Treatment Resistant Depression (TRD)NCT07264452
Comparison of the Efficacy of Accelerated Intermittent Theta Burst Stimulation and Accelerated Continuous Theta Burst Stimulation in Patients With Treatment-Resistant Depression
A study testing Transcranial Magnetic Stimulation with figure-eight coil in people with Treatment Resistant Depression (TRD) and Transcranial Magnetic Stimulation, run by Ataturk University at 1 site in Turkey (Türkiye).
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Treatment Resistant Depression (TRD), Transcranial Magnetic Stimulation, Accelerated Protocol
- What is being tested?
- Transcranial Magnetic Stimulation with figure-eight coil
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 15 Nov 2025to 15 Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 to 65 years old
- Patients diagnosed with Major Depressive Disorder according to DSM 5 and the severity of their illness
- Scoring 7 points or more on the Maudsley staging method
- Having depression unresponsive to 2 different antidepressants
- No clinical mental retardation
- Agree to participate in the study
Show all 10Show fewer
- Hamilton Depression Rating Scale-17 [HDRS] score of 20 or higher
- Montgomery Asberg Depression Rating Scale [MADRS] score of 20 or above
- Being right hand dominant
- Having used the same antidepressant at the same dose for the last 4 weeks
Who cannot join
- 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)
- Having a foreign body such as a pacemaker, intracranial implant that can magnetically interact
- Hearing and visual impairments that prevent communication
- Unstable or acute medical conditions
- Pregnancy or breastfeeding
- Having a primary psychiatric disorder other than major depressive disorder
- Being diagnosed with severe MDD with psychotic features
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Ataturk University
Erzurum, 25240
Mahmut Balamur, research assistant doctor, +905350705623, m.balamur5@gmail.com
About this study
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.
Read the 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.
- Conditions
- Treatment Resistant Depression (TRD), Transcranial Magnetic Stimulation, Accelerated Protocol, Intermittent Theta Burst Stimulation, Continuous Theta Burst Stimulation, Unilateral rTMS
- Being tested
- Transcranial Magnetic Stimulation with figure-eight coil
- Keywords
- Treatment Resistant Depression (TRD), Transcranial Magnetic Stimulation, Accelerated protocol, intermittent theta burst stimulation, Continuous theta burst stimulation, Unilateral rTMS, unipolar major depressive disorder, non-invasive brain stimulation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation with figure-eight coilDevice
Also called A group
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.
Transcranial Magnetic Stimulation with figure-eight coilDevice
Also called B group
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.
| Study group | Role | What they receive |
|---|---|---|
| Itbs | Active comparator | iTBS with eight digit coils to the left dorsolateral prefrontal cortex. Receives: Device: Transcranial Magnetic Stimulation with figure-eight coil |
| ctbs | Active comparator | cTBS with a figure-of-eight coil to the right dorsolateral prefrontal cortex. Receives: Device: Transcranial Magnetic Stimulation with figure-eight coil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression severity
The Montgomery-Asberg Depression Rating Scale. The minimum and maximum scores are 0-60. Higher scores mean a worse outcome.
Measured: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Depression severity
The Hamilton Depression Rating Scale-17. The minimum and maximum scores are 0-51. Higher scores mean a worse outcome.
Measured: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Secondary outcomes (7)
Anxiety severity
Hamilton Anxiety Rating Scale. The minimum and maximum scores are 0-56. Higher scores mean a worse outcome.
Measured: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Suicidal ideation score of The Hamilton Depression Rating Scale-17
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.
Measured: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Suicidal ideation score of The Montgomery-Asberg Depression Rating Scale
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.
Measured: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Insomnia Severity
It is measured with the Pittsburgh Sleep Quality Index (PSQI). The minimum and maximum scores are 0-21. Higher scores mean a worse outcome.
Measured: pretreatment, 4 weeks, 10 weeks and 14 weeks
Insomnia Severity
It is measured with the Insomnia Severity Index (ISI). The minimum and maximum scores are 0-28. Higher scores mean a worse outcome.
Measured: pretreatment, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Cognitive Assessment
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.
Measured: pretreatment and 14 weeks
Functionality Severity
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.
Measured: pretreatment, 2 weeks and 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2025
- Study start15 Nov 2025
- Primary completion15 Nov 2026 (estimated)
- Study completion15 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant Depression (TRD)Studies of the same condition, open and under way.
- More trials run by Ataturk UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ataturk University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Omer Faruk Uygur, Ataturk University
- Investigators
- Omer Faruk UYGUR, Associate professor doctor, Principal investigator, Ataturk University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07264452
- Sponsor's protocol ID
- 2025-08/08
- Other IDs
- Atatürk University
- Status last verified
- Dec 2025
- First submitted
- 21 Nov 2025
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Efficacy of Accelerated Intermittent Theta Burst Stimulation and Accelerated Continuous Theta Burst Stimulation in Patients With Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT07264452
- Acronym / sponsor ID
- 2025-08/08
- Conditions
- Treatment Resistant Depression (TRD), Transcranial Magnetic Stimulation, Accelerated Protocol, Intermittent Theta Burst Stimulation, Continuous Theta Burst Stimulation, Unilateral rTMS
- Keywords
- Treatment Resistant Depression (TRD), Transcranial Magnetic Stimulation, Accelerated protocol, intermittent theta burst stimulation, Continuous theta burst stimulation, Unilateral rTMS, unipolar major depressive disorder, non-invasive brain stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ataturk UniversityUniversity, hospital or other
- Study start
- 15 Nov 2025 (actual)
- Primary completion
- 15 Nov 2026 (estimated)
- Study completion
- 15 Jan 2027 (estimated)
- First posted
- 4 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Itbs | Active comparator | Device: Transcranial Magnetic Stimulation with figure-eight coiliTBS with eight digit coils to the left dorsolateral prefrontal cortex. |
| ctbs | Active comparator | Device: Transcranial Magnetic Stimulation with figure-eight coilcTBS with a figure-of-eight coil to the right dorsolateral prefrontal cortex. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 18 to 65 years old
- Patients diagnosed with Major Depressive Disorder according to DSM 5 and the severity of their illness
- Scoring 7 points or more on the Maudsley staging method
- Having depression unresponsive to 2 different antidepressants
- No clinical mental retardation
Key exclusion criteria (7 listed)
- 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)
- Having a foreign body such as a pacemaker, intracranial implant that can magnetically interact
- Hearing and visual impairments that prevent communication
- Unstable or acute medical conditions
- Pregnancy or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation with figure-eight coilAlso: A groupA 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. | Device | Itbs |
| Transcranial Magnetic Stimulation with figure-eight coilAlso: B groupThe 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. | Device | ctbs |
Primary outcome
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.
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.
7 secondary outcomes
Anxiety severity
Time frame: 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 of The Montgomery-Asberg Depression Rating Scale
Time frame: 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
Insomnia Severity
Time frame: pretreatment, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks
Cognitive Assessment
Time frame: pretreatment and 14 weeks
Functionality Severity
Time frame: pretreatment, 2 weeks and 14 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Omer Faruk UYGUR, Associate professor doctor principal investigator
Ataturk University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation with figure-eight coil in people with Treatment Resistant Depression (TRD) and Transcranial Magnetic Stimulation, run by Ataturk University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mahmut Balamur, research assistant doctor (+905350705623, m.balamur5@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depression severity (time frame: pretreatment, 1 week, 2 weeks, 4 weeks, 6 weeks, 10 weeks and 14 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2025.