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

March 30, 2026 updated by: Gregory Sahlem, Stanford University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study will investigate the efficacy of a further modified protocol, creating a more rapid form of the treatment and look at the change in neuroimaging biomarkers. In particular, this study will determine the efficacy of re-treatment in individuals who have already experienced benefit of the accelerated protocol to ensure results can be repeated.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94305
        • Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Accelerated theta burst treatment
All participants will receive theta-burst TMS.
Device: Intermittent theta-burst stimulation (iTBS) delivered to the L-DLPFC

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.

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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hamilton Depression Rating Scale 21-Item Score
Time Frame: Difference between baseline and follow up at one month after the final aiTBS treatment (on day 5)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hamilton Rating Scale for Depression (HAMD-17)
Time Frame: Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
The HAMD-17 is a 17-item rating scale questionnaire administered by clinicians to rate a patient's level of depression . The total scores range from 0 to 52 with higher scores indicating worse depression.
Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
Change in The Scale for Suicide Ideation
Time Frame: Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
A rating scale that measures the current intensity of specific attitudes, behaviors, and plans to commit suicide. The total scores range from 0 to 38 with higher scores indicating greater suicidality.
Baseline, immediately post treatment, 2 weeks post treatment, 4 weeks post treatment
Change in Hamilton Rating Scale for Depression (HAMD-6)
Time Frame: Every day of stimulation on days (visits) 1, 2, 3, 4, and 5
The HAMD-6 is a shorter, six-item version of the Hamilton Depression Rating Scale (HAMD-D) that measures core symptoms of major depressive disorder, such as depressed mood, guilt and anxiety. The total scores range from 0 to 22 with higher scores indicating worse depression.
Every day of stimulation on days (visits) 1, 2, 3, 4, and 5
Change From Baseline Functional Connectivity
Time Frame: Baseline, immediately post-treatment, 4 weeks post-treatment
We will assess functional connectivity as seen on resting state fMRI, between the subcallosal cingulate to the default mode network and within the default mode network.
Baseline, immediately post-treatment, 4 weeks post-treatment
Change in Beck Depression Inventory (BDI)
Time Frame: Baseline, immediately post-treatment, 4 weeks post-treatment
The Beck Depression Inventory (BDI) is a 21-item self-report questionnaire used to measure the severity of depression symptoms. The total scores range from 0 to 63 with higher scores indicating worse depression.
Baseline, immediately post-treatment, 4 weeks post-treatment
Change in Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: Baseline, immediate post-treatment, 4 weeks post-treatment
The MADRS (Montgomery-Åsberg Depression Rating Scale) is a 10-item diagnostic tool used by clinicians to assess the severity of depression by scoring symptoms on a 0-60 scale with higher scores indicating worse depression.
Baseline, immediate post-treatment, 4 weeks post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Investigators

  • Principal Investigator: Gregory Sahlem, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 13, 2018

Primary Completion (Actual)

December 2, 2024

Study Completion (Actual)

December 2, 2024

Study Registration Dates

First Submitted

September 10, 2018

First Submitted That Met QC Criteria

September 20, 2018

First Posted (Actual)

September 21, 2018

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

March 30, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-44150

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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