Clinical Support Department of Shenzhen Yingchi Technology Co.,Ltd.

Repetitive transcranial magnetic stimulation (rTMS) was approved by the U.S. Food and Drug Administration (FDA) in 2008 for the treatment of major depression that is refractory to multiple medications. The initial treatment time of rTMS protocol is about 45 minutes, once a day for 20-30 days. This treatment protocol is relatively cumbersome, so new treatment models have emerged, such as theta burst transcranial magnetic stimulation (TBS), which attempts to retain the efficacy of traditional TMS treatment plans while significantly shortening treatment and response times.

1 θ burst transcranial magnetic stimulation

Theta burst stimulation (TBS) is a mixed mode of stimulation, it is a 5Hz cluster stimulation, each cluster can have multiple pulses, pulse stimulation frequency is 50Hz high frequency, 3 pulses are a cluster, continuous repetition frequency of 5Hz cluster stimulation is called cTBS. Intermittent TBS is called iTBS. In clinical studies, TBS has been shown to have a more lasting effect on synaptic plasticity, with a shorter onset of action than rTMS protocols. The unique advantages of TBS allow clinical researchers to compress the total treatment time by increasing the number of stimulations in a short period of time, while potentially providing longer-lasting therapeutic effects.

2 Research

2.1 TBS efficacy verification

In 2018, a THREE-D study demonstrated that iTBS mode can achieve the same efficacy as the standard 10 Hz rTMS protocol in the treatment of patients with treatment-resistant major depression. Compared with the conventional rTMS protocol of 37.5 minutes, the iTBS protocol only takes 3 minutes, significantly shortening the treatment time. This breakthrough allows patients to receive multiple treatments in one day, accelerating the entire treatment process.

On the other hand, for special patients, there are also studies to supplement the above results. Blumberger et al. explored the non-inferiority of bilateral TBS(left iTBS and right cTBS versus bilateral rTMS(left 10Hz and right 1Hz) in elderly patients with depression. The results also showed that TBS was no worse than rTMS in terms of remission rates (35.4% vs. 32.9%, respectively), with similar shedding rates and tolerability.

2.2 Accelerate the clinical application of TBS

Two important studies published earlier this year in the “American Journal of Psychiatry” provided insights into Stanford Neuromodulation Therapy (SNT), an accelerated iTBS mode, Currently approved by the FDA) in geriatric depression and in response to patients re-receiving SNT therapy after relapse.

2.2.1 Effects of SNT on major depression in the elderly

Batail et al. reviewed clinical trial data from Blumberger's team, focusing on patients 60 years and older with treatment-resistant major depressive disorder. They point to several advantages of accelerated iTBS protocols in geriatric depression, including the potential benefits of high doses of TMS on the prefrontal cortex in improving cognition and possibly delaying dementia, and the use of neuronavigation to adjust the intensity according to the distance from the coil to the cortex to minimize the effects of brain atrophy in older patients. In a post hoc analysis, 14 included elderly patients with moderately refractory depression (TRD) showed a strong response to treatment.

2.2.2 Repeated efficacy verification of SNT after relapse of major depressive disorder

Geoly et al. evaluated 27 patients who received SNT after a mean of 26.5 weeks. Twenty-two patients achieved immediate remission after initial treatment, and 20 of them (91%) also reached remission criteria immediately after retreatment, so 74% of patients achieved remission after two treatments. This suggests that the efficacy of retreatment is comparable to that of primary treatment, supporting retreatment as an effective strategy when patients relapse during their initial course of accelerated iTBS.

3 Outlook

It has been 16 years since the original rTMS was approved by the FDA for the treatment of depression, and TBS is a breakthrough development in the field, which significantly reduces the treatment time, can add more pulse stimulation, and has a shorter response time than conventional rTMS protocols.

However, many questions still remain, including persistence, the optimal number of treatments in a day, the number of pulses that can be safely applied, and the advantages of using neuroimaging to identify stimulation targets, which can increase treatment costs and reduce generalization. Clearly, TBS has the potential to improve the status quo in depression treatment, and we need to consider how to promote it and make it more effective.

Statement 

1.This content is organized by the Clinical Support Department of Shenzhen Yingchi Technology Co.,Ltd. Criticisms and corrections are welcome. For reprint, please indicate the source.

2.Reference:

[1]Batail, J. M. V., Feyder, M. T., Bentzley, B. S., & Williams, N. R. (2024). An avenue for optimization of theta burst stimulation protocols? Comments on the FOUR-D randomized noninferiority clinical trial. American Journal of Psychiatry, 181(1), 68-70.
[2]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.
[3]Blumberger, D. M., Mulsant, B. H., Thorpe, K. E., McClintock, S. M., Konstantinou, G. N., Lee, H. H., ... & Downar, J. (2022). Effectiveness of standard sequential bilateral repetitive transcranial magnetic stimulation vs bilateral theta burst stimulation in older adults with depression: the FOUR-D randomized noninferiority clinical trial. JAMA psychiatry, 79(11), 1065-1073.
[4]Chung, S. W., Hoy, K. E., & Fitzgerald, P. B. (2015). Theta‐burst stimulation: A new form of TMS treatment for depression?. Depression and anxiety, 32(3), 182-192.
[5]Geoly, A. D., Kratter, I. H., Toosi, P., Cole, E. J., Sahlem, G. L., & Williams, N. R. (2024). Sustained efficacy of Stanford Neuromodulation Therapy (SNT) in open-label repeated treatment. American Journal of Psychiatry, 181(1), 71-73.
[6]McDonald, W. M. (2024). Theta burst TMS technology: great promise and a lot to learn. American Journal of Psychiatry, 181(1), 14-15.