How patterned magnetic pulses (cTBS) change brain wiring in depression
Synaptic Mechanisms of Continuous Theta Burst Stimulation in Depression
This study tests whether a patterned magnetic brain stimulation called continuous theta-burst stimulation (cTBS), with and without short-acting drugs, changes synaptic signaling and brain responses in people with major depression.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 80 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Mclean Hospital Academic / other |
| Locations | 1 site (Belmont, Massachusetts) |
| Trial ID | NCT07560878 on ClinicalTrials.gov |
What this trial studies
This early-phase trial uses transcranial magnetic stimulation combined with EEG (TMS-EEG) and pharmacologic probes to probe how cTBS alters synaptic function in people with moderate to severe major depressive disorder. Investigators compare two mechanistic hypotheses: that cTBS produces long-term depression (LTD)-like weakening of glutamatergic synapses, or that it increases GABAergic inhibition. The protocol uses drug challenges (D-cycloserine, memantine, lorazepam) and a sham TMS condition to isolate neurotransmitter-specific effects while recording cortical responses. Results will map drug-modulated TMS-EEG signatures to infer synaptic mechanisms that underlie cTBS effects in depression.
Who should consider this trial
Good fit: Ideal candidates are adults with moderate to severe major depressive disorder who are on a stable medication regimen, have no contraindications to TMS or the study drugs, and are not currently receiving TMS, ECT, or ketamine.
Not a fit: People with a history of seizures, major neurological or intracranial pathology, unstable medications, active high-risk suicidality, or inability to tolerate TMS are unlikely to benefit or to be eligible.
Why it matters
Potential benefit: If successful, the results could help tailor cTBS protocols and drug combinations to make brain stimulation more effective and predictable for people with depression.
How similar studies have performed: Prior human motor-cortex studies have shown that NMDAR antagonists can block cTBS-induced inhibition, supporting an NMDA/glutamate role, while direct tests of GABAergic contributions to cTBS in depression remain limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Can safely receive TMS and study drugs * Stable medication regimen for one month prior to study participation, and for the duration of the study * Not currently receiving TMS, ECT, or ketamine * No active safety concerns related to suicidality * Moderate to severe Major Depressive Disorder as indicated by the Patient Health Questionnaire or Quick Inventory of Depressive Symptomatology Exclusion Criteria: * History of seizures or epilepsy * History of intracranial pathology or lesions from any etiology * History of traumatic brain injury including prolonged loss of consciousness more than 15 min * Signs of increased intracranial pressure * Any major neurological conditions (ex: recent stroke, tumor, neurodegenerative disorders, etc.) * Major medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) * Severe migraines that may result in treatment intolerance. * Inability to tolerate MRI. * Pregnancy * Known allergic reaction to d-cycloserine, baclofen, memantine, or lorazepam
Where this trial is running
Belmont, Massachusetts
- McLean Hospital — Belmont, Massachusetts, United States (Recruiting)
Study contacts
- Principal investigator: Joshua C Brown, MD, PhD — Mclean Hospital
- Study coordinator: Prem Ganesh, MS
- Email: pganesh@mgb.org
- Phone: 617-855-2153
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.