Table 2.
Characteristics of Accelerated Theta Burst Stimulation in Depression Studies
| Study | Study Design | Acceleration schedule | Patient Sample Accelerated iTBS |
Patient Sample Once-daily rTMS or Sham TBS |
TBS Parameters | Main diagnosis | Treatment outcome measure | Treatment response rates | Comments | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N | Age | F/M | N | Age | F/M | Stimulation site (Localisation method) | % MT | TBS type (no. of pulses/ session) | Total pulses | Inter-session interval (mins) | |||||||
| Duprat et al. (2016)79 | Randomized sham-controlled crossover | 5 sessions/day × 4 days | 50 | 42 | 35/15 | Same patient sample crossed over | L-DLPFC (Neuronav) |
110 | iTBS (1620) |
32,400 | 15 | Treatment-resistant MDD | HDRS | 18/47 (38%) | Rates of response = 38% and remission = 30%. aiTBS found to be safe. Studies that reported on same patient sample: Desmyter et al. 2016;91 Baeken et al. 2017;90 Baeken et al. 2019;148 Caeyenberghs et al. 2019;105 Klooster et al. 2019;103 Baeken et al. 2020;102 Baeken et al. 2020;106 Klooster et al. 2020;107 Wu et al. 2022;104 Wu et al. 2022.108 |
||
| Williams et al. (2018)80 | Open label | 10 sessions/day × 5 days | 6 | 56 | 4/2 | n/a |
L-DLPFC (Neuronav) |
90 | iTBS (1800) | 90,000 | 50 | Treatment-resistant MDD | HDRS | Response = 5/6 (83.3%), Remission = 4/6 (66.7%) |
Initial open-label trial of SNT protocol. | ||
| Brocker et al. (2019)93 | Open label | 8 treatment days Day 1: 1/day Day 2–3: 2/day Day 4–8: 3/day |
9 | 40.67 | 7/2 | n/a |
L-DLPFC (5.5cm) | 80 | iTBS (1782) | 35,640 | 20 | Treatment-resistant MDD and BPAD | CES-D | 5/9 (56%) | Open-label case series. | ||
| Cole et al. (2020)110 | Open label | 10 sessions/day × 5 days | 22 | 44.86 | 12/10 | n/a |
L-DLPFC (Neuronav) |
90 | iTBS (1800) | 90,000 | 50 | Treatment-resistant MDD | MADRS | 90.48% | SNT protocol, with MRI-guided targeting, was well tolerated and safe. | ||
| Fitzgerald et al. (2020)4 | Open label prospective | 3 sessions/day Week 1: 3 days Week 2: 2 days Week 3 and 4: 1 day |
36 | 44 | 19/17 | 38 | 45 | 17/21 | L-DLPFC (Beam F3) | 120 | iTBS (600) | 12,600 | 15 | Treatment-resistant MDD | MADRS | aiTBS (week 4) = 27.8% 10 Hz rTMS (week 4) = 26.3% |
First parallel group comparison between intensive iTBS vs daily 10 Hz rTMS. Similar therapeutic benefits were found. |
| Konstantinou et al. (2020)91 | Case report | 8 sessions/day × 5 days then tapering regime | 1 | 66 | F | n/a | n/a | n/a | (Beam F3) | 110 | iTBS (1800) | 72,000 | Not specified | Treatment-resistant MDD | PHQ-9 BDI |
Achieved depression remission (PHQ-9 = 3, BDI = 18) | Case report of aiTBS in late-life depression in place of ECT during Covid-19 Pandemic. |
| Blumberger et al. (2021)52 | Randomized double-blind and sham-controlled | 2 sessions (iTBS 600)/day OR 1 session (iTBS 1200)/day over 30 days |
103 | 41 | 68/35 | 105 | 42 | 63/42 | L-DLPFC (Neuronav) | 120 | iTBS (600 OR 1200) | 36,000 | 60 (iTBS600) OR 0 (iTBS1200 |
Treatment-resistant MDD | HDRS |
Day 30 Twice-daily iTBS 600 = 44.3% Once-daily iTBS 1200 = 41.1% |
No difference in depression outcomes between once daily iTBS 1200 (no ISI) vs twice daily iTBS 600 (60-min ISI) after 6 weeks. |
| Chen et al. (2021)94 | Randomized, single blind | Accelerated bilateral TBS = 20 sessions, 2–3 sessions/day over 10 days. L-DLPFC 10 Hz rTMS = 20 sessions, 1 session/day over 26 days. |
211 | 80% RMT: 48.2, 120% RMT: 49.1 |
80% RMT: 70/33 120% RMT: 73/35 |
84 | 48.67 | 49/35 | Bilateral DLPFC (Beam F3) |
80 OR 120 | Sequential cTBS and iTBS | 60,000 | 15 | MDD or BPAD | QIDS | Overall = 43.7% 80% RMT TBS: 44.1% 120% RMT TBS: 36.8% rTMS: 51.4% |
Largest accelerated bilateral TBS study to date. No difference in outcomes across the three groups. |
| Konstantinou et al. (2021)92 | Case report | 8 sessions/day × 5 days then tapering regime | 1 | 44 | F | n/a | n/a | n/a | (Beam F3) | 110 | iTBS (1800) | 72,000 | Not specified | Treatment-resistant MDD | PHQ-9 BDI |
Achieved depression response, remission and resolution of psychotic symptoms. | Case report of aiTBS in depression with psychotic features (nihilistic delusions). |
| Cole et al. (2022)109 | Randomized, double-blind and sham-controlled | 10 sessions/day × 5 days | 14 | 49 | 5/9 | 15 | 52 | 5/10 | L-DLPFC (Neuronav) |
90 | iTBS (1800) | 90,000 | 50 | Treatment-resistant MDD | MADRS | Active = 12/14 (85.7%) Sham = 4/15 (26.7%) |
Active SNT protocol was more effective than sham stimulation. |
ACC, Anterior cingulate cortex; Beam F3, F3 stimulation localization using the 10/20 EEG coordination system (as described,” by Beam W, Brockardt JJ, Reeves ST, George MS. An efficient and accurate new method for locating the F3 position for prefrontal TMS applications Brain Stimul 2009;2:50–4); aiTBS, accelerated intermittent theta burst stimulation; BPAD, bipolar affective disorder; BSI, Beck Scale for Suicidal Ideation; BDI, Beck Depression Inventory; cTBS, continuous theta burst stimulation; CES-D, Center for Epidemiological Studies–Depression Rating Scale; DLPFC, dorsolateral prefrontal cortex; ECT, electroconvulsive therapy;EEG, electroencephalogram; HDRS, 17-item Hamilton Depression Rating Scale; Hz, Hertz; ISI, intersession interval; iTBS, intermittent theta burst stimulation; L-DLPFC, left dorsolateral prefrontal cortex; MADRS, Montgomery Åsberg Depression Rating Scale; MDD = major depressive disorder; MRI, magnetic resonance imaging; MT, motor threshold; n/a, not applicable; Neuronav, stimulation localization using neuronavigation technique; QIDS, Quick inventory of depressive symptomatology; PHQ-9, Patient Health Quiestionnaire-9; RMT, resting motor threshold; sgACC, subgenual anterior cingulate cortex; SNT, Stanford Neuromodulation Therapy; TBS, theta burst stimulation; rTMS, repetitive transcranial magnetic stimulation; VMPFC, ventromedial prefrontal cortex.