Major Depressive Disorder (MDD)
Conditions
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.
Interventions
DEVICEAccelerated 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.
Sponsors
Istanbul University - Cerrahpasa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HAMD-17) Score | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart rate deceleration during stimulation | 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. |
| Change in Beck Depression Inventory (BDI) | 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. |
| Change in Beck Anxiety Inventory (BAI) | 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. |
| Change in Beck Scale for Suicide Ideation (BSS) | 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. |
| Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR16) Total Score | 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. |
| Change in Clinical Global Impression - Severity (CGI-S) | 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. |
| Hamilton Depression Rating Scale (HAMD-17) Total Score at 30-Day Follow-up | 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. |
| Resting State Quantitative EEG (qEEG) Spectral Power and Theta Cordance | 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. |
| Heart-Brain Coupling (HBC): Heart Rate Oscillation Power at the Stimulation Frequency | 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. |
| EEG Microstate Temporal Parameters | 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. |
Countries
Turkey (Türkiye)
Outcome results
None listed