Theta burst stimulation for depression: a systematic review and network and pairwise meta-analysis
Open accessAbstract
In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression.
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Depression and PTSD-the two domains for which TMS and theta-burst stimulation are most extensively supported-improved significantly at both post-treatment and follow-up.
“Depression and PtsD-the two domains for which tMs and theta-burst stimulation are most extensively supported (Blumberger et al. 2018;cole et al. 2022;Kishi et al. 2024;Petrosino et al. 2020;Philip et al. 2019)-improved significantly at both post-treatment and follow-up.”
From Feasibility, tolerability, and preliminary effectiveness of an accelerated bilateral intermittent theta-burst stimulation protocol in adults with posttraumatic stress disorder and comorbid depressive disorder following mild traumatic brain injury (2026) · cites this paper as Kishi et al. 2024
The Introduction (page unavailable) says rTMS is recommended for treatment-resistant depression and that iTBS is approved for depression; the Results report improved depression outcomes with some TBS protocols. The paper does not address PTSD or compare which clinical domains have the most extensive support. The citation is attached to that background characterization, not to the citing authors’ post-treatment and follow-up results. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe magnitude and direction of effects observed in this study are broadly consistent with effect sizes reported in prior TMS/PTSD and TMS/depression literature.
“the magnitude and direction of effects observed here are broadly consistent with effect sizes reported in prior tMs/PtsD and tMs/depression literature”
From Feasibility, tolerability, and preliminary effectiveness of an accelerated bilateral intermittent theta-burst stimulation protocol in adults with posttraumatic stress disorder and comorbid depressive disorder following mild traumatic brain injury (2026) · cites this paper as Kishi et al. 2024
The Results (Network meta-analysis results; page unavailable) report effect sizes and improvement in depression symptoms for two theta-burst stimulation protocols compared with sham. This supports the depression-literature portion, but the paper does not report PTSD effect sizes or compare its estimates with the citing study’s effects, so the claimed consistency across both literatures is not established. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRepetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder.
“Repetitive transcranial magnetic stimulation (rtMs) is an established treatment for major depressive disorder”
Intermittent theta-burst stimulation (iTBS) is a validated, substantially abbreviated alternative that is noninferior to conventional 10-Hz rTMS for depression.
“intermittent theta-burst stimulation (itBs) is a validated, substantially abbreviated alternative that is noninferior to conventional 10-hz rtMs for depression”
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- Authors
- Kishi, T., Ikuta, T., Sakuma, K., Hatano, M., Matsuda, Y., Wilkening, J., Goya-Maldonado, R., Tik, M., Williams, N. R., Kito, S., & Iwata, N.
- Affiliations
- Fujita Health University (JP)
- University of Mississippi (US)
- Jikei University School of Medicine (JP)
- Universitätsmedizin Göttingen (DE)
- Stanford University (US)
- Corresponding author
- Kishi, Taro
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2024-06-06
- Volume
- 29
- Issue
- 12
- Pages
- 3893-3899
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC11609094
- OpenAlex
- W4399392190
- Cited by
- 74
- References
- 55
- Citations by year
- 2026: 48 · 2025: 23 · 2024: 3
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PUBLISSO (German National Library of Medicine) (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Funders
- Japan Agency for Medical Research and Development (JP22dk0307107, JP22wm0525024)
- 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, depression, major depressive disorder, continuous theta burst stimulation, intermittent theta burst stimulation, repetitive transcranial magnetic stimulation, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, occipital lobe, response rate, remission rate, mania, headache, treatment discontinuation, benefits and risks
- MeSH terms
- Network Meta-Analysis, Dorsolateral Prefrontal Cortex, Adult, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Theta Rhythm, Randomized Controlled Trials as Topic, Treatment Outcome, Transcranial Magnetic Stimulation
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