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Pharmacologic Augmentation of TMS for Depression With D-serine

The goal of this study is to test whether combining D-serine with 30 treatments of a) iTBS and b) 18-Hz protocols will enhance clinical outcomes compared to rTMS with placebo (i.e., sugar pill). The investigators hypothesize that NMDA receptor activation via D-serine combined with repeated sessions of rTMS will produce greater clinical outcomes than iTBS with placebo and 18-Hz with placebo.

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ClinicalTrials.gov IDNCT06876129

PhasePHASE1

Enrollment60

SponsorMclean Hospital

Age18 Years – 80 Years

SexALL

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Conditions studied

Depression

About this study

Interventions

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.

Primary outcomes

Patient Health Questionnaire 9 (PHQ-9) (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)

Eligibility information

Inclusion Criteria: * Clinical diagnosis of MDD * English-speaking * Adults aged 18-80 * Must be able to swallow capsules Relative contraindications/possible exclusion criteria: * Containing any implanted metal or devices * Current or previous seizure history * Active substance use that may significantly alter the seizure threshold Any further safety clearances, and outpatient consultation opinions that are necessitated based on the answers to the screening will be obtained prior to moving forward with the study, as an already established practice within the clinic practice. In addition, any relative contraindications will be further reviewed according to Rossi et al.'s most updated safety guidelines for TMS. Exclusion Criteria: * Patients with pre-existing renal disease * Known allergy to D-serine, or with * Patients taking medications with known drug-drug interactions * Children * Pregnant or breast-feeding women The investigators will not include children because prior safety and dosing studies excluded children. Although considered safe for TMS, the investigators will not include pregnant or breast-feeding women on the basis of unknown safety profile of exogenous D-serine for these patients.

Study locations

McLean Hospital, Belmont, Massachusetts 02478 United States

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-11-06.