Pharmacologic Augmentation of TMS for Depression With D-serine

DEVICE

TMS

Subjects will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device plus placebo.

DRUG

D-serine

D-serine, 80 mg/kg, oral administration, will be advised to be taken 1-hour prior rTMS treatment day (Mon-Fri) for 6 weeks. Dosing is based on maximal plasticity at 80 mg/kg, and clinical dose-finding studies demonstrating that doses between 60 - 120 mg/kg were superior in clinical effectiveness to 30 mg/kg and were safe. Subjects will not be randomized into their TMS group and will either receive iTBS using a Magventure TMS device or 18-Hz H1 TMS using a dTMS Brainsway device. Subjects will have their TMS protocol/treatment determined at the time of consultation according to clinical appropriateness as is the standard of care at the TMS clinic at McLean Hospital.

OTHER

Placebo

The placebo is an inactive substance (e.g., lactose or cellulose) packaged to be identical in appearance, taste, and smell to the active study drug. Oral administration, will be advised to be taken 1-hour prior rTMS treatment day (Mon-Fri) for 6 weeks.

Patient Health Questionnaire 9 (PHQ-9)

Time frame: Through TMS treatment course, average of 6-8 weeks; taken at treatment #1, #9, #14, #19, #24, #29, and #34, an average of once per week

The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 test evaluates several factors that revolve around the criteria used to professionally diagnose depression under the current DSM-5. The total score is calculated and can range from zero to 27, with 27 being the highest and indicative of the worst outcome/severity. * A score of 20 or higher indicates that severe major depression * Scoring between 15 and 19 suggests that there is possibly moderately severe major depression * Scoring between 10 and 14 means that you may have a moderate severity depression * A score between 5 and 9 reveals that mild symptoms of depression appear to exist

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.