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.
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.
Publication link: Effectiveness-of-theta-burst-versus-high-frequency-repetitive-transcranial-magnetic-stimulation-in-patients-with-depression-THREE-D-a-randomised-non-inferiority-trial.pdf (researchgate.net)
Study protocols (UK&EU/US/Canada only)
(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
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