Efficacy and Safety of a Theta Burst Stimulation Protocol of Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Depression

April 10, 2026 updated by: Jung-Sun Lee

A Prospective, Multicenter, Randomized, Single-Blind, Exploratory Clinical Trial to Validate the Efficacy and Safety and Predict Treatment Response of a Theta Burst Stimulation Protocol of Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Depression

This study will evaluate the efficacy and safety of a theta burst stimulation (TBS) protocol of repetitive transcranial magnetic stimulation (rTMS) in adults with treatment-resistant depression. Participants will be randomized to either antidepressant treatment plus active rTMS TBS or antidepressant treatment plus sham stimulation for the first 10 sessions followed by active rTMS TBS for the next 10 sessions. The main objective is to compare the change in Hamilton Depression Rating Scale (HAM-D) total score after 10 treatment sessions between groups and to explore predictors of treatment response.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, multicenter, randomized, double-blind, exploratory clinical trial evaluating the efficacy and safety of rTMS theta burst stimulation (TBS) in patients with depression.

A total of 120 participants will be enrolled, including 80 adults (≥19 years) with treatment-resistant depression and 40 adolescents (15-17 years) with depressive disorders. Participants will be stratified by age group and randomized in a 1:1 ratio to one of two treatment arms.

In the combined treatment arm, participants will receive antidepressant therapy plus active bilateral sequential TBS (bsTBS) for 20 sessions over approximately 4 to 7 weeks. In the comparator arm, participants will receive antidepressant therapy plus sham stimulation for the first 10 sessions, followed by active TBS for the remaining 10 sessions.

The primary outcome is the change in depressive symptom severity after 10 treatment sessions, measured by HAM-D in adults and age-appropriate scales in adolescents. Secondary outcomes include sleep, cognitive function, global clinical improvement, social functioning, and neuroimaging biomarkers. Safety outcomes include adverse events and suicidal ideation assessments.

This study aims to explore the efficacy of TBS across different age groups and to identify predictors of treatment response.

Study Type

Interventional

Enrollment (Estimated)

120

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 Contact

  • Name: Jungsun Lee, MD, PhD
  • Phone Number: +82-2-3010-3422
  • Email: ljssmh@gmail.com

Study Locations

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥15 years
  • Diagnosis of depressive disorder based on DSM criteria
  • Adults: treatment-resistant depression
  • Adolescents: depressive disorder requiring treatment
  • Moderate or greater depressive symptoms
  • Adults: HAM-D ≥17, MADRS ≥14
  • Adolescents: age-appropriate validated scale (e.g., CDRS-R)
  • Currently receiving or eligible for antidepressant treatment

Exclusion Criteria:

  • Bipolar disorder, schizophrenia, or psychotic disorder
  • Substance use disorder (recent)
  • Neurological disorders (e.g., epilepsy, brain injury)
  • Severe medical illness
  • Metal implants or contraindications to TMS
  • Pacemaker or implanted device
  • Prior rTMS or ECT
  • Pregnancy
  • Any condition deemed unsuitable by investigator

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Antidepressant + Active rTMS TBS
Drug: antidepressant therapy
Participants continue their baseline antidepressant regimen. Changes are restricted except for safety reasons.
Device: Active rTMS Theta Burst Stimulation
Bilateral sequential TBS targeting the dorsolateral prefrontal cortex (left iTBS, right cTBS), delivered over 20 sessions.
Sham Comparator: Antidepressant + Sham then Active rTMS TBS
Drug: antidepressant therapy
Participants continue their baseline antidepressant regimen. Changes are restricted except for safety reasons.
Device: Sham Stimulation
Sham stimulation is delivered for the first 10 sessions using coil positioning that prevents effective stimulation, followed by active rTMS TBS for the next 10 sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Depressive Symptom Severity
Time Frame: Baseline and at 10 treatment sessions (~ 2 weeks)
Change in depressive symptom severity measured by the Hamilton Depression Rating Scale (HAM-D; range 0-52, higher scores indicate more severe depression)
Baseline and at 10 treatment sessions (~ 2 weeks)

Collaborators and Investigators

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

Sponsor

Jung-Sun Lee

Collaborators

Seoul St. Mary's Hospital, The Catholic University
Seoul National University Hospital
Korea Health Industry Development Institute
Nowon Eulji Medical Center, Eulji University

Investigators

  • Principal Investigator: Jungsun Lee, MD, PhD, Asan Medical Center

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 (Estimated)

May 1, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

April 5, 2026

First Submitted That Met QC Criteria

April 10, 2026

First Posted (Actual)

April 14, 2026

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-0378

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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