Adding D‑serine to TMS treatment for depression

Pharmacologic Augmentation of TMS for Depression With D-serine

This trial tests whether taking D‑serine along with transcranial magnetic stimulation (TMS) helps adults with major depressive disorder feel better compared with TMS plus a placebo.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Mclean Hospital (Academic / other)
• Locations: 1 site (Belmont, Massachusetts)
• Trial ID: NCT06876129 on ClinicalTrials.gov

What this trial studies

This Phase 1 interventional trial tests whether the NMDA co‑agonist D‑serine given alongside repeated TMS sessions improves clinical outcomes in adults with major depressive disorder. Participants receive a course of TMS using intermittent theta-burst (iTBS) or an 18‑Hz protocol across approximately 30 sessions while taking D‑serine or a placebo, with clinical measures collected at admission, interim points, and discharge. Symptom outcomes are captured using McLean Hospital's Clinical Measurement Initiative (CMI) via validated questionnaires including the QIDS‑SR, PHQ‑9, and GAD‑7 entered into REDCap. Safety screening excludes people with seizure history, implanted metal/devices, significant substance use that raises seizure risk, pre-existing renal disease, pregnancy or breastfeeding, and those taking interacting medications.

Who should consider this trial

Good fit: Adults aged 18–80 with a clinical diagnosis of major depressive disorder who are English-speaking, can swallow capsules, and pass TMS safety and medication-interaction screening are ideal candidates.

Not a fit: Patients with pre-existing renal disease, known allergy to D‑serine, taking medications with known interactions, pregnant or breastfeeding people, children, or those with seizure history or incompatible implants are unlikely to be eligible or to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, adding D‑serine could increase the effectiveness of TMS and lead to larger or faster reductions in depressive symptoms.

How similar studies have performed: Combining NMDA-targeting drugs like D‑serine with TMS is a relatively novel approach with limited clinical data so far, although early research on NMDA modulation suggests potential effects on antidepressant response.

Eligibility criteria

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.

Where this trial is running

Belmont, Massachusetts

• McLean Hospital — Belmont, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Joshua C Brown, MD, PhD

Conditions Depression