Publication Reference
Blumberger, D. M., Vila-Rodriguez, F., Thorpe, K. E., Feffer, K., Noda, Y., Giacobbe, P., … & Downar, J. (2018). Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. The Lancet, 391(10131), 1683-1692.
Article Summary*
This study aimed to compare the effectiveness, safety, and tolerability of the standard 10Hz FDA cleared protocol (37-minutes duration) to intermittent theta burst stimulation (iTBS; 3-minutes duration) for treatment-resistant MDD. All participants were unsuitable for or had failed on at least two antidepressant trials within the current depressive episode. Further, any participants who were receiving medication were on a stable dosage for at least 4 weeks prior to study entry and throughout the study duration. Treatment was applied open-label, but treatment outcome assessors were blinded to the treatment conditions. Whilst balancing for depression severity, participants were randomly allocated to receive either 10Hz rTMS (n = 205) or iTBS (n = 209) to the left dorsolateral prefrontal cortex (DLPFC) for 4-6 weeks. In both groups there was an improvement in 17-Item Hamilton Rating Scale for Depression (HRSD-17) scores, from 23.5 to 13.4 in the 10Hz group and from 23.6 to 13.4 in the iTBS group, indicating both treatments were equally effective. On a verbal analogue scale subjective pain at the site of stimulation was slightly higher in the iTBS group versus the 10Hz group (3.8/10 and 3.4/10, respectively; p = 0.011). However, headache was the most common adverse side-effect across both groups with approximately equal occurrence, and dropout rates were comparably low (10Hz = 6%; iTBS = 8%). 12 weeks after treatment, response and remission rates were 47% and 27% in the 10Hz group and 49% and 32% in the iTBS group, respectively. The authors concluded that iTBS led to significant and clinically meaningful response and remission rates that were non-inferior to those achieved by the 10Hz protocol.
*For original abstract/publication see the link below.
Study protocols (UK&EU/US/Canada only)
| Stimulation site | Power (motor threshold %) | Freq | Train duration | No. of pulses | Intertrain interval (wait time) | No. of trains | Total no. of pulses | Approx. session duration |
| Left DLPFC | 120% resting MT | 10Hz
| 4s | 40 | 26s | 75 | 3000 | 37.5 mins |
10Hz protocol parameters
Visual representation of the 10Hz protocol
| Stimulation Site | Protocol | Power (motor threshold %) | Freq | Burst Freq | No. of Pulses | No. of Bursts | Cycle Time | No. of Cycles | Total pulses |
| Left DLPFC | iTBS 600 | 120% resting MT | 50Hz | 5Hz | 3 | 10 | 10s | 20 | 600 |
iTBS protocol parameters
Visual representation of the iTBS protocol