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Theta Burst Stimulation - Daniel Blumberger, M.D. Lecture Recap - 2017 Annual Meeting

By Jay Fleming, MD

Theta Burst stimulation was the focus of a presentation at the 2017 Clinical TMS Society Annual Meeting. Before summarizing the presentation, I wish to first tackle some basic definitions.

What are theta waves?

EEG waves occurring in the brain at a frequency of 4 to 8 Hz (4 to 8 waves per second) are termed theta waves. 

What is Theta Burst TMS (TBS) and how does it differ from rTMS?

Most clinicians are familiar with TMS waves of a regular repetitive frequency. Whether the waves are slow, such a 1Hz (1 pulse per second), or fast 10 to 20Hz (10 to 20 pulses per second), the spacing between pulses is the same: the waves are regular. 

By contrast, Theta Burst waves are patterned rather than regular. One typical example is clusters of 3 waves, each 50 Hz apart, with successive clusters repeated at a certain speed. When such clusters are administered with a frequency of 4 to 8 Hz, i.e. at the theta wave frequency, they are called Theta Burst TMS.  Theta Burst protocols are generally delivered at either the same (120% MT) or lower power (80% MT) and for fewer total pulses with several hundred pulse groups rather than several thousand pulse groups in a treatment session than seen in rTMS. This dramatically shortens the treatment duration to 3 to 6 minutes rather than the 17 to 45 minutes seen with rTMS or dTMS, depending of course on the total number of pulses delivered per treatment.

How does one Modulate Impact of TBS treatment?

When using rTMS, the clinician changes the Hz to achieve different outcomes. Slow (1 Hz) waves are inhibitory and fast (10-20 Hz) waves are activating. How does one achieve modulation using TBS when cluster frequencies are administered only within the 4 to 8 Hz theta rate? TBS can be administered in a variety of patterns: continuously for a time named continuous theta burst (cTBS), in groups of 2 seconds on and 8 seconds off called intermittent theta burst (iTBS), or for extended patterns 5 seconds on, 10 seconds off called intermediate TBS (imTBS).  cTBS has an inhibitory effect, iTBS has a stimulatory effect and imTBS is indeed intermediate in that it has neither inhibitory nor stimulatory impact on the neurons stimulated. Thus while preserving the basic theta wave clusters, one can select a TBS pattern to address the desired outcome.

With this basic introduction, let us summarize the presentation given at the recent meetings.

Dr. Daniel Blumberger, Associate Professor of Psychiatry and Medical Head of the Temerty Centre for Therapeutic Brain Intervention, Toronto, CN presented a literature review of TBS and results from a randomized non-inferiority trial of iTBS to rTMS. This trial is known as the THREE-D study. Non-inferiorty trials are often conducted when an established treatment, in this case rTMS, exists and an experimental form of treatment, in this case iTBS, is not felt to be superior in outcome, nor inferior in outcome to the standard treatment. The study had two hypotheses: first that iTBS would be non-inferior to rTMS in improving depression and second that there would be no difference in tolerability and safety between iTBS and rTMS. The full study recruited 400 patients from throughout Canada with MDD, treated at 3 sites. In the protocols used, both treatments were administered at 120% of MT over the left DLPFC for 20 to 30 sessions. The rTMS was administered 3000 pulses per day at 10 Hz and the iTBS at 600 pulses per day using bursts of 3 at 50 Hz and bursts repeated at 5 Hz for total treatment times of 38 minutes and 3 minutes respectively. An interim analysis after 115 patients showed non-inferiority on both hypotheses. A full analysis is pending but if completed may well establish iTBS as non-inferior to rTMS for MDD, but with much greater treatment speed, resulting in increased clinic capacity and shorter daily patient contact time.