A Randomized, Double-Blind Controlled Comparison of NRX-101 vs. Placebo for Adults Being Treated With Robotic Transcranial Magnetic Stimulation for Treatment Resistant Depression: The SPARC-TMS Trial

18 to 65 years of age, inclusive, at Screening. 2. Participants must be initiating a new course of TMS treatment and must be TMS-naïve. 3. Able to understand and provide written and dated informed consent prior to Screening. 4. Deemed likely to comply with the study protocol, including communication of adverse events (AEs) and other clinically important information, including adherence to the text messaging component of the trial. 5. Previously diagnosed with major depressive disorder (MDD) according to the criteria defined in the DSM-5. 6. Has treatment-resistant MDD defined as failure to achieve an adequate response after at least two adequate antidepressant trials of different agents, each given at a therapeutic dose and for sufficient duration. 7. A total score ≥ 25 on the 10 items of the MADRS. 8. Has an identified reliable informant/care partner that is willing to provide information and/or supportive care as necessary. 9. If heterosexual female, a status of non-childbearing potential or use of an acceptable form of birth control per the following criteria, and agrees to continue use of the same method of birth control for the duration of study participation: 1. Non-childbearing potential: physiologically incapable of becoming pregnant (i.e., permanently sterilized \[status posthysterectomy, bilateral tubal ligation\], or post-menopausal with last menses at least one year prior to Screening); or 2. Childbearing potential, and meets the following criteria: i. Must agree to use at least one highly effective method of birth control (methods which result in a failure rate of less than 1% per year when used consistently and correctly) during study participation. Examples of acceptable highly effective methods include established use of oral, injected, implanted, or intrauterine hormonal contraception; placement of an intrauterine device or intrauterine system; or a vasectomized partner with documented azoospermia; or true sexual abstinence that is the participant's usual and preferred lifestyle. ii. Negative urinary pregnancy test at Screening, confirmed by a second negative urinary pregnancy test at Day 1, prior to receiving study treatment. 10. Body mass index (BMI) between 18-40 kg/m2; BMI up to 45 kg/m2 is allowed with Medical Monitor review and approval. 11. If receiving concurrent psychotherapy, the type and frequency of the therapy (e.g., weekly or monthly) has been stable for at least 3 months prior to Screening and will remain stable for the duration of study participation. 12. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, benzodiazepines, maximum 2 mg daily, or trazodone) will be allowed if the therapy has been stable for at least 4-weeks prior to screening and will remain stable during the course of the patient's participation in the study. 13. Concurrent treatment with benzodiazepines is allowed up to a maximum dose 2 mg/daily used for anxiety if therapy has been stable relative to dose and schedule for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the patient's participation in the study. Exclusion criteria: A patient is ineligible for inclusion in this study Heterosexual female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. 2. Female who is pregnant (positive pregnancy test at Screening) or breastfeeding. 3. Active suicidality (without the intention to act) as evidenced by a score of \>3 on the Columbia Suicide Severity Rating Scale. 4. Current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to Screening. (Note: Substance use disorder cannot be the precipitant for study entry). 5. Current DSM-5 diagnosis of alcohol use disorder 6. A lifetime history of phencyclidine (PCP)/ketamine drug abuse 7. History of schizophrenia or schizoaffective disorder 8. History of anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified (NOS), or other specified feeding and eating disorders (OSFED) within 3 years of Screening. 9. Has dementia, delirium, amnestic, or any other cognitive disorder. 10. Renal impairment defined as estimated glomerular filtration rate (eGFR) \< 60 mL/min, calculated using the 2021 CKD-EPI creatinine equation (racefree). 11. Clinically significant hepatic impairment. Clinically significant hepatic impairment is defined as a history of chronic liver disease (e.g., cirrhosis, chronic hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis) or evidence at Screening of acute liver disease or impaired liver function (e.g., ALT or AST \>3 × ULN, total bilirubin \>2 × ULN) or in the opinion of the Investigator. 12. A clinically significant abnormality on the Screening physical examination that may affect safety or study participation, or that may confound interpretation of study results according to the study clinician. 13. Risk factors for neurocardiogenic syncope including history of syncope/ presyncope related to noxious stimuli, anxiety, micturation, or posture. 14. Co-morbidities as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and electrocardiogram (ECG) which might interfere with compliance or the ability to assess efficacy or safety. 15. Diagnosis of moderate to severe heart disease or current episode of: 1. Myocardial infarction within 1 year of Screening. 2. Diagnosis of angina pectoris. 3. Prolonged QTc interval, as measured by Fridericia's correction formula (QTcF) ≥450 msec at Screening for males or ≥ 470 msec for females on 2 of 3 measurements at least 15 minutes apart prior to randomization on Day 1. 16. Diagnosis of chronic lung disease, excluding asthma. 17. Lifetime history of any of the following: neurologic conditions with structural cerebral damage, traumatic brain injury, multiple sclerosis, surgical procedures involving t