Suicide persists as a leading cause of death in the United States, with rates climbing steadily over the last two decades, rising nearly 37% between 2000 and 2022. Recent data from the U.S. Centers for Disease Control and Prevention (CDC) shows that someone takes their life every 11 minutes.
Decades of research have established ties between suicidal ideation and multiple mental health disorders, including major depressive disorder, bipolar depression, and substance use disorder. The numbers are staggering. In 2022 alone:
- 13.2 million Americans seriously considered suicide.
- 3.8 million planned for it.
- And 1.6 million people attempted it.
Worse still, 49,476 people succeeded in taking their own lives in 2022. It was enough to secure its spot as the country’s 11th leading cause of death.
Despite this, there isn’t a single FDA-approved pharmacotherapy on the market today for acute suicidal crises. Electroconvulsive therapy (ECT) and inpatient psychiatric care remain the only FDA-approved treatments for curbing suicidal ideation in patients with both major depressive and bipolar disorders.
That’s where NRX-100 comes in.
What Is NRX-100?
NRX-100 is a proprietary preservative-free formulation of IV ketamine that the company submitted to regulators as a treatment for acute suicidal crises in certain types of depression.
NRx Pharmaceuticals developed NRX-100 as a safe, potentially patentable formulation of IV ketamine. The firm’s researchers designed NRX-100 to have fewer adverse effects than available generic formulations of IV ketamine. It also features no potentially toxic preservatives and includes diversion-resistant packaging.
Ketamine is an anesthetic agent that caregivers can prescribe off-label as an adjunct to treat acute suicidal crises in depression. Although IV ketamine still hasn’t earned regulatory approval to treat acute suicidality, most consider it a standard of care for acute suicidal ideation associated with bipolar depression. Peer-reviewed studies – as well as widespread clinical evidence – have supported its off-label use for this purpose.
Researchers have argued that ketamine’s antidepressant effects work through the brain’s N-methyl D-aspartate (NMDA) receptors. But these effects are short-lived and require repeated infusions. This makes ketamine suitable (primarily) for acute cases of suicidal crises.
How Does It Treat Suicidality?
The data has established a link between the brain’s NMDA receptors and the regulation of the excitatory neurotransmitter glutamate. Researchers have long tied these receptors to the pathophysiology of depression.
Research is still ongoing concerning the role of these receptors in depression, as well as suicidal ideation associated with depressive disorders. But they’ve already made several critical observations that support its involvement in the pathogenesis of depression and acute suicidality. For example:
- Researchers have observed dysfunction in NMDA receptors and glutamate levels in conjunction with several mood disorders.
- Drugs that modulate this receptor showed positive therapeutic benefits. This includes conventional mood stabilizers/antidepressants, as well as non-conventional agents such as ketamine.
- Various studies showed that ketamine caused a statistically significant decrease in depressive symptoms and acute suicidality, especially in the short term.
From Clinical Trials to NDA Application
NRX-100’s pioneering journey began with its application for Fast Track designation. This allowed it to be part of an clinical trial exploring the use of NRX-101, a fixed-dose combination of D-cycloserine and lurasidone, as a treatment for suicidal treatment-resistant bipolar depression, including patients with akathisia.
Researchers used IV ketamine as an initial stabilization agent before a six-week course of NRX-101, which showed promising results in maintaining improvement in depression and reducing suicidal ideation. Patients also reported fewer side effects.
As a result, the U.S. Food and Drug Administration (FDA) suggested that NRx file an Investigational New Drug (IND) application seeking New Drug Approval (NDA) using data obtained from the NRX-101 clinical trials, along with data pulled from multiple European studies.
Regulatory Status
NRX-100 earned the FDA’s Fast Track designation in 2017 for use as part of a sequential treatment protocol in combination with NRX-101 (D-cycloserine/lurasidone) for the treatment of suicidal bipolar depression.
In December 2024, NRX Pharmaceuticals initiated filing of a New Drug Application (NDA) for NRX-100 with the FDA seeking to offer the molecule as a first-mover in the treatment of suicidal bipolar depression, as well as suicidal ideation in major depressive disorder and other forms of depression.
The company made this move based on data from clinical trials that support the medicine’s effectiveness, as well as the lack of an FDA-approved drug for this unmet medical need. Experts project strong growth in the anti-suicide drug market, forecasting a market value of nearly $5 billion by 2026.
Bottom Line
While suicide rates continue to climb without an FDA-approved pharmacotherapy for acute suicidal crises, millions remain desperate for options. NRX-100 represents a critical step forward. By leveraging IV ketamine’s rapid-acting antidepressant effects in a safer, preservative-free formulation, it has the potential to plug a crucial gap in suicide prevention.
Its development, regulatory progress, and promising clinical data offer new hope to millions of Americans struggling with acute suicidality. It also marks a milestone in the fight against one of the nation’s most urgent public health crises.
Further Reading
How NRx Could Upend the Fight Against Depression and Suicide
