Accelerated Transcranial Magnetic Stimulation in Treatment-Resistant Depressed Patients

NCT ID: NCT06783361

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2025-08-01

Brief Summary

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).

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.

Conditions

Treatment Resistant Depression (TRD); Transcranial Magnetic Stimulation; Accelerated Protocol; Sham-controlled; Bilateral rTMS; Unipolar Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation with figure-eight coil

Intervention Type: DEVICE

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.

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.

Group Type: SHAM_COMPARATOR

Transcranial Magnetic Stimulation with figure-eight coil

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

Other Intervention Names

active treatment; sham control group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ataturk University

OTHER

Sponsor Role: lead

Responsible Party

Omer Faruk Uygur

associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Omer Faruk UYGUR, Associate professor doctor

Role: PRINCIPAL_INVESTIGATOR

Ataturk University

Locations

Ataturk University

Erzurum, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

Other Identifiers

Atatürk University

Identifier Type: OTHER

Identifier Source: secondary_id

2024-04/10

Identifier Type: -

Identifier Source: org_study_id