Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
tms, eeg
Brief summary
This study tests whether a brain stimulation treatment for depression called intermittent theta burst stimulation (iTBS) can be improved by tailoring it to each individual. A type of brain signal measured with electroencephalography (EEG) after a single pulse of brain stimulation, called an early local TMS-evoked potential (EL-TEP), is used to identify which stimulation settings work best for each participant. The investigators will compare individualized (personalized) iTBS settings to standard (non-personalized) settings and to inactive (sham) stimulation. Participants are adults with treatment-resistant depression.
Interventions
DEVICEPersonalized iTBS
Intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex using individualized pulse count (600, 1200, or 1800 pulses) and intensity (90% or 120% rMT) determined by EL-TEP screening.
DEVICENon-Personalized iTBS
Intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex at fixed parameters: 1800 pulses, 120% resting motor threshold.
DEVICESham iTBS
Inactive sham stimulation using a shielded coil with electrical scalp stimulation to mimic sensory experience of active iTBS.
Sponsors
Stanford University
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
All participants receive all three arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18-65 years * Clinical diagnosis of Major Depressive Disorder (MDD), confirmed by structured clinical interview * Current moderate-to-severe depressive episode (MADRS score ≥ 20) * Moderate-to-severe treatment resistance, assessed using the Maudsley Staging Method * Able to comprehend English sufficiently to complete study procedures and assessments * Able to maintain stable antidepressant regimen or remain medication-free for at least 4 weeks prior to and during the study
Exclusion criteria
* Primary psychiatric diagnosis other than MDD * Contraindications to MRI (e.g., implanted metal) * Conditions or medications that may increase risk associated with TMS * Prior exposure to repetitive TMS (rTMS) * Non-response to electroconvulsive therapy (ECT) * History of psychosurgery for depression * High suicidal risk as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Early Local TMS-Evoked Potential (EL-TEP) Amplitude | Baseline, end of 10 iTBS sessions within a single testing day (10 hours) | EL-TEP amplitude is the peak-to-trough amplitude of the early (20-60 ms) EEG response recorded over the left dorsolateral prefrontal cortex following single TMS pulses. Percent change is calculated from pre-iTBS to post-iTBS for each stimulation condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute EL-TEP Suppression Following Each Screened iTBS Condition | Baseline, end of each iTBS session during the screening phase (3 screening days, up to approximately 3 weeks) | Percent change in EL-TEP amplitude from before to after each of the six screened iTBS parameter combinations during the screening phase. |
| Trajectory of EL-TEP Change Across Multiple Sessions Within a Testing Day | Baseline, before and after sessions 1, 2, 3, and 10 within a single testing day (10 hours) | EL-TEP amplitude measured before and after sessions 1, 2, 3, and 10 on each testing day to characterize cumulative effects. |
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score | Baseline, end of each testing day (up to approximately 7 weeks) | Clinician-administered scale assessing depressive symptom severity. Score range: 0-60 (higher scores indicate greater severity). |
| Change in Quick Inventory of Depressive Symptomatology (QIDS) Score | Baseline, end of each testing day (up to approximately 7 weeks) | Self-report measure of depressive symptom severity. Score range: 0-27 (higher scores indicate greater severity). |
| Change in Generalized Anxiety Disorder 7-Item Scale (GAD-7) Score | Baseline, end of each testing day (up to approximately 7 weeks) | Self-report measure of anxiety symptom severity. Score range: 0-21 (higher scores indicate greater severity). |
| Change in N-Back Task Performance | Baseline, end of each testing day (up to approximately 7 weeks) | Working memory performance assessed using the N-back task. Outcome is accuracy and reaction time. |
| Change in Multi-Source Interference Task (MSIT) Performance | Baseline, end of each testing day (up to approximately 7 weeks) | Executive function assessed using the MSIT. Outcome is accuracy and reaction time. |
| Change in Affective Processing Task Performance | Baseline, end of each testing day (up to approximately 7 weeks) | Emotional face recognition task performance. Outcome is accuracy. |
Countries
United States
Contacts
CONTACTJade T Truong, BS
PRINCIPAL_INVESTIGATORCorey J Keller, MD, PhD
Stanford University
Outcome results
None listed