Synaptic Mechanisms of Continuous Theta Burst Stimulation in Depression (NCT07560878)
🩺 Plain-English Summary (8th-Grade Level)
Many people with depression do not get better with standard treatments like medication. One promising alternative is transcranial magnetic stimulation (TMS), a non-invasive procedure that uses magnetic pulses to stimulate specific brain regions. A particular pattern of TMS called continuous theta-burst stimulation (cTBS) is thought to reduce overactive brain activity in depression, but the investigators do not yet fully understand how it works at the level of brain cells and connections. This study aims to determine the biological mechanism by which cTBS changes brain activity in people with depression. Specifically, the investigators are testing two competing ideas: (1) that cTBS works by weakening the connections between brain cells through a process called long-term depression (LTD), which is driven by a chemical messenger system called glutamate; or (2) that cTBS works by increasing the brain's natural "braking" system, driven by a different chemical messenger called GABA. To test these ideas, participants with depression will receive cTBS along with one of four FDA-approved medications, or placebo, that either boost or block these chemical messenger systems. The investigators will measure changes in brain activity using electroencephalography (EEG) recorded simultaneously with TMS. Specific patterns in the EEG signal, called TMS-evoked potentials (TEPs), act as a window into how different brain cell types are responding to stimulation. Each participant will complete four study visits, each testing a different drug-TMS combination in random order. One group of participants will test drugs targeting the glutamate system (d-cycloserine and memantine). A second group will test drugs targeting the GABA system (lorazepam and baclofen). All drugs are given as a single oral dose and are commonly used in clinical practice. Understanding exactly how cTBS works at a biological level could open the door to more effective, personalized TMS treatments.
Who can join: To join this study, participants generally need to meet the listed inclusion criteria (5 items) and avoid the listed exclusions (11 items).
Location: McLean Hospital — Belmont, Massachusetts
Age range: 18 Years
🧪 Interventions in This Study
📋 "Do I Qualify?" — 1-Minute Self Screener
Instant ChecklistCheck every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).
Usually NOT eligible if any of the following apply:
- 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
🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.
📍 All Participating Trial Locations (1 Sites)
- McLean Hospital — Belmont, Massachusetts
📞 Contact the Study Coordinator
Phone: (617) 855-2153
Email: pganesh@mgb.org
Coordinator details come directly from the registered NIH protocol. Confirm the study is still recruiting before traveling.
💰 Cost, Insurance & Patient Rights
- 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
- Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
- Voluntary Participation: You may withdraw at any time without affecting your standard medical care.
More studies in Major Depression
- Leucine in Midlife Depression — Atlanta, Georgia
- Characterizing Cognitive Decline in Late Life Depression: The ADNI Depression Project — San Francisco, California
- Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression — Birmingham, Alabama
- RCT of At-Home tDCS for Depression in Pregnancy — Toronto, Ontario
- Accelerated High-Dose tDCS for Depression — Charleston, South Carolina
Explore by condition: All Major Depression clinical trials
💡 How to Participate
- Check the checklist above to see if you may qualify.
- Contact the study coordinator using the phone/email above.
- Ask about the visit schedule, what is covered at no cost, and any travel support.
- Confirm with your own doctor before making a decision.