Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study

NCT03680781 | Completed Results FDA Device

• 1 other identifier: IRB-44150
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Depression Rating Scale 21-Item Score

  A 21 item clinical assessment tool used to rate a patient's level of depression. The total scores range from 0 to 63 with higher scores indicating worse depression.

  Difference between baseline and follow up at one month after the final aiTBS treatment (on day 5)

Secondary Outcomes (6)

• Change in Hamilton Rating Scale for Depression (HAMD-17)

  Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment

• Change in The Scale for Suicide Ideation

  Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment

• Change in Hamilton Rating Scale for Depression (HAMD-6)

  Every day of stimulation on days (visits) 1, 2, 3, 4, and 5

• Change From Baseline Functional Connectivity

  Baseline, immediately post-treatment, 4 weeks post-treatment

• Change in Beck Depression Inventory (BDI)

  Baseline, immediately post-treatment, 4 weeks post-treatment

Study Arms (1)

Accelerated theta burst treatment

EXPERIMENTAL

All participants will receive theta-burst TMS.

Device: Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC; Device: Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC

Interventions

Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC DEVICE

Participants will receive iTBS to the left DLPFC and will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the L-DLPFC or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device.

Accelerated theta burst treatment

Intermittent theta-burst stimulation (iTBS) delivered to the bilateral DLPFC DEVICE

Participants will receive iTBS to bilateral DLPFC. The DLPFC will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the L-DLPFC or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device.

Accelerated theta burst treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 to 75 years of age.
• Able to provide informed consent.
• Diagnosed with Major Depressive Disorder (MDD) or bipolar affective disorder 2 and currently experiencing a Major Depressive Episode (MDE).
• prior exposure to rTMS
• Participants must qualify as "moderate or severe treatment refractory" using the Maudsley staging method.
• Participants may continue antidepressant regimen, but must be stable for 6 weeks prior to enrollment in the study. They must maintain that same antidepressant regimen throughout the study duration.
• Participants are required to have a stable psychiatrist for the duration of study enrollment.

You may not qualify if:

• History of MI, CABG, CHF, or other cardiac history
• Any neurological conditions
• History of epilepsy
• OCD
• Independent sleep disorder
• Autism Spectrum Disorder

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

Palo Alto, California, 94305, United States

Location

Related Publications (6)

• George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.

  PMID: 20439832 BACKGROUND

• George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.

  PMID: 8547583 BACKGROUND

• Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.

  PMID: 8684201 BACKGROUND

• Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.

  PMID: 26850210 BACKGROUND

• Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.

  PMID: 25281475 BACKGROUND

• Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.

  PMID: 25450537 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Protocol Director
• Organization: Stanford University

nbassano@stanford.edu

650-800-6920

Study Officials

• Gregory Sahlem, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor, Department of Psychiatry & Behavioral Sciences

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: September 21, 2018
• Study Start: April 13, 2018
• Primary Completion: December 2, 2024
• Study Completion: December 2, 2024
• Last Updated: April 21, 2026
• Results First Posted: April 21, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)