Electrophysiological Biomarkers in Accelerated TMS for Depression

NCT07615387 | Completed

• 1 other identifier: 37949
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates whether physiological signals recorded during transcranial magnetic stimulation (TMS) can predict which patients with major depression respond to treatment. Thirty-two adults with major depressive disorder receive an accelerated TMS protocol targeting the dorsomedial prefrontal cortex using a double-cone coil, delivered as four sessions per day over five to eight days. Heart rate is continuously monitored throughout every stimulation session using a chest-strap sensor, and electroencephalography (EEG) is recorded before and after treatment. Heart-brain coupling was assessed in a separate dedicated session after the target stimulation dose was reached.The primary clinical outcome is the change in depression severity measured by the Hamilton Depression Rating Scale (HAMD-17) from baseline to post-treatment. Prespecified physiological outcomes include stimulation-evoked heart rate deceleration, resting-state EEG parameters, and heart-brain coupling metrics. The aim is to evaluate whether these electrophysiological measures index target engagement and predict antidepressant response, potentially supporting their use as functional biomarkers for personalizing accelerated TMS in depression.

Conditions

Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Depression Rating Scale (HAMD-17) Score

  Depression severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and within 1 week after completion of the accelerated iTBS course. The HAMD-17 is a clinician-administered scale; scores range from 0 to 52, with higher scores indicating more severe depression. Treatment response was defined as a 50% or greater reduction from baseline HAMD-17 score, and remission as a post-treatment HAMD-17 score of 7 or lower.

  Baseline, Day 5, and Day 8 for extended courses

Secondary Outcomes (10)

• Heart rate deceleration during stimulation

  Through completion of the treatment course, up to 8 days

• Change in Beck Depression Inventory (BDI)

  Baseline, Day 5, and Day 8 for extended courses

• Change in Beck Anxiety Inventory (BAI)

  Baseline, Day 5, and Day 8 for extended courses

• Change in Beck Scale for Suicide Ideation (BSS)

  Baseline, Day 5, and Day 8 for extended courses

• Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) Total Score

  Baseline, Day 5, and Day 8 for extended courses

Study Arms (1)

Accelerated bilateral dmPFC-iTBS with double-cone coil

EXPERIMENTAL

Participants received accelerated bilateral intermittent theta-burst stimulation (iTBS) targeting the dorsomedial prefrontal cortex (dmPFC) using a Cool DB-80 double-cone coil. Treatment consisted of four sessions per day, delivering 1,200 pulses per session (600 pulses per hemisphere, applied sequentially to left and right dmPFC), at 120% of resting motor threshold. The total course comprised 20 to 30 sessions over 5 to 8 days.

Device: Accelerated bilateral dmPFC-iTBS

Interventions

Accelerated bilateral dmPFC-iTBS DEVICE

Stimulation was delivered using a MagPro R30 stimulator equipped with a Cool DB-80 double-cone coil (MagVenture A/S, Farum, Denmark). The stimulation site was localized using the 25% nasion-inion scalp heuristic for dorsomedial prefrontal cortex (dmPFC) targeting. The intermittent theta-burst stimulation (iTBS) protocol consisted of triplet 50 Hz bursts repeated at 5 Hz, applied as 2-second trains with 8-second inter-train intervals. Each session delivered 600 pulses sequentially to the left and right dmPFC (1,200 pulses per session), at a target intensity of 120% of the hemisphere-specific resting motor threshold. Four sessions were delivered per day with approximately 50-minute inter-session intervals. The total treatment course was 20 sessions over 5 days, extended to 30 sessions over 8 days for partial responders.

Accelerated bilateral dmPFC-iTBS with double-cone coil

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 65 years
• Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of major depressive disorder, of at least moderate severity, confirmed by structured psychiatric interview
• Insufficient response to at least one adequate trials of antidepressant pharmacotherapy during the current episode
• Stable psychotropic medication regimen for at least 4 weeks prior to enrollment
• Ability to provide written informed consent

You may not qualify if:

• Cardiac arrhythmia or use of antiarrhythmic medication
• Benzodiazepine use exceeding the equivalent of 1 mg/day lorazepam
• Active suicidal ideation
• Comorbid psychiatric disorders other than anxiety disorders (including bipolar disorder, psychotic disorders, substance use disorders, and primary obsessive-compulsive disorder)
• Standard contraindications to transcranial magnetic stimulation, including history of seizure, intracranial metal implants, cochlear implants, or implanted neurostimulators
• Pregnancy
• Severe or unstable medical illness

Sponsors & Collaborators

• Istanbul University - Cerrahpasa: lead

Study Sites (1)

Istanbul University-Cerrahpaşa Cerrahpaşa Medical Faculty Psychiatry Department

Istanbul, Bakırköy, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 29, 2026
• Study Start: June 13, 2024
• Primary Completion: March 14, 2025
• Study Completion: April 14, 2025
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)