B | Yes Prior treatment with antidepressants. Mirtazapine 45 mg/day started 4 weeks before treatment and maintained through treatment. |
[HF] 15 days of ((cTBS × 40s train) × 30 mins) × 1 or 2 times/day =18,000 –36,000 pulses/day @ 80% AMT [T] |
LTC and/or RTC based on 10–20 EEG system | No | None | NR | TQ VAS |
1(100%) |
| Anders M, et al. (2010) | 26 (20–69) | 13 B 3 L 6 R |
No | [LF] 10 days of (1 Hz × 25 mins) =1500 pulses/day @ 110% RMT [T] |
Neuronavigation to LAC | Yes | Coil positioned 45° from the skull | Aggravation of tinnitus (n = 2) Neck muscle contractions (n = 1) Transient headache, mild tongue paresthesia, transient worsening of tinnitus, and changes in sleep quality also reported. |
THI TQ VAS |
NR Active rTMS was capable of significantly reducing the total baseline score of basic scales that measure tinnitus severity. |
| Frank E, et al. (2010) | 1 (61) | 1 R | NR | [LF]-[HF] 10 days of (1Hz × 16min) = 2000 pulses/day @ 110% MT 1 day of: −5 Hz tonic; 10 Hz tonic; 20 Hz tonic = 100 pulses/day @ 110% MT−cTBS for 100 pulses/day @ 110% MT −10 Hz burst (3 stimuli with a frequency of 100 Hz) = 100 pulses/day @ 110% MT −20 Hz burst (5 stimuli with a frequency of 500 Hz) = 100 pulses/day @ 110% MT 10 days of (40 trains of 50 bursts (5 stimuli at 500Hz) w/ITI 25s) = 2000 pulses/day @ 110% MT [T] |
Based on PET scan results | Yes | Yes, but not detailed. | NR | TQ CGI |
1(100%) With 1 Hz and 20 Hz burst stimulation. |
| Khedr EM, et al. (2010) | 62 (26–55) | 30 L 32 R |
No | [LF]-[HF] 10 days of either ipsilateral or contralateral stimulation using: −1 Hz =2000 pulses/day @ 100% RMT −25 Hz for 40 trains × 50 pulses w/5s ISI = 2000 pulses/day @ 90% RMT [T] |
LTC or RTC based on 10–20 EEG system | No | None |
LF Headache (n = 21) Neck Pain (n = 14 ) Jaw Pain (n = 16) HF Headache (n = 19) Neck Pain (n = 10) Jaw Pain (n = 7) |
THI VAS |
43 (69%) for both HF and LF rTMS with THI 40 (64%) for both HF and LF rTMS with Loudness 40 (64%) for both HF and LF rTMS with Annoyance 38 (61%) for both HF and LF rTMS with Awareness |
| Lorenz I, et al. (2010) | 10 (21–70) | 5 B 4 L 1 R |
No | [LF]-[HF] 1 day of either 1 Hz, IAF (20 trains with 25s ITI), iTBS (10 trains with 8s ITI), or cTBS = 1000 pulses/day @110 %RMT for 1 Hz/IAF or 80% RMT for iTBS/cTBS [D] |
AC contralateral to tinnitus site based on 10–20 EEG system | No | Coil positioned 45° from the skull | Aggravation of tinnitus with IAF (n = 3) | MEG VAS |
NR 1 Hz, iTBS, and cTBS all showed a reduction in tinnitus, while IAF caused an increase in tinnitus. |
| Marcondes RA, et al. (2010) | 10 (>18) | NR | No | [LF] 5 days of (1 Hz × 17min) = 1020 pulses/day @110% MT [T] |
LTC based on 10– 20 EEG system | No | Sham Coil | None | THI VAS SPECT |
NR Significant reduction in tinnitus with Active stimulation versus Sham. Reduction in cortical activity shown by SPECT with Active stimulation. |
| Minami SB, et al. (2010) | 16 (23–79) | 4 B 7 L 5 R |
NR | [LF] 1 day of (1 Hz × 20 mins) = 1200 pulses/day @ 110% RMT [T] |
LAC based on 10–20 EEG system | No | None | None | VAS THI |
NR Significant reduction in VAS scores, but not in THI scores. |
| Vanneste S, et al. (2010) | 100 (38–63) | 25 B 23 U 52 NR |
NR | [LF]-[HF] 1 day of (1, 5, 10, 20 Hz w/5 pulse bursts) = 800 pulses/day @ 90%MT [D]-[T] |
AC, method of locating NR | No | Coil positioned 45° from the skull | NR | VAS TQ |
48(48%) 48 patients were described as placebo free responders. |
| Mennemeir M, et al. (2011) | 21 (28–75) | 21 B | No | [LF] 5 days of (1 Hz × 30 mins) =1800 pulses/day @ 110%MT [D]-[T] |
MRI-guided using PET asymmetry, posterior one third of the STG that lies opposite to ear with tinnitus if no asymmetry but lateralized tinnitus, or left hemisphere STG if no asymmetry/later alized tinnitus | Yes | Sham Coil w/electrical scalp stimulation | NR Only looked at results of neuropsychological tests as a reporter of detrimental effects. |
VARL PET |
9(43%) |
| Piccirillo JF, et al. (2011) | 14 (42–59) | 9 B 3 R 2 L |
Yes Maintained medication with no change in dose (antidepressant) |
[LF] 10 days of (6 trains of (1 Hz × 5.5 minutes for 5 trains and 6 minutes for last train w/90s ITI)) = 2000 pulses/day @ 110%MT [D]-[T] |
TPJ based on 10– 20 EEG system or neuronavigation | Yes | Sham Coil | Jaw twitch (6) Neck/Shoulder Twitch (5) Facial twitch (4) Headache (2) Eye twitching (1) Facial tingling (1) Jaw pain (1) Arm twitch (1) Lightheadedness (1) Temple pain (1) Aggravation of tinnitus (2) |
THI BDI-II BSI-18 |
2(14%) |
| Vanneste S, et al. (2011) | 78 (22–81) | 55 B 25 U |
NR | [LF]-[HF] 1 day of (1, 3, 5, 10, 20 Hz w/200 pulses per frequency) =1000 pulses/day @ 50%MO [D]-[T] |
Medial frontal cortex defined as 1.5cm anterior to one-third distance from nasion inion. | No | Coil positioned 45° from the skull | NR | VAS | 31(59.61%) 52 out of 78 patients (66.67%) were non responders to sham and were used to calculate the percent of responders/non-responders. |