Table 1. Literature review summary of auditory hallucinations (AH) treatment or investigation by rTMS.
All studies used a Figure of 8 TMS coil except for Loo et al (2009), which used a circular coil and Rosenberg et al (2011), which used an H-coil. AC, auditory cortex; AH, auditory hallucinations; AHRS, auditory hallucination rating scale; AVH, auditory visual hallucinations; BPRS, 18-item brief psychiatric rating scale; CGI, clinical global impression scale; cTBS, continuous theta burst (3 50Hz pulses at 5Hz); D, diagnostic; DVR, daily voices ratings questionnaire; fMRI, functional magnetic resonance imaging; HCS, hallucination change scale; ITI, intertrain interval; LORETA, low-resolution brain electromagnetic tomography; LTC, left tempoparietal cortex; MRI; magnetic resonance imaging; MT, motor threshold; NR, not reported; PANAS, positive and negative affect scale; PANNS (H), positive and negative syndrome scale hallucinations subscale; PET, positron emission tomography; PSYRATS (AH), pyschotic symptom ratings scale auditory hallucinations subscale; QLS, quality of life scale; RMT, resting motor threshold; SPECT, single photon emission computed tomography; STG, superior temporal gyrus; RTC, right tempoparietal cortex; rTMS, repetitive transcranial magnetic stimulation; SAH, scale for assessment of auditory hallucinations; SANS, scale for assessment of negative symptoms; SAPS, scale for assessment of positive symptoms; t, therapeutic; TPJ, tempo-parietal junction; VAS, analog scale of auditory hallucinations
| Author (Year) | # of Subjects (Age Range) | Drug Therapy details | rTMS Protocol [Therapeutic or Diagnostic] | Coil Position | MRI Navigation | Sham Method | Adverse Events details | AH Outcome Measure | # Responders (% total) comments |
|---|---|---|---|---|---|---|---|---|---|
| Hoffman RE, et al. (1999) | 3 (30–54) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 4 days/week × 2 weeks of (1 Hz × 4min (Day 1), 8min (Day 2), 12min (Day 3), 16min (Day 4)) = 240–960 pulses/day @ 80% MT [T] |
Halfway between T3 and P3 based on 10– 20 EEG system | No | Coil tilted 45° from the skull | None | Individualized composite score | 3 (100%) |
| Hoffman RE, et al. (2000) | 12 (32–50) | Yes Maintained medication with no change in dose (anticonvulsant, antipsychotic) |
[LF] 4 days/week × 2 weeks of (1 Hz × 4min (Day 1), 8min (Day 2), 12min (Day 3), 16min (Day 4)) = 240–960 pulses/day @ 80% MT [T] |
Halfway between T3 and P3 based on 10–20 EEG system | No | Coil tilted 45° from the skull | Headache (n = 2) | Individualized composite score | NR Symptom improvements relative to baseline were significant for 12 and 16min stimulation. |
| d’Alfonso AA, et al. (2002) | 9 (19–43) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 8 days of (1 Hzx 20min) = 1800 pulses/day @ 80% MT [T] |
2cm above T3 based on 10–20 EEG system | No | None | NR | Topography of Voices Rating Scale | NR Statistically significant effect on hallucination severity ratings. 7 out of 8 patients had severity improvement at week 2. |
| Schreiber S, et al. (2002) | 1 (49) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 5 days/week × 4 weeks of (20 trains (10 Hz × 6s (w/1 min ITI))) = 1200 pulses/day @ 90% MT [T] |
RDLPFC chosen using documentation of right hypofrontality in pre-treatment SPECT | No | None | NR | VAS BPRS PANSS SPECT |
0 (0%) |
| Hoffman RE, et al. (2003) | 21 (18–60) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 9 days of (1 Hz × 8min (Day 1), 12min (Day 2), 16min (Day 3–9)) = 480–960 pulses/day @ 90% MT [T] |
LTC based on 10–20 EEG system | No | Coil tilted 45° from the skull | Headache (n = 6) Lightheaded (n = 4) Concentration difficulty (n = 3) Memory difficulty (n = 1) Aggravation of AH (n = 3) Racing thoughts (n = 1) Visual hallucination (n = 1) Ischemic chest pain (n = 1) Chest pain caused by factors such as smoking, diabetes, and hypertension. |
AHRS | 9 (75%) |
| Schonefeldt- Lecuona C, et al. (2004) | 11 (26–58) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 5 days of (1 Hz × 16 min) =960 pulses/day @ 90% MT [T] |
LSTG and Broca’s area based on fMRI | Yes | Coil placed over the parieto-occipital transition | Stimulation over the temporal muscle when targeting superior temporal gyrus or Broca’s area was generally reported as uncomfortable. | Haddock self-rating scale | 3(27%) |
| Lee SH, et al. (2004) | 25 (18–60) | NR | [LF] 8 days of (1 Hz × 20min) = 1200 pulses/day @ 100% MT [T] |
LTC or RTC based on 10–20 EEG system | No | Coil perpendicular to head | Headache (n = 5) Dizziness (n = 2) Amnesia (n = 1) |
AHRS | NR Significant improvements in frequency of AHs, positive symptoms of PANSS, and CGI-I scores. |
| McIntosh AM, et al. (2004) | 16 (22–65) | NR | [LF] 4 days/week × 2 weeks of (1 Hz × 4min (Day 1), 8min (Day 2), 12min (Day 3), 16min (Day 4)) w/15s interval between each minute of stimulation = 240–960 pulses/day @ 80% MT [T] |
LTC based on 10–20 EEG system | No | Coil tilted 45° from the skull | Many patients complained of headache during active treatment. | VAS | NR No significant effects of TMS on symptom measures were found. |
| Chibbaro G, et al. (2005) | 8 (21–53) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 4 days out of 8 weeks of (1 Hz × 15min) = 900 pulses/day @ 90% MT [T] |
LTC based on 10–20 EEG system | No | Coil tilted 45° from the skull | NR | SAPS SANS SAH |
NR Significant improvement in SAPS, SANS, and SAH scores for real rTMS versus sham. |
| Fitzgerald PB, et al. (2005) | 17 (16–65) | Yes Maintained medication with no change in dose (antidepressant, antipsychotic) |
[LF] 8 days of (1 Hz × 15min) w/30s break at halfway point = 900 pulses/day @ 90% MT [T] |
TP3 marking based on 10–20 EEG system | No | Coil tilted 45° from the skull | None | PSYRATS (AH) PANNS (H) |
NR No clinically significant reduction in loudness of voices. |
| Hoffman RE, et al. (2005) | 27 (18–60) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 9 days of (1 Hz × 8min (Day 1), 12min (Day 2), 16min (Day 3–9)) = 480–960 pulses/day @ 90% MT [T] |
Halfway between T3 and P3 based on 10– 20 EEG system | No | Coil tilted45° from the skull | Memory difficulty (n = 2) Headache, lightheadedness, and concentration difficulty all reported. |
HCS AHRS PANNS (H) |
14 (51.9%) |
| Poulet E, et al. (2005) | 10 (25–51) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 15 days of (1 Hz × 33min) = 2000 pulses/day @ 90% MT) [T] |
Halfway between T3 and P3 based on 10– 20 EEG system | No | Sham Coil | Headache (n = 1) | AHRS | 7 (70%) 7 responders at 1-month follow-up; 5 (50%) at 2 month follow-up |
| Fitzgerald PB, et al. (2006) | 2 (18–47) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 10 days of (1 Hz × 15min) = 900 pulses/day @ 90% RMT [T] |
TP3 marking based on 10–20 EEG system | No | None | NR | HCS PANSS |
2(100%) |
| Jandl M, et al. (2006) | 16 (19–70) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 15 days of (1 Hz × 15min) = 900 pulses/day @ 100% MT [T] |
Left posterior portion of STG, right posterior portion of STG, and midway based on to 10–20 EEG setup | No | Coil midway T4-P4 | Headache (n = 1) Clicking noise persistence (n = 1) |
PSYRATS (AH) | 6 (38%) 5 (31%) with right hemisphere stimulation; 1 (6%) with left hemisphere stimulation |
| Langguth B, et al. (2006) | 1 (25) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 20 days of (1 Hz × 33min) = 2000 pulses/day @ 110% MT [T] |
LTC based on PET/MRI | Yes | None | NR | AHRS | 1 (100%) |
| Poulet E, et al. (2006) | 1 (50) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 10 days of (1 Hz × 16.6min) =1000 pulses/day @ 100% MT followed by: Maintenance with 1 day of (1 Hz × 16.6 min) = 1000 pulses/day @ 100% MT [T] |
Halfway between T3 and P3 based on 10– 20 EEG system | No | None | NR | AHRS SAPS |
1(100%) |
| Favalli G, et al. (2007) | 1 (59) | NR | [LF] 20 days of (1Hz × 20min) = 1200 pulses/day @ 90% MT [T] |
Halfway between T3 and P3 based on 10– 20 EEG system | No | None | NR | AHS BPRS |
1(100%) |
| Fitzgerald PB, et al. (2007) | 3 (23–61) | Yes Maintained medication with no change in dose (anticonvulsant, antipsychotic) |
[LF] 10 days of (1 Hz × 15min) = 900 pulses/day @ 90% RMT [D] |
TP3 marking based on 10–20 EEG system | No | None | NR | PANSS PSYRATS (AH) HCS |
3(100%) |
| Horacek J, et al. (2007) | 12 (25–44) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 10 days of (0.9 Hz × 20min) = 1080 pulses/day @ 100% MT [D] |
LTC based on 10–20 EEG system | No | None | Mild Headache | AHRS HCS PANSS PET LORETA |
NR Significant decrease in Hallucination item and positive PANSS score. |
| Rosa MO, et al. (2007) | 6 (18–50) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 8 days of (1 Hz × 16min) = 960 pulses/day @ 90% MT [T] |
LTC based on 10–20 EEG system | No | Sham Coil | Headache (n = 1) | AHRS VAS |
NR Weak reduction in auditory hallucinations. |
| Sommer IEC, et al. (2007) | 15 (27–45) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 15 days of (1 Hz × 20min) = 1200 pulses/day @ 90% MT) [T] |
Based on fMRI data or halfway between T3 and P3 based on 10–20 EEG system | Yes | None | Increased Anxiety/Suspicion (n = 2 ) | AHRS PANSS |
NR There was a significant decrease in AVH during the study. |
| Thirthalli J, et al. (2008) | 1 (22) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] Sessions of (1 Hz × 15 min) = 900 pulses/day @ 100% MT [T] |
LTC based on 10–20 EEG system | No | None | Headache (n = 1) | PANSS (AH) | 1 (100%) |
| Bagati D, et al. (2009) | 40 (18–37) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 10 days of 1 Hz @ 90% MT [T] |
LTC based on 10–20 EEG system | No | None | NR | AHRS PSYRATS (AH) |
NR Significant reduction of AH parameters of AHRS scores. |
| Garcia-Toro M, et al. (2009) | 1 (26) | Yes Maintained medication with no change in dose (antipsychotic) |
[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) | PSYRATS (AH) | 1 (100%) |
| Montagne- Larmurier A, et al. (2009) | 11 (24–57) | Yes Maintained medication with no change in dose (antipsychotic) |
[HF] 2 days with 2 sessions of 13 trains (20 Hz × 10s (w/50s ITI)) = 5200 pulses/day @ 80% RMT [T] |
STS using fMRI and frameless stereotaxic TMS system | Yes | None | Headache (n=2) Slight contractions of temporal and facial muscles were reported |
AHRS CGI |
7 (63.8%) |
| Vercammen A, et al. (2009) | 24 (19–48) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 6 days with 2 sessions of (1 Hz × 20min) = 2400 pulses/day @ 90% MT [T] |
RTC and LTC based on 10–20 EEG system | No | Sham Coil | Headache (n = 8) Tingling sensation (n = 1) Restless legs (n = 1) Light-headedness (n = 1) Transient earache (n = 1) Twitching of facial muscles (n = 7) |
AHRS PANAS PANSS |
8 (33%) immediately after rTMS; 6 (28.6%) after 1 week |
| Consentino G, et al. (2010) | 1 (63) | NR | [LF] 10 days of (1 Hz × 20min) = 1200pulses/day @ 90% MT [T] |
Right posterior temporal lobe as determined by MRI and PET | Yes | None | NR | Self-rated scale from 1 to 10 | 1(100%) |
| de Jesus DR, et al. (2010) | 8 (18–65) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 20 days of (Day 1 (1 Hz × 8 mins), Day 2 (1 Hz × 16 mins), and Days 3–20 (1 Hz × 20 mins) =480–1200 pulses/day @ 90% MT [T] |
LTC based on 10–20 EEG system | No | Coil tilted 45° from the skull | Headache (n=2) | BPRS QLS CGI AHRS |
NR There was no significant effect observed on AHs. |
| Dollfus S, et al. (2010) | 1 (56) | Yes Maintained medication, however a new regimen was started during treatment(antip sychotic) |
[LF]-[HF] 10 days of (1 Hz × 20min) = 1200pulses/day @ 90% MT 2 days of (2 sessions of 13 trains (20 Hz × 10s)) = 5200 pulses/day @ 80% RMT [T] |
TP3 marking based on 10–20 EEG system or left superior temporal sulcus based on fMRI | Yes | None | None | AHRS | 1(100%) Patient responded with HF stimulation, but not with LF stimulation. |
| Eberle MC, et al. (2010) | 1 (52) | Yes Maintained medication with no change in dose (antipsychotic) |
[HF] 45 days of (40s (3 pulses at 50 Hz every 200 msec)) =600 pulses/day @ 80% AMT [T] |
TP3 and TP4 marking based on 10–20 EEG system | No | None | None | HCS | 1(100%) |
| Hong N, et al. (2010) | 1 (79) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 15 days of (1Hz) [T] |
LTC, but method of locating NR | No | None | Aggravation of AH (n = 1) Persisted for one month after rTMS. |
PSYRATS (AH) | 1(100%) |
| Lai I, et al. (2010) | 8 (34–48) | Yes Maintained medication with no change in dose (antipsychotic) |
[HF] 11 days of (1 Hz × 16 min) = 960 pulses/day @ 90% MT [T] |
LTC, method of location NR | No | Yes, but method not reported | None | CGI HCS |
3 (37.5%) with 50% reduction 2 (25%) with 20% reduction 1 (12.5%) with 10% reduction |
| Loo CK, et al. (2010) | 18 (20–74) | Yes Maintained medication with no change in dose (antidepressant, antipsychotic) |
[LF] 3 days of (1 Hz × 16 min) = 960 pulses/day @ 110% MT [T] |
Posterior half of the LSTG and RSTG based on MRI | Yes | Coil tilted 45° from the skull | Increase in auditory threshold (n = 2) Eight participants reported experiencing side-effects during the active treatment (right or left), with the most commonly reported side- effect being twitching |
AHRS DVR |
5 (27%) |
| Slotema CW, et al. (2010) | 42 (26–51) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 15 days of (1 Hz × 20 mins) = 1200 pulses/day @ 90% MT [T] |
Halfway between T3 and P3 based on 10– 20 EEG system Site of maximal fMRI activation during AVHs |
Yes | Coil tilted 90° from the skull | Facial twitching (n = 7) Increased psychosis (n = 2) Scalp discomfort (n = 1) Headache (n = 9) Nausea (n = 1) Dizziness (n = 1) Abdominal pain (n = 1) Fatigue (n = 1) |
AHRS PSYRATS (AH) HCS PANSS |
rTMS was not able to significantly reduced AVH as compared to sham. |
| Sperling W, et al. (2010) | 1 (37) | No | [LF] 4 days of (1 Hz × 10 min) × 2 hemispheres =1200 pulses/day (600/hemisphere) @ 90% MT [T] |
Halfway between T3 and P3 based on 10– 20 EEG system on Left and Right side | No | None | NR | SAPS | 1 (100%) |
| Subramanian P, et al. (2010) | 1 (24) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 20 days of 1 Hz stimulation =Unknown # of pulses @ 100% RMT [T] |
LTC and RTC based on 10–20 EEG system | No | None | Increased passivity experiences of volition and impulse (n = 1) | VAS | 1 (100%) |
| Vercammen A, et al. (2010) | 9 (21–52) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 6 days of (1 Hz × 20 min) for a total of 12 sessions. =2400 pulses/day @ 90% MT [D] |
Halfway between T3 and P3 based on 10– 20 EEG system | No | Sham Coil | NR | PANSS | NR Left TPJ active stimulation showed significant decrease in PANSS score. |
| Rosenberg O, et al. (2011) | 8 (28–62) | Yes Maintained medication with no change in dose (antipsychotic) |
[LF] 10 or 20 days of (1 Hz × 10 min) =600 pulses/day @ 110% MT [T] |
LTC based on H-coil magnetic field modeling. | No | None | Headache (n = 1) | AHRS SAPS CGI SANS |
7(87.5%) Improvement in both 10 and 20 day treatment regimens. This improvement was less in 20 days, but upon follow-up the reduction in AH was markedly more as compared to 10 days of treatment. |