Electrophysiological Biomarkers in Accelerated TMS for Depression

May 22, 2026 updated by: Ali Tarık Altunç, Istanbul University - Cerrahpasa

Electrophysiological Biomarkers of Treatment Response in Major Depressive Disorder Patients Receiving Accelerated Transcranial Magnetic Stimulation

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.

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.

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.
32

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

  • Turkey (Türkiye)
    • Bakırköy
      • Istanbul, Bakırköy, Turkey (Türkiye)
        • Istanbul University-Cerrahpaşa Cerrahpaşa Medical Faculty Psychiatry Department

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

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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.
Experimental: Accelerated bilateral dmPFC-iTBS with double-cone coil
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
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.

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
Change in Hamilton Depression Rating Scale (HAMD-17) Score
Time Frame: Baseline, Day 5, and Day 8 for extended courses
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 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
Heart rate deceleration during stimulation
Time Frame: Through completion of the treatment course, up to 8 days
Heart rate was continuously sampled at 1-second intervals using a Polar H10 chest strap during every stimulation session. Heart rate deceleration (HRD) was calculated as the percentage reduction from the 1-minute pre-stimulation baseline heart rate to the mean stimulation heart rate, using the formula: HRD (%) = [(HR_baseline - HR_stimulation) / HR_baseline] x 100. HRD was computed across four parameters (all left-sided sessions, all right-sided sessions, highest-intensity left-sided sessions, highest-intensity right-sided sessions) and averaged per participant. Higher values indicate greater stimulation-induced heart rate deceleration.
Through completion of the treatment course, up to 8 days
Change in Beck Depression Inventory (BDI)
Time Frame: Baseline, Day 5, and Day 8 for extended courses
Beck Depression Inventory (BDI), a self-report scale; total scores range from 0 to 63, with higher scores indicating more severe depression.
Baseline, Day 5, and Day 8 for extended courses
Change in Beck Anxiety Inventory (BAI)
Time Frame: Baseline, Day 5, and Day 8 for extended courses
Beck Anxiety Inventory (BAI), a self-report scale; total scores range from 0 to 63, with higher scores indicating more severe anxiety.
Baseline, Day 5, and Day 8 for extended courses
Change in Beck Scale for Suicide Ideation (BSS)
Time Frame: Baseline, Day 5, and Day 8 for extended courses
Beck Scale for Suicide Ideation (BSS), a self-report scale; total scores range from 0 to 38, with higher scores indicating greater suicidal ideation.
Baseline, Day 5, and Day 8 for extended courses
Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) Total Score
Time Frame: Baseline, Day 5, and Day 8 for extended courses
Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16); total scores range from 0 to 27, with higher scores indicating more severe depression.
Baseline, Day 5, and Day 8 for extended courses
Change in Clinical Global Impression - Severity (CGI-S)
Time Frame: Baseline, Day 5, and Day 8 for extended courses
Clinical Global Impression - Severity (CGI-S); scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients), with higher scores indicating greater illness severity.
Baseline, Day 5, and Day 8 for extended courses
Hamilton Depression Rating Scale (HAMD-17) Total Score at 30-Day Follow-up
Time Frame: 30 days post-treatment
17-item Hamilton Depression Rating Scale (HAMD-17) assessed 30 days after completion of treatment; total scores range from 0 to 52, with higher scores indicating more severe depression.
30 days post-treatment
Resting State Quantitative EEG (qEEG) Spectral Power and Theta Cordance
Time Frame: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Absolute spectral power in the delta, theta, alpha, and beta frequency bands, derived from quantitative resting-state EEG (qEEG) analysis. Power was computed across standard electrode regions. Prefrontal theta cordance, a quantitative EEG measure combining absolute and relative theta-band power at prefrontal electrodes, derived from resting-state qEEG analysis.
Baseline and completion of treatment (Day5 or Day8 for extended courses)
Heart-Brain Coupling (HBC): Heart Rate Oscillation Power at the Stimulation Frequency
Time Frame: Single dedicated measurement session after the target dose was reached, up to Day 8
Heart-brain coupling (HBC), a parameter quantifying the strength of stimulation-induced heart rate deceleration, computed as the mean oscillation power of cardiac rate at the frequency determined by the stimulation train interval (Dijkstra et al., 2023). HBC ranges from 0 to 1. Measurements were obtained in a dedicated session using a 10 Hz protocol (50 pulses per train, 5-second train duration, 15 trains, 11-second inter-train interval), recorded with a Polar H10 chest strap and the HeartBrainConnect application. HBC was assessed sequentially at four sites per participant: left dmPFC, left dorsolateral prefrontal cortex (DLPFC), right dmPFC and right DLPFC. For each site, stimulation began at 28% below target intensity and increased by 2% per train, yielding 15 HBC values that were averaged to produce a per-site HBC value.
Single dedicated measurement session after the target dose was reached, up to Day 8
EEG Microstate Temporal Parameters
Time Frame: Baseline and completion of treatment (Day5 or Day8 for extended courses)
Temporal parameters of the canonical resting-state EEG microstate classes (A, B, C, and D), including mean duration (milliseconds), occurrence (mean appearances per second), time coverage (percentage of recording time), and transition probabilities between classes. Parameters were derived from microstate segmentation of resting-state EEG recordings.
Baseline and completion of treatment (Day5 or Day8 for extended courses)

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.
Istanbul University - Cerrahpasa

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.
June 13, 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.
March 14, 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.
April 14, 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).
May 18, 2026

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.
May 22, 2026

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.
May 29, 2026

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.
May 29, 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.
May 22, 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.
May 1, 2026

More Information

Terms related to this study

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.
  • 37949

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

De-identified individual-level data are not publicly available due to privacy and ethical restrictions on sensitive clinical data, but may be available from the corresponding author upon reasonable request and with appropriate ethics committee approval.

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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Conditions

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