Accelerated Transcranial Magnetic Stimulation in Treatment-Resistant Depressed Patients

June 3, 2026 updated by: Omer Faruk Uygur, Ataturk University

Accelerated Transcranial Magnetic Stimulation in Treatment-Resistant Depressed Patients: Comparison Of The Effectiveness Of Bilateral Theta Bursts With Unilateral Theta Bursts

Depression is the leading cause of disability worldwide and around 800,000 suicides occur each year. According to the World Health Organization, major depressive disorder (MDD) is expected to be the leading cause of the global burden of disease by 2030. One third of MDD patients do not respond to first-line pharmacologic and psychotherapeutic antidepressant treatments. New antidepressant treatments that are safe, tolerable, fast-acting, durable and effective are needed. Transcranial magnetic stimulation (TMS) is a promising form of non-invasive brain stimulation with rapid antidepressant and suicide prevention effects in MDD. TMS applied to the left dorsolateral prefrontal cortex (DLPFC) is a non-invasive brain stimulation technique approved by the US Food and Drug Administration (FDA) for treatment-resistant depression. TMS involves passing an electric current through a magnetic coil placed on the surface of the scalp, producing a high-intensity magnetic field that travels through the scalp, skull and meninges, stimulating neuronal tissue. This in turn causes changes in functional connectivity. The mechanism of TMS on core depressive symptoms is hypothesized to be mediated in part through indirect inhibitory functional connectivity from the left DLPFC to the subgenual anterior cingulate cortex (sgACC).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The aim of this study was to investigate whether recurrent TMS (rTMS) and theta burst stimulation (TBS) are superior to each other when applied unilaterally and bilaterally in treatment-resistant MDD. As stated in the reference articles, a similar study was conducted unilaterally at Stanford University and achieved 70% remission rates. Our goal is that bilateral administration will result in longer treatment compliance and duration of effect compared to unilateral administration. This study aims to monitor the change in neurocognitive functions of patients with moderate to severe depression diagnosed with major depression according to DSM 5 criteria, whose treatment is prescribed by their physician as transcranial magnetic stimulation (TMS) and whose current pharmacological treatment is continued concurrently with TMS treatment, at the controls to be performed before TMS treatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks and 14 weeks after the start of TMS treatment. For this purpose, structured neuropsychological tests with Turkish validity and reliability studies will be applied to the patients. In addition, the study aims to evaluate whether there will be a decrease in the severity of depression after TMS treatment and whether there is any change in depression severity and symptoms in the 1st week, 2nd week, 4th week, 6th week, 8th week, 10th week and 14th week controls through the scales measuring the severity of depression to be applied to the patients participating in the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: A group
iTBS with eight digit coils to the left dorsolateral prefrontal cortex and 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 applied for 2 weeks, 5 sessions a day, 5 days a week. There will be at least 30 minutes rest time between each session. It includes first an intermittent theta burst (iTBS) protocol at a frequency of 5 Hz with 1800 pulses to the left DLPFC at 90% motor threshold, followed by a continuous theta burst (cTBS) protocol at a frequency of 5 Hz with 600 pulses to the right DLPFC at 80% motor threshold.
Other Names:
  • active treatment
Device: Transcranial Magnetic Stimulation with figure-eight coil
A total of 50 sessions will be applied for 2 weeks, 5 sessions a day, 5 days a week. There will be at least 30 minutes rest time between each session. One session will consist of a high frequency (5 Hz) intermittent theta burst (iTBS) of 1800 pulses at 90% motor threshold to the left DLPFC followed by a pseudo continuous theta burst (cTBS) of 600 pulses at 5 Hz frequency at 80% motor threshold to the right DLPFC. The sham cTBS treatment will be applied by placing the coil at a 45-degree angle to the application site.
Other Names:
  • sham control group
Sham Comparator: B group

iTBS with eight digit coils to the left dorsolateral prefrontal cortex and sham Sham cTBS with a figure-of-eight coil to the right dorsolateral prefrontal cortex.

The sham cTBS treatment will be administered by placing the coil at a 45-degree angle to the application site.
Device: Transcranial Magnetic Stimulation with figure-eight coil
A total of 50 sessions will be applied for 2 weeks, 5 sessions a day, 5 days a week. There will be at least 30 minutes rest time between each session. It includes first an intermittent theta burst (iTBS) protocol at a frequency of 5 Hz with 1800 pulses to the left DLPFC at 90% motor threshold, followed by a continuous theta burst (cTBS) protocol at a frequency of 5 Hz with 600 pulses to the right DLPFC at 80% motor threshold.
Other Names:
  • active treatment
Device: Transcranial Magnetic Stimulation with figure-eight coil
A total of 50 sessions will be applied for 2 weeks, 5 sessions a day, 5 days a week. There will be at least 30 minutes rest time between each session. One session will consist of a high frequency (5 Hz) intermittent theta burst (iTBS) of 1800 pulses at 90% motor threshold to the left DLPFC followed by a pseudo continuous theta burst (cTBS) of 600 pulses at 5 Hz frequency at 80% motor threshold to the right DLPFC. The sham cTBS treatment will be applied by placing the coil at a 45-degree angle to the application site.
Other Names:
  • sham control group

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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, 2 weeks, 4 weeks, 6 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, 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 Insomnia Severity Index (ISI). The minimum and maximum scores are 0-28. Higher scores mean a worse outcome.
pretreatment, 4 weeks, 10 weeks and 14 weeks
Cognitive Assessment
Time Frame: pretreatment, 4 weeks, 10 weeks 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, 4 weeks, 10 weeks and 14 weeks
Functionality Severity
Time Frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 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, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ataturk University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 13, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 17, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 20, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2024-04/10
  • Atatürk University (Other Identifier: Scientific Research Projects Coordination Unit)

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

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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