Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis
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Abstract Patients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I 2 = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I 2 = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.
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Evidence has demonstrated that TBS produces similar antidepressant effects to other forms of neuromodulation therapies including rTMS.
“Evidence has demonstrated that TBS produces similar antidepressant effects to other forms of neuromodulation therapies including rTMS; however, the neurocognitive effects of TBS are less well understood.”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Voigt et al., 2021
The Results (Clinical outcomes) found no statistically significant difference in antidepressant response between TBS and active rTMS, and the Discussion describes comparable response and remission outcomes. The comparison was with standard high-frequency left rTMS in patients with major depressive disorder; the paper does not establish similar effects across other types of neuromodulation therapy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOther reviews have suggested TBS is an effective treatment for reducing mood symptoms among individuals experiencing TRD.
“while other reviews have suggested TBS is an effective treatment for reducing mood symptoms among individuals experiencing TRD (Voigt et al., 2021)”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Voigt et al., 2021
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Intermittent Theta-Burst Stimulation and Depressive Symptoms in Major Depressive Disorder
Ørbo, M. C., Grønli, O., Brochs, M. S., Friborg, O., Vangberg, T. R., Selaas, R., Larsen, C., Mittner, M., Turi, Z., Csifcsák, G., et al. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.21262
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- Authors
- Voigt, J. D., Leuchter, A. F., & Carpenter, L. L.
- Affiliations
- University of California, Los Angeles (US)
- Brown University (US)
- Corresponding author
- Voigt, Jeffrey D.
- Venue
- Translational Psychiatry
- Published
- 2021-05-28
- Volume
- 11
- Issue
- 1
- Pages
- 330-330
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC8163818
- OpenAlex
- W3165230137
- Cited by
- 78
- References
- 23
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 16 · 2023: 19 · 2022: 15 · 2021: 2
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- 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, major depressive disorder, repetitive transcranial magnetic stimulation, treatment-resistant depression, non-inferiority, dorsolateral prefrontal cortex, Hamilton Depression Rating Scale, adverse events
- MeSH terms
- Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Humans, Randomized Controlled Trials as Topic, Treatment Outcome, Prefrontal Cortex, Transcranial Magnetic Stimulation, Depressive Disorder, Treatment-Resistant
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