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Intermittent theta burst stimulation (iTBS) versus standard 10Hz repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD)

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.


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 (



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

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