Pragmatic Accelerated Theta-Burst Stimulation Shows Promise for Treatment-Resistant Depression

March 24, 2025

Written by Joao L. de Quevedo, MD, PhD

Introduction

Major depressive disorder (MDD) affects millions worldwide, and for nearly half of these individuals, standard treatments such as medication and psychotherapy are insufficient. This condition, known as treatment-resistant depression (TRD), has prompted researchers to explore alternative therapies. One such innovation is intermittent theta-burst stimulation (iTBS)—a non-invasive brain stimulation technique targeting neural circuits involved in depression.

A new randomized clinical trial published in JAMA Psychiatry examines a more intensive approach: accelerated theta-burst stimulation (aTBS). This study, conducted in São Paulo, Brazil, evaluated whether a practical aTBS protocol could offer a more effective and accessible solution for individuals with TRD.

The Study: Accelerated Theta-Burst Stimulation for TRD

The study, led by Andre R. Brunoni and colleagues, tested a streamlined aTBS protocol on 100 participants diagnosed with TRD. Patients received 45 stimulation sessions over 15 days—three iTBS sessions per day, each spaced 30 minutes apart. The treatment targeted the left dorsolateral prefrontal cortex (DLPFC), an area linked to emotional regulation.

This triple-blinded, sham-controlled clinical trial (meaning neither the patients, raters, nor operators knew the treatment assignments) assessed the effectiveness and safety of this protocol. The primary outcome measured was reduced Hamilton Depression Rating Scale (HDRS-17) scores after five weeks.

Key Findings

  1. Significant Symptom Reduction
    • The active aTBS group saw a 54.7% reduction in depression severity compared to 31.87% in the sham group.
    • The effect size (Cohen’s d = 0.65) was medium to large, indicating a substantial therapeutic benefit.
  2. Higher Response and Remission Rates
    • Response rate (≥50% reduction in HDRS-17 score):
      • Active aTBS: 52%
      • Sham group: 22%
    • Remission rate (HDRS-17 score <8):
      • Active aTBS: 34%
      • Sham group: 16%
  3. Well-Tolerated Treatment with Mild Side Effects
    • The most common side effect was mild scalp pain, reported in 17.4% of active group participants compared to 4.4% in the sham group.
    • No serious adverse effects, including seizures or manic switches, were reported.
  4. Open-Label Phase: Continued Improvement with Additional Sessions
    • Patients who did not initially respond to sham treatment were offered real aTBS sessions.
    • Of those who received extended treatment, 75% showed significant improvement, demonstrating the potential for additional stimulation to enhance recovery.

Why This Matters

Traditional iTBS protocols are time-consuming and often require expensive neuronavigation tools to target brain areas precisely. This study introduces a cost-effective, practical protocol to implement in real-world clinical settings without neuronavigation.

Moreover, the findings support the idea that increasing treatment intensity (multiple sessions per day) can lead to faster and stronger antidepressant effects. This approach could make brain stimulation therapies more accessible, efficient, and scalable for individuals with TRD.

The Future of Depression Treatment

This research is a significant step forward in neuromodulation therapy for depression. While more studies are needed to compare aTBS with traditional once-daily treatments and explore long-term effects, the current findings suggest that accelerated brain stimulation could become a game-changer for TRD. 

Final Thoughts

For individuals who have exhausted standard treatment options, aTBS offers new hope. As brain stimulation technologies continue to evolve, more people may soon have access to adequate, non-invasive alternatives for managing depression.

Could accelerated theta-burst stimulation be the future of depression treatment? Let’s keep an eye on this exciting field of research.

Reference

Ramos, M. R. F., Goerigk, S., da Silva, V. A., Cavendish, B. A., Pinto, B. S., Papa, C. H. G., Resende, J. V., Klein, I., Carneiro, A. M., de Sousa, J. P., Vidal, K. S. M., Valiengo, L. C. L., Razza, L. B., Aparício, L. M., Martins, L., Borrione, L., Batista, M., Moran, N. K., dos Santos, L. A., … Brunoni, A. R. (2025). Accelerated Theta-Burst Stimulation for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2025.0013

How do you refer a patient or request an appointment to the UTHealth Houston Center for Interventional Psychiatry?

Second Opinion Intake Form – https://Go.uth.edu/CIPIntake.

Phone – (713) 486-2621

Fax – (713) 500-2728

E-mail – [email protected]