Single Day of Ultra-accelerated TMS With a Single Dose of NRX-101

In this pilot study, investigators aim to combine D-cycloserine, lurasidone, and single-day repeated intermittent Theta Burst Stimulation (iTBS) to preliminarily assess clinical improvement in an open-label cohort and monitor for adverse events over a 6-week follow-up period.

Inclusion Criteria: * Male or Female adults (+18 years old) * from any ethnic or racial background * with moderate to severe depression, as indicated by scores of: ≥ 20 on the MADRS; AND ≥ 10 on PHQ-9. Exclusion Criteria: * History of manic or hypomanic symptoms; * lifetime DSM-5 psychotic spectrum disorder or current clinically significant psychotic symptoms; * active alcohol or substance use disorder that, in the opinion of a study physician/PI, is of sufficient severity to impede engagement in treatment or is associated with significant risk of medical withdrawal; * anorexia nervosa or eating disorder not otherwise specified that, in the opinion of a study physician/PI, is of sufficient severity to be associated with significant medical risks; * current suicide risk sufficient to require immediate hospitalization (C-SSRS 4 or above) * history of traumatic brain injury (TBI) that, in the opinion of a study physician/PI, would significantly increase risk of seizure; * any other significant neurological disorder likely to increase risk of seizure, in the opinion of a study physician/PI; * diagnosed neurodevelopmental disorder (e.g., autism, Down syndrome; Ehlers-Danlos Syndrome); * current diagnosis of delirium or greater than mild dementia; * cognitive disorder secondary to a general medical condition suggesting probable TBI or intellectual impairment; * Pregnant and breastfeeding women are not eligible to participate in this study excluded in line with prior work using DCS and TMS (Rossi et al., 2021). To confirm eligibility, all female participants of childbearing potential will be required to undergo a urine pregnancy test prior to enrollment. Additionally, if at any point during the study the participant or the researcher suspects that the participant may have become pregnant, a urine pregnancy test will be administered to ensure continued eligibility; * Participants with contraindications to TMS (e.g., metal in head or neck area), or at increased risk for adverse events (e.g., seizure history or markedly heightened risk factors for seizures, serious medical problems, implanted devices) will be excluded; * Participants with a known allergy to DCS or LRD will be excluded; * fMRI contraindications follow those of TMS and individuals unable to safely receive either will be excluded; * No healthy volunteers will be recruited; * No patients with involuntary hospitalization status will be recruited.