A pilot investigation of an intensive theta burst stimulation protocol for patients with treatment resistant depression
Open accessAbstract
INTRODUCTION: Accelerated or intensive forms of repetitive transcranial magnetic stimulation (rTMS) are increasingly being explored for their potential to produce more efficient and rapid treatment benefits in major depressive disorder (MDD). However, accelerated or intensive protocols using standard forms of rTMS are still quite time-consuming to apply. Theta burst stimulation (TBS) is a novel form of magnetic stimulation with the potential to produce similar anti-depressant effects but in a much abbreviated period of time. The aim of this study was to investigate the comparative efficacy of an intensive TBS protocol compared to standard rTMS treatment. METHODS: 74 outpatients (36 female, mean age 44.36 ± 12.1 years) with MDD received either intensive TBS (3 intermittent TBS treatments per day for 3 days in week 1, 3 treatments a day for 2 days in week 2, and 3 treatments in 1 day in week 3 and in week 4, or standard rTMS (5 daily sessions per week for 4 weeks). Patients were assessed weekly throughout the treatment course, and at 4 weeks after treatment end. RESULTS: There were no significant differences in the degree of reduction in depressive symptoms, the rate of reduction in depressive symptoms, remission or response rates (response rates = 27.8% for intensive group, 26.3% for the standard group, p > 0.05 for all analyses) between the intensive TBS and standard rTMS treatment groups. However, the overall response and remission rates were limited in both groups. There was no difference in rates of side effects, no serious adverse events and no alterations in cognitive performance. CONCLUSION: Intensively applied TBS appears to have similar efficacy to standard rTMS when these were applied as delivered in this study but does not produce more rapid clinical benefits. The overall response rates in both groups in this study were limited, most likely by the total doses provided in both study arms. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12616000443493.
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Two included studies included a bilateral standard rTMS comparison condition.
“Two studies (Blumberger et al., 2022;Fitzgerald et al., 2020) included a bilateral standard rTMS comparison condition.”
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 Fitzgerald et al., 2020
The study did include a standard rTMS comparison arm (Study design, §2.1), but our copy describes stimulation in that arm as applied to the left side (treatment description reproduced near §4). The Treatment section (§2.4) also identifies the F3 site. This contradicts the claim that this study’s standard rTMS comparison was bilateral; the cited passages provide no page numbers. (LLM, conf=0.84)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredFitzgerald et al. (2020) found no within- or between-group differences in performance on Trail Making Test Part A.
“While Fitzgerald et al. (2020) found no within-or between-group differences in performance”
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 Fitzgerald et al., 2020
Section 3.7 (Cognition; page not provided) reports no between-group differences in cognitive change scores, supporting that part of the claim. But it reports a significant within-group improvement on Trail Making Test Part A in the standard rTMS group (p = 0.01), contrary to the claim of no within-group difference. (LLM, conf=0.92)
Experimental — accuracy not yet measuredFour studies included measures of attention and working memory.
“Four studies (Cole et al., 2020;Cristancho et al., 2023;Fitzgerald et al., 2020;Holczer et al., 2021) included measures of attention and working memory.”
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 Fitzgerald et al., 2020
Fitzgerald et al. (2020) found no significant between-group differences in BVMT-R change scores from baseline to treatment end.
“Fitzgerald et al. (2020) found no significant between group differences in BVMT-R change scores from baseline to treatment end.”
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 Fitzgerald et al., 2020
Fitzgerald et al. (2020) found no between-group differences in RAVLT change scores from baseline to treatment end.
“Using the Rey Auditory Verbal Learning Test (RAVLT), Fitzgerald et al. (2020) found no between group differences in change scores from baseline to treatment end”
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 Fitzgerald et al., 2020
Fitzgerald et al. (2020) found that individuals in the TBS group experienced significantly improved performance on RAVLT recognition.
“however, individuals in the TBS group experienced significantly improved performance on RAVLT recognition.”
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 Fitzgerald et al., 2020
Fitzgerald et al. (2020) reported improvement in Stroop Word reading performance in the TBS group.
“Also, Fitzgerald et al. (2020) reported improvement in Stroop Word reading performance in the TBS group.”
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 Fitzgerald et al., 2020
Some evidence suggested that TBS, independent of its improvement in depression severity, may be associated with improvement in attention, processing speed, aspects of executive function, and verbal recognition.
“and some evidence suggested that TBS, independent of its improvement in depression severity (Cheng et al., 2016;Fitzgerald et al., 2020), may be associated with improvement in attention, processing speed, aspects of executive function, and verbal recognition.”
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 Fitzgerald et al., 2020
Fitzgerald et al. (2020) found no significant within- or between-group differences in change scores from baseline to posttreatment on the WMS-III Digit Span subtest measuring auditory attention and working memory.
“Fitzgerald et al. (2020) measured auditory attention and working memory using the Wechsler Memory Scale-3rd Edition (WMS-III) Digit Span subtest and found no significant within-or between-group differences in the change scores from baseline to posttreatment.”
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 Fitzgerald et al., 2020
There were findings of neurocognitive enhancement in processing speed (Fitzgerald et al., 2020).
“processing speed (Fitzgerald et al., 2020)”
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 Fitzgerald et al., 2020
There were findings of neurocognitive enhancement in verbal learning (Fitzgerald et al., 2020).
“and verbal learning (Fitzgerald et al., 2020).”
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 Fitzgerald et al., 2020
Two studies included the Trail Making Test Part A.
“Two studies (Fitzgerald et al., 2020;Scho et al., 2019) included Trail Making Test (TMT) Part A.”
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 Fitzgerald et al., 2020
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Cites
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“[18] and the Clinical Global Impression Severity and Improvement scales (CGI-S).”
An efficient and accurate new method for locating the F3 position for prefrontal TMS applications
Beam, W., Borckardt, J. J., Reeves, S. T., & George, M. S. (2009) · Brain Stimulation · doi:10.1016/j.brs.2008.09.006 · Cited by 626 · see citing works
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- Authors
- Fitzgerald, P. B., Chen, L., Richardson, K., Daskalakis, Z. J., & Hoy, K. E.
- Affiliations
- Epworth Hospital (AU)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Fitzgerald, Paul B.
- Venue
- Brain Stimulation
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 13
- Issue
- 1
- Pages
- 137-144
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- OpenAlex
- W2969425970
- Cited by
- 87
- References
- 6
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 14 · 2023: 14 · 2022: 12 · 2021: 13 · 2020: 8 · 2019: 1
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain stimulation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Health and Medical Research Council (1078567, 1082894)
- Campbell Institute (1041890)
- Centre for Addiction and Mental Health
- Brain and Behavior Research Foundation
- Canadian Institutes of Health Research
- 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, repetitive transcranial magnetic stimulation, treatment-resistant depression, major depressive disorder, antidepressant efficacy, adverse effects, cognitive performance
- MeSH terms
- Adult, Female, Humans, Male, Middle Aged, Theta Rhythm, Transcranial Magnetic Stimulation, Depressive Disorder, Treatment-Resistant
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