Phase 3 N=28 Randomized Quadruple-blind Treatment

EEG Synchronized TMS Trial for Depression

Depression

Bottom Line

View on ClinicalTrials.gov: NCT03421808 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Aug 2025

Primary outcome: Primary: Remission Rate — 2; 3 Participants — p=0.6

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Transcranial Magnetic Stimulation (TMS) (Device)
Age: Adult, Older Adult · 21+ yrs
Sex: All
Sponsor: Medical University of South Carolina
Primary completion: Jan 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Remission Rate	2; 3	0.6
SECONDARY Number of Participants With EEG Phase Synchronization Frequency Changes	3; 1	—
SECONDARY EEG-TMS-fMRI Bold Changes in Cingulate Cortex	—	—

Summary

Daily prefrontal TMS for depression, as developed by the PI, involves delivering TMS pulses to the prefrontal cortex and not assessing what the actual EEG phase is of the person's brain. In cardiology, in order to stimulate the heart effectively, one has to know the rhythm and phase of the heartbeat in order to perform cardioversion. The investigators wonder if it is important to time the brain stimulation with the phase of the person's brain. The brain has definite rhythms, and cycles through being excited or resting. A common EEG rhythm is alpha frequency. Theoretically, the effect of the TMS pulse might be diminished if it was delivered when the brain was temporarily cycling into an off state. In the r21 part of this grant, the investigators designed and constructed a combined TMS/EEG/fMRI system. With that equipment the investigators found that TMS pulses have different effects deeper in the brain as a function of the EEG alpha phase. Pulses delivered during a rising phase produce larger blood flow changes deeper in the brain than do pulses delivered during a falling phase. In the R33 phase of the grant the investigators now take that idea into a small clinical trial in depression to test if synchronized pulses have a larger clinical effect than do non-synchronized pulses.

Eligibility Criteria

Inclusion Criteria

Diagnosis of unipolar major depressive disorder, in a current major depressive episode, without psychotic features
Pretreatment Hamilton score ≥ 20
Age between 21 and 70 years
Fixed and stable antidepressant medications for 3 weeks prior and during the rTMS trial. Limit on benzodiazapenes to lorazepam (or equivalent) up to 3 mg every day
Moderate level of resistance to antidepressant treatment in the current episode, defined as failure of 1-4 adequate medication trials or intolerance to at least 3 trials, and duration of current episode ≤ 3 years
No history of schizophrenia, schizoaffective disorder, other [non mood disorder] psychosis, depression secondary to a medical condition, mental retardation, substance dependence or abuse within the past year (except nicotine), bipolar disorder, psychotic features in this or previous episodes, amnestic disorder, dementia or MMSE ≤24, delirium, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder
No current Vagus Nerve Stimulation
No history of failing to respond to an adequate course of ECT in this or any episode, and no ECT within the past 3 months
No contraindication to MRI
No contraindication to rTMS (history of neurological disorder or seizure (except induced by ECT), increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for >15 minutes, implanted electronic device, metal in the head, or pregnancy)
No history of autoimmune, endocrine, viral, or vascular disorder. No unstable cardiac disease, uncontrolled hypertension, or sleep apnea
No active suicidal intent or plan, or history of attempt within the past 12 months
Willing to provide informed consent

Exclusion Criteria

To ensure that baseline levels of depression severity are stable at the time of study enrollment, patients will be dropped if they show > 30% improvement in the HRSD score from the time of initial intake (e.g., screening) to the baseline assessment.
Patients must have a recordable alpha frequency.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03421808). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.