Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study
Abstract
Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally,…
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One of the most prevalent and widely known iTBS treatment protocols is based on a study by Li et al and delivers 1800 pulses of iTBS per day for 10 days.
“One of the most prevalent and widely known iTBS treatment protocols is based on a study by Li et al [58] and delivers 1800 pulses of iTBS per day for 10 days.”
This amount of iTBS stimulation appears to be well tolerated and shows a good effect on depressive symptoms, even in a treatment-refractory group.
“This amount of stimulation appears to be well tolerated and shows a good effect on depressive symptoms, even in a treatment-refractory group [58].”
iTBS can be administered in 3 to 10 minutes, compared to the standard 37.5-minute protocol for first-generation TMS.
“Using this approach, iTBS can be administered in 3 to 10 minutes, compared to the standard 37.5-minute protocol for first-generation TMS [58].”
Attrition rates are expected to be low, under 10%, based on similar studies of iTBS protocols for patients with depression and PTSD receiving treatment of similar duration.
“On the basis of similar studies of iTBS protocols for patients with depression and PTSD, receiving treatment of similar duration, attrition rates are expected to be low—under 10% [58,90,91].”
Bilateral TBS protocols studied in major depressive disorder yield higher remission rates than sham TBS while still reducing session duration.
“Bilateral TBS protocols have also been studied in major depressive disorder, and they yield higher remission rates than sham TBS12 while still reducing session duration.”
Prior research has indicated that the sequential bilateral approach involving inhibitory stimulation (1 Hz) to the right DLPFC and excitatory stimulation (10 Hz) to the left DLPFC has exhibited efficacy with standard rTMS and cTBS on the right and iTBS on the left, and has recently demonstrated effectiveness in older individuals.
“Prior research has indicated that the sequential bilateral approach involving inhibitory stimulation (1 Hz) to the right DLPFC and excitatory stimulation (10 Hz) to the left DLPFC has exhibited efficacy with standard rTMS18,19 and continuous theta-burst stimulation (cTBS) on the right and iTBS on the left,20 and has recently demonstrated effectiveness in older individuals.21”
From Can Intermittent Theta-Burst Stimulation of Dorsolateral Prefrontal Cortex Relieve Executive Dysfunction in Patients With Late-Life Depression? (2024) · cites this paper as [20]
There is no current consensus on the optimal intensity for TBS, and other studies have used lower intensities.
“While this intensity is consistent with current recommendations for standard rTMS,5 there is no current consensus on the optimal intensity for TBS and other studies have used lower intensities.12”
The present study used bilateral stimulation rather than unilateral stimulation based on data suggesting better response to bilateral stimulation compared with sham in older adults and data demonstrating efficacy of bilateral cTBS/iTBS compared with sham in adults.
“The present study used bilateral stimulation, rather than the unilateral stimulation in the THREE-D trial, based on data suggesting better response to bilateral stimulation compared with sham in older adults7 and data demonstrating efficacy of bilateral cTBS/iTBS compared with sham in adults.12,36”
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- Authors
- Li, C.-T., Chen, M.-H., Juan, C.-H., Huang, H.-H., Chen, L.-F., Hsieh, J.-C., Tu, P.-C., Bai, Y.-M., Tsai, S.-J., Lee, Y.-C., & Su, T.-P.
- Affiliations
- Taipei Veterans General Hospital (TW)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-05-10
- Volume
- 137
- Issue
- 7
- Pages
- 2088-2098
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2108289758
- Cited by
- 328
- References
- 4
- Citations by year
- 2026: 29 · 2025: 30 · 2024: 31 · 2023: 52 · 2022: 38 · 2021: 40 · 2020: 26 · 2019: 21 · 2018: 19 · 2017: 17 · 2016: 14 · 2015: 3 · 2014: 8
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- theta burst stimulation, treatment-resistant depression, major depressive disorder, intermittent theta burst stimulation, continuous theta burst stimulation, prefrontal cortex, antidepressant efficacy, placebo effect, treatment response prediction, repetitive transcranial magnetic stimulation
- MeSH terms
- Adult, Aged, Analysis of Variance, Antidepressive Agents, Depression, Double-Blind Method, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychiatric Status Rating Scales, Theta Rhythm, Treatment Outcome, Transcranial Magnetic Stimulation, Young Adult
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