Comparison of the Efficacy of Accelerated Intermittent Theta Burst Stimulation and Accelerated Continuous Theta Burst Stimulation in Patients With Treatment-Resistant Depression

December 2, 2025 updated by: Omer Faruk Uygur, Ataturk University
In recent years, research on the effectiveness of transcranial magnetic stimulation (TMS) in patients with treatment-resistant depression (RTD) has been steadily increasing. The aim of this study was to examine the effectiveness of accelerated unilateral application of two different forms of theta burst stimulation (TBU), a variation of repetitive TMU (rTMS)-intermittent TBU (iTBU) and continuous TBU (cTBU)-in TDD patients. The study aimed to compare the advantages of iTBU and cTBU protocols on depression, suicidal thoughts, anxiety levels, sleep disturbances, cognitive performance, and overall functioning following a two-week intensive treatment period and a 12-week follow-up period.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Major depressive disorder (MDD) is the most common form of mood disorders that is frequently encountered in the society, has high recurrence and chronicity rates, and can lead to significant physical, cognitive, and psychosocial dysfunction in individuals. Although there is no single universally accepted definition for treatment-resistant depression (TRD), one of the most frequently used definitions is "failure to respond to at least two different antidepressant treatments for a sufficient duration and at an appropriate dose." Repetitive transcranial magnetic stimulation (rTMS) applied to the left and/or right dorsolateral prefrontal cortex (DLPFC) stands out as an alternative treatment approach in patients with TRD. One of these methods, theta-burst stimulation (TBS), is a non-invasive neuromodulation method approved by the US Food and Drug Administration (FDA) for treatment-resistant depression. Current methodological advances have enabled current TBS protocols to; Therapeutic efficacy can be enhanced by applying sessions multiple times a day, increasing the stimulation dose, and more precisely targeting the bilateral DLPFC. In addition to intermittent TBS (iTBS), continuous TBS (cTBS) protocols applied to the right DLPFC have also been reported to offer therapeutic potential in patients with TDD. Several studies have demonstrated that protocols consisting of 1,800 pulses produce lasting changes in cortical excitability and effectively trigger targeted neuroplastic mechanisms.

The study was planned to be conducted with patients who presented to the Atatürk University Faculty of Medicine, Department of Psychiatry Outpatient Clinic and were diagnosed with major depressive disorder (MDD) according to the American Psychiatric Association's DSM-5 diagnostic criteria. Participants were randomly assigned to two groups. In this single-blind, parallel study, one group was scheduled to receive a total of 50 sessions of iTBS to the left dorsolateral prefrontal cortex (left-DLPFC), while the other group received 50 sessions of cTBS to the right-DLPFC.

Clinical assessments of patients will be conducted at baseline, mid-treatment, at the end of treatment, and at weeks 2, 4, 8, and 12 post-treatment. Depressive symptoms will be measured with the HAM-D and MADRS, anxiety with the Hamilton Anxiety Rating Scale (HAM-A), sleep disturbances with the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), cognitive functions with the Montreal Cognitive Assessment Scale (MoCA), and functioning with the Brief Functioning Assessment Scale (BFAS). Participants were expected to maintain their current psychotropic medication at stable doses throughout the study.

Study Type

Interventional

Enrollment (Estimated)

60

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: Mahmut Balamur, research assistant doctor
  • Phone Number: +905350705623
  • Email: m.balamur5@gmail.com

Study Contact Backup

  • Name: Omer Faruk UYGUR, Associate professor doctor
  • Phone Number: +905456161625
  • Email: drofuygur@hotmail.com

Study Locations

  • Turkey (Türkiye)
      • Erzurum, Turkey (Türkiye), 25240
        • Recruiting
        • Ataturk University
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. 18 to 65 years old
  2. Patients diagnosed with Major Depressive Disorder according to DSM 5 and the severity of their illness
  3. Scoring 7 points or more on the Maudsley staging method
  4. Having depression unresponsive to 2 different antidepressants
  5. No clinical mental retardation
  6. Agree to participate in the study
  7. Hamilton Depression Rating Scale-17 [HDRS] score of 20 or higher
  8. Montgomery Asberg Depression Rating Scale [MADRS] score of 20 or above
  9. Being right hand dominant
  10. Having used the same antidepressant at the same dose for the last 4 weeks

Exclusion Criteria:

  1. Diagnosed with a neurological or metabolic disease that affects cognitive functions (Systemic diseases such as diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic renal failure, Parkinson's disease, multiple sclerosis, polyneuropathy, inflammatory rheumatologic disease and malignancies)
  2. Having a foreign body such as a pacemaker, intracranial implant that can magnetically interact
  3. Hearing and visual impairments that prevent communication
  4. Unstable or acute medical conditions
  5. Pregnancy or breastfeeding
  6. Having a primary psychiatric disorder other than major depressive disorder
  7. Being diagnosed with severe MDD with psychotic features

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
Active Comparator: Itbs
iTBS with eight digit coils to the left dorsolateral prefrontal cortex.
Device: Transcranial Magnetic Stimulation with figure-eight coil
A total of 50 sessions will be administered to at least 30 patients, five sessions per day, five days a week for two weeks. There will be at least a 30-minute rest period between each session. One session for Group A involves a 5 Hz frequency intermittent theta burst stimulation (iTBS) protocol applied to the left DLPFC at 90-110% motor threshold.
Other Names:
  • A group
Device: Transcranial Magnetic Stimulation with figure-eight coil
The other patient group (Group B), consisting of at least 30 individuals, will receive 5 sessions per day, 5 days a week, for 2 weeks, for a total of 50 sessions. There will be at least a 30-minute rest period between each session. Group B will receive a 5 Hz, continuous theta burst stimulation (cTBS) protocol to the right DLPFC at 80% motor threshold.
Other Names:
  • B group
Active Comparator: ctbs
cTBS with a figure-of-eight coil to the right dorsolateral prefrontal cortex.
Device: Transcranial Magnetic Stimulation with figure-eight coil
A total of 50 sessions will be administered to at least 30 patients, five sessions per day, five days a week for two weeks. There will be at least a 30-minute rest period between each session. One session for Group A involves a 5 Hz frequency intermittent theta burst stimulation (iTBS) protocol applied to the left DLPFC at 90-110% motor threshold.
Other Names:
  • A group
Device: Transcranial Magnetic Stimulation with figure-eight coil
The other patient group (Group B), consisting of at least 30 individuals, will receive 5 sessions per day, 5 days a week, for 2 weeks, for a total of 50 sessions. There will be at least a 30-minute rest period between each session. Group B will receive a 5 Hz, continuous theta burst stimulation (cTBS) protocol to the right DLPFC at 80% motor threshold.
Other Names:
  • B group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Depression severity
Time Frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
The Montgomery-Asberg Depression Rating Scale. The minimum and maximum scores are 0-60. Higher scores mean a worse outcome.
pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Depression severity
Time Frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
The Hamilton Depression Rating Scale-17. The minimum and maximum scores are 0-51. Higher scores mean a worse outcome.
pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anxiety severity
Time Frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Hamilton Anxiety Rating Scale. The minimum and maximum scores are 0-56. Higher scores mean a worse outcome.
pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Suicidal ideation score of The Hamilton Depression Rating Scale-17
Time Frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Suicidal ideation score on the third question of the Hamilton Depression Rating Scale-17. The minimum and maximum scores are 0-4. Higher scores mean a worse outcome.
pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Suicidal ideation score of The Montgomery-Asberg Depression Rating Scale
Time Frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Suicidal ideation score on the tenth question of the Montgomery-Asberg Depression Rating Scale. Minimum and maximum scores range from 0-6. Higher scores mean a worse outcome.
pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Insomnia Severity
Time Frame: pretreatment, 4 weeks, 10 weeks and 14 weeks
It is measured with the Pittsburgh Sleep Quality Index (PSQI). The minimum and maximum scores are 0-21. Higher scores mean a worse outcome.
pretreatment, 4 weeks, 10 weeks and 14 weeks
Insomnia Severity
Time Frame: pretreatment, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
It is measured with the Insomnia Severity Index (ISI). The minimum and maximum scores are 0-28. Higher scores mean a worse outcome.
pretreatment, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Cognitive Assessment
Time Frame: pretreatment and 14 weeks
Montreal Cognitive Assessment (MoCA) : The maximum score that can be obtained from the test is 30. A total score of 21 and above indicates that the participant is within normal limits.
pretreatment and 14 weeks
Functionality Severity
Time Frame: pretreatment, 2 weeks and 14 weeks
Functioning Assessment Short Test (FAST): It is used to measure patients' functionality. The minimum and maximum scores are 0-66. Higher scores mean a worse outcome.
pretreatment, 2 weeks and 14 weeks

Collaborators and Investigators

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

Sponsor

Ataturk University

Investigators

  • Principal Investigator: Omer Faruk UYGUR, Associate professor doctor, Ataturk University

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)

November 15, 2025

Primary Completion (Estimated)

November 15, 2026

Study Completion (Estimated)

January 15, 2027

Study Registration Dates

First Submitted

November 21, 2025

First Submitted That Met QC Criteria

December 2, 2025

First Posted (Estimated)

December 4, 2025

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

December 2, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-08/08
  • Ataturk University (Other Identifier: Scientific Research Projects Coordination Centre)

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

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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