On the Horizon: Intravenous Ketamine for Suicidal Depression
Trials have shown comparable efficacy to ECT in reducing suicidal thoughts.
Updated September 4, 2025 | Reviewed by Hara Estroff Marano
According to the Centers for Disease Control and Prevention, nearly 13 million individuals seriously consider suicide annually, and around 1.5 million attempt suicide. Preliminary data for 2024 indicate a potential increase in the age-adjusted suicide rate, estimated at 14.7 per 100,000 people. In the nearly two years since the launch of the 988 Suicide and Crisis Lifeline in 2022, the phone line has received more than 10 million contacts. Monthly call volume has surpassed 600,000 calls per month since early 2025.
On August 11, 2025, the U.S. Food and Drug Administration granted the designation of "fast track" in the bid for approval of NRX‑100, a preservative‑free form of intravenous ketamine, for the treatment of suicidal ideation in patients with depression , including bipolar depression. Clinical trials have shown that ketamine is highly effective for rapidly reducing suicidal thoughts.
In the past, fast-track designation has been granted based on robust data from well-controlled trials. In the case of ketamine, a Columbia University study reported that 55% of patients with suicidal ideation responded to intravenous ketamine. In French government–sponsored research, 63% of patients achieved complete remission of suicidal ideation within three days of receiving IV ketamine.
The benefits of fast-track designation include the potential for speedy approval—months instead of nearly a year. The sponsoring drug maker, NRx Pharmaceuticals, plans to submit additional clinical data, seeking accelerated approval by December 2025. If it is successful, NRX-100 would become the first FDA-approved IV ketamine for suicidal ideation in depression, a significant step toward treating this acute psychiatric crisis.
Ketamine was first approved by the FDA in 1970 for use as an anesthetic; it is often used to reduce postsurgical pain and minimize the need for opioids following surgery. Ketamine provides analgesia without causing respiratory depression, a common problem with many opioid analgesics. Ketamine also shows promise in managing some types of chronic pain, like fibromyalgia , especially when other treatments have failed. Ketamine's antidepressant and anti- anxiety effects may be particularly beneficial for individuals with chronic pain alongside depression or anxiety.
Suicide is the second leading cause of death for individuals ages 10 to 34 years. Psychiatrists often suggest treating this consequence of major depression with electroconvulsive therapy (ECT), but acute crisis management often leads to call the suicide hotline and/or seek help at an emergency room. Active suicidal thinking, an intent or a plan, usually results in referral to a psychiatric unit or hospital.
Medications for suicidal thinking might reduce the need for hospitalization or physical or chemical restraints. Clozapine is a gold-standard antipsychotic medication used for suicide risk reduction, but its use is limited to people with schizophrenia spectrum disorders. Esketamine (Spravato), a quick-acting formulation of ketamine as a nasal spray, also comes into play for suicidal ideation with major depressive disorder, but evidence for esketamine’s effect on suicide remains limited. Intravenous ketamine has been studied and is sometimes used off-label for acute suicidality , but it is not formally approved by the FDA for that indication.
Suicidal patients in the emergency room may require one-on-one staffing, need physical restraints, or be admitted to a locked psychiatric unit to prevent suicide. Ketamine offers an alternative. NRX-100 is effective for depression but is also not inferior to electroconvulsive therapy (ECT) for suicidal depression. Patients treated with ketamine have superior cognitive functioning compared to those treated with ECT, with no outcome differences. Recent findings support the short-term superiority of ketamine on cognitive functioning and the long-term cognitive safety of both ECT and ketamine for TRD.
If approved, NRX-100 could provide a fast-acting, evidence-based intervention for suicidal patients, with careful administration, monitoring, and follow-up. Ketamine has potential for abuse, addiction , and long-term safety issues. To address this issue, approval would almost certainly be tied to a Risk Evaluation and Mitigation Strategy (REMS) program, similar to safeguards in place for nasal esketamine.
Ketamine was first synthesized in 1962 and FDA-approved as an anesthetic in 1970. Esketamine received designations as fast-track and breakthrough therapy in the mid-2010s, culminating in FDA approval in March 2019 for treatment-resistant depression (TRD), later expanded to include suicidal ideation.
The form of ketamine in NRX‑100 (racemic ketamine) has been used off-label for depression in clinical settings due to rapid action (sometimes within days), especially for acute suicidality. Concerns remain about long-term effects, addictive potential, and standardized protocols.
Ketamine treatment centers in the U.S. and globally have developed a reasonably standardized approach to drug administration that could be adopted for the new agent. Relief may last days to weeks after a single infusion, but booster treatments are generally required. Continuous monitoring of vital signs (blood pressure, heart rate, oxygen saturation) is necessary. Patients must be observed for dissociation, sedation, or blood pressure spikes, during and after infusion. Patients are generally monitored for two hours post-infusion before discharge. Reduction in suicidal ideation can occur within 24 hours in many patients.
NRx Pharmaceuticals may seek accelerated approval or another expedited pathway in 2025. If approved, NRX‑100 could become the first FDA-approved IV ketamine product for suicidal ideation. Given ketamine’s use as a club drug, abuse, and addiction potential, FDA approval would also require a program for controlled administration and monitoring.
I hope ketamine IV infusion treatments will be allowed only in certified healthcare settings (hospitals, clinics, infusion centers), and not for at-home administration. Infusions must be administered and directly supervised by trained clinicians. Staff also must be able to manage acute side effects and monitor patients after infusion, likely for at least two hours before discharge. Discharge criteria would include stable vitals and orientation. In addition, patients and prescribers may need to be enrolled in a national registry, similar to the esketamine requirements.
NRX-100 will likely be distributed only through specialty pharmacies or direct-to-clinic supply channels. Packaging may use tamper-resistant vials (already part of NRx’s design) to minimize diversion risk. Counseling about risks would be needed, such as the risk for dissociation, the need for driving restrictions (no driving the same day), abuse potential, and unknown long-term effects.
If approved, IV ketamine will move beyond today’s off-label, variable protocols toward a standardized treatment available nationally for suicide and depression. REMS should enforce in-clinic use, monitoring, restricted distribution, and mandatory reporting, mirroring but likely stricter than the esketamine program due to injected ketamine’s higher abuse profile.
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NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) granted FDA Fast Track Designation for NRX-100 for suicidal ideation in patients with depression, including bipolar depression. News release. August 11, 2025. https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-inc-nasdaq…
NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) files initial section of U.S. New Drug Application to the FDA for NRX-100 (IV ketamine) for the treatment of suicidal depression. News release. December 30, 2024. https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-inc-nasdaq…
FDA to issue new commissioner’s national priority vouchers to companies supporting U.S. national interests. Press release. June 17, 2025. Accessed August 11, 2025. https://www.fda.gov/news-events/press-announcements/fda-issue-new-commi…
NRx Pharmaceuticals, Inc. (NASDAQ:NRXP) announces filing of commissioner's national priority voucher application for intravenous ketamine (NRX-100). Press release. June 23, 2025. Accessed August 11, 2025. https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-inc-nasdaq…
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Mark S. Gold, M.D., is a pioneering researcher, professor, and chairman of psychiatry at Yale, the University of Florida, and Washington University in St Louis.
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