FDA Clears Clinical Trial of NRX-101 in Combination with Robotic-Enabled TMS in Patients With Depression and Suicidality

The US Food and Drug Administration cleared NRx Pharmaceuticals to initiate a clinical trial of NRX-101 (D-cycloserine/lurasidone fixed dose combination) vs placebo in patients with depression and suicidality who are being treated with either robotic-assisted transcranial magnetic stimulation (TMS) or sham TMS. The placebo-controlled phase 2/3 trial is identified as “A Randomized, Double-Blind, Three-Arm Study of NRX-101 as Adjunctive Therapy to Active or Sham Transcranial Magnetic Stimulation in Adults with Treatment Resistant Major Depressive Disorder (MIND1).”

Investigators in the randomized portion of the clinical trial will enroll 240 participants at a leading US academic teaching hospital and 3 planned study sites. Another group of participants will be enrolled at 2 United States Military Treatment Facilities. Study sites will be announced following approval by Institutional Review Boards. The trial will be conducted by a subsidiary of NRx Pharmaceuticals, NRx Defense Systems. Additionally, NRx anticipates that the MIND1 trial will be supported through nondilutive sources, given the implications of a short-term effective and noninvasive treatment for depression on force readiness within the military and first responder organizations.

Leading the clinical side of MIND1 trial is principal investigator Josh Brown, PhD, MD, who served as the principal investigator of predecessor phase 1 and phase 2 studies funded by the US Defense Advanced Research Projects Agency. In addition to serving as the NRx’s chief medical innovation officer, Brown is an assistant professor of psychiatry and the head of TMS Research at Harvard McClean Hospital.

The trial will be led organizationally by Dennis K. McBride, PhD, (CAPT, Medical Service Corps, Ret., US Navy), the president of NRx Defense Systems, a distinguished research fellow at National Defense University, and a former senior executive in the Office of the Secretary of Defense. McBride twice served as a program manager at the Defense Advanced Research Projects Agency. He has led several medically complex projects from a wide range of research and development labs and offices in the US Department of War.

“We at NRx deeply appreciate the FDA’s support for this vital research initiative that has potential to address the well-known challenge of depression and suicide within our military and first-responder organizations. A short-term treatment that has the potential to restore vital personnel to duty without disqualifying antidepressant drugs would be a major advance with implications for the entire nation,” shared McBride.

Preliminary research suggests that D-cycloserine significantly enhances the effect of TMS, with a greater than 2-fold benefit of reduction in symptoms of depression.² Subsequent nonclinical literature also demonstrates that low doses of D-cycloserine “exert a neuroplasticity effect and cause dendritic sprouting in areas of the brain associated with depression.”³ Additionally, on November 4, 2025, real world data were presented in conjunction with use of a TMS device and a 1-day TMS protocol in combination with a single administration of oral D-cycloserine. Investigators reported 87% clinical response and 72% remission at 6 weeks after a single day of treatment on the Hamilton Depression Rating Scale, with similar findings on other standard test measures.⁴

NRX-101 was awarded Breakthrough Therapy Designation by the US Food and Drug Administration for the treatment of suicidal bipolar depression in 2018, making it the first oral drug targeting this disorder.⁵ NRX-101 may represent a new class of antidepressants with the potential to decrease suicidal thoughts, as it raises levels of 2 neurotransmitters, glutamate and glutamine, whereas serotonin-based antidepressants raise serotonin levels and are associated with an increase in risk of suicide in certain vulnerable patient populations.

If the trial results are positive, D-cycloserine-augmented TMS could make a difference for first responders, those in the military, and patients with treatment-resistant depression.

References

1. NRx Pharmaceuticals (Nasdaq:NRXP) announces FDA clearance to proceed with clinical trial of NRX-101 in combination with robotic-enabled transcranial magnetic stimulation in patients with depression and suicidality. News release. May 7, 2026. Accessed May 7, 2026. https://www.globenewswire.com/news-release/2026/05/07/3289939/0/en/nrx-pharmaceuticals-nasdaq-nrxp-announces-fda-clearance-to-proceed-with-clinical-trial-of-nrx-101-in-combination-with-robotic-enabled-transcranial-magnetic-stimulation-in-patients-.html

2. Cole J, Sohn MN, Harris AD, et al. Efficacy of adjunctive D-cycloserine to intermittent theta-burst stimulation for major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2022;79(12):1153-1161. 

3. NRx Pharmaceuticals to discuss new NRX-101 pipeline indication for augmentation of transcranial magnetic stimulation. News release. December 3, 2025. Accessed May 7, 2026. https://ir.nrxpharma.com/news-releases/news-release-details/nrx-pharmaceuticals-discuss-new-nrx-101-pipeline-indication

4. Vaughn DA, Marino B, Engelbertson A, et al. Real-world effectiveness of a single-day regimen for transcranial magnetic stimulation using optimized, neuroplastogen-enhanced techniques in depression (ONE-D). 2025;5:100200.

5. NeuroRx receives FDA breakthrough therapy designation for NRX-101, first oral drug targeting suicidal bipolar depression. News release. November 13, 2018. Accessed May 7, 2026. https://www.biospace.com/neurorx-receives-fda-breakthrough-therapy-designation-for-nrx-101-first-oral-drug-targeting-suicidal-bipolar-depression