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Peer-reviewedCC BY 4.0CNS Spectrums

Clinical outcomes following five-day accelerated intermittent theta burst stimulation for treatment-resistant depression in routine clinical practice: A prospective naturalistic cohort study

  • Asmi Khanna1,2
  • Adrian Espiritu1
  • Lynn Zhu2
  • Mervin Blair3
  • Olivia Giovannetti2
  • Amanda Abate2
  • Janice Knight2
  • Luisa Deutsch2
  • Robyn Waxman1,2
  • Amer M. Burhan2,4
4 affiliations
  1. 1Department of Human Biology, Faculty of Arts & Science, University of Toronto, Toronto, Ontario, Canada
  2. 2Ontario Shores Centre for Mental Health Sciences, Whitby, Ontario, Canada
  3. 3Lawson Health Research Institute, London, ON, Canada
  4. 4Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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Abstract

Objectives: Treatment-resistant depression (TRD) is a debilitating condition occurring in major depressive disorder (MDD) and bipolar II disorder (BP-II). Intermittent theta burst stimulation (iTBS) is an established neuromodulation approach for TRD, but standard delivery requires once-daily sessions over several weeks. Accelerated iTBS (aiTBS) may reduce treatment burden by temporally compressing delivery. We evaluated the implementation, tolerability, and clinical outcomes associated with a 5-day aiTBS schedule for adults experiencing TRD in MDD and BP-II.

Methods: In this single-center, open-label, uncontrolled, prospective naturalistic cohort study, adults with MDD or BP-II experiencing TRD received 30 iTBS sessions (600 pulses/session; total 18 000 pulses) over 5 days with 50-minute inter-session intervals. HAMD-17 was assessed at baseline, post-treatment, and 2-month follow-up. Secondary outcomes included Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), baseline Clinical Global Impression-Severity (CGI-S), post-treatment/follow-up CGI-I, response/remission rates, and adverse events. Longitudinal changes were evaluated using linear mixed-effects models.

Results: Forty-six participants contributed longitudinal data (mean age 44.3 years; 54.4% male). HAMD-17 response rates were 28.3% (n = 13) post-treatment and 37.0% (n = 17) at follow-up; remission rates were 26.1% (n = 12) and 32.6% (n = 15), respectively. Improvements were also observed on PHQ-9 and GAD-7. On CGI-I, 52.2% were rated improved post-treatment and 60.9% at follow-up. The most common adverse event was transient, non-serious stimulation-site pain.

Conclusions: The 5-day aiTBS schedule was logistically feasible, well-tolerated, and associated with reductions in depressive and anxiety symptom scores in a real-world TRD cohort. Randomized sham-controlled trials are needed to confirm these findings.

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Cite

BibTeXRIS
BibTeX
@article{khanna2026clinical,
  title = {{Clinical outcomes following five-day accelerated intermittent theta burst stimulation for treatment-resistant depression in routine clinical practice: A prospective naturalistic cohort study}},
  author = {Asmi Khanna and Adrian Espiritu and Lynn Zhu and Mervin Blair and Olivia Giovannetti and Amanda Abate and Janice Knight and Luisa Deutsch and Robyn Waxman and Amer M. Burhan},
  journal = {CNS Spectrums},
  year = {2026},
  month = oct,
  doi = {10.1017/s1092852926101205},
  url = {https://doi.org/10.1017/s1092852926101205},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Clinical outcomes following five-day accelerated intermittent theta burst stimulation for treatment-resistant depression in routine clinical practice: A prospective naturalistic cohort study
AU  - Asmi Khanna
AU  - Adrian Espiritu
AU  - Lynn Zhu
AU  - Mervin Blair
AU  - Olivia Giovannetti
AU  - Amanda Abate
AU  - Janice Knight
AU  - Luisa Deutsch
AU  - Robyn Waxman
AU  - Amer M. Burhan
PY  - 2026
DA  - 2026/10/15
JO  - CNS Spectrums
DO  - 10.1017/s1092852926101205
UR  - https://doi.org/10.1017/s1092852926101205
AB  - Objectives: Treatment-resistant depression (TRD) is a debilitating condition occurring in major depressive disorder (MDD) and bipolar II disorder (BP-II). Intermittent theta burst stimulation (iTBS) is an established neuromodulation approach for TRD, but standard delivery requires once-daily sessions over several weeks. Accelerated iTBS (aiTBS) may reduce treatment burden by temporally compressing delivery. We evaluated the implementation, tolerability, and clinical outcomes associated with a 5-day aiTBS schedule for adults experiencing TRD in MDD and BP-II.  Methods: In this single-center, open-label, uncontrolled, prospective naturalistic cohort study, adults with MDD or BP-II experiencing TRD received 30 iTBS sessions (600 pulses/session; total 18 000 pulses) over 5 days with 50-minute inter-session intervals. HAMD-17 was assessed at baseline, post-treatment, and 2-month follow-up. Secondary outcomes included Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), baseline Clinical Global Impression-Severity (CGI-S), post-treatment/follow-up CGI-I, response/remission rates, and adverse events. Longitudinal changes were evaluated using linear mixed-effects models.  Results: Forty-six participants contributed longitudinal data (mean age 44.3 years; 54.4% male). HAMD-17 response rates were 28.3% (n = 13) post-treatment and 37.0% (n = 17) at follow-up; remission rates were 26.1% (n = 12) and 32.6% (n = 15), respectively. Improvements were also observed on PHQ-9 and GAD-7. On CGI-I, 52.2% were rated improved post-treatment and 60.9% at follow-up. The most common adverse event was transient, non-serious stimulation-site pain.  Conclusions: The 5-day aiTBS schedule was logistically feasible, well-tolerated, and associated with reductions in depressive and anxiety symptom scores in a real-world TRD cohort. Randomized sham-controlled trials are needed to confirm these findings.
SN  - 1092-8529
SN  - 2165-6509
ER  -