NRx Pharmaceuticals presented real‑world evidence at ASCP 2026 showing intravenous ketamine achieved higher remission and response rates than intranasal esketamine in major depressive disorder, underscoring regulatory interest in real‑world data for treatment‑resistant depression.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
NRx Pharmaceuticals presented new real‑world evidence at the 2026 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting showing that intravenous (IV) ketamine achieved higher remission and response rates than intranasal esketamine in adults with major depressive disorder (MDD).
The peer‑reviewed poster, authored by researchers from Osmind and Yale University, analyzed outcomes from more than 10,000 patients treated across approximately 800 community psychiatry clinics in the United States.
Clinical Context: Treatment‑Resistant Depression
Treatment‑resistant depression (TRD) remains a major challenge, with many patients failing to achieve adequate symptom control despite multiple therapies. Ketamine, an NMDA receptor antagonist, has emerged as a rapidly acting antidepressant capable of producing symptom improvement within hours to days.
Esketamine, the S‑enantiomer of ketamine, is the only FDA‑approved intranasal therapy for TRD and MDD with acute suicidal ideation or behavior. Comparative effectiveness data from routine practice have been limited until now.
Study Design and Patient Cohort
Researchers evaluated de‑identified electronic health record data from 8,224 patients treated with IV ketamine and 1,830 patients treated with intranasal esketamine. Matching on baseline characteristics produced a comparative cohort of 3,560 individuals. Depression outcomes were assessed using the Patient Health Questionnaire‑9 (PHQ‑9), a validated measure of depressive symptom severity.
Clinical Outcomes: Higher Remission with IV Ketamine
Both therapies produced meaningful and sustained reductions in depressive symptoms. Among matched patients, 34% of those receiving IV ketamine achieved remission compared with 26% of patients treated with intranasal esketamine. Response rates reached 63% in the IV ketamine group versus 58% in the esketamine group. Statistical analysis showed that IV ketamine patients were 22% more likely to achieve treatment response (OR 1.22; P<0.003) and approximately 50% more likely to achieve remission (OR 1.51; P<0.001).
Limitations and Interpretive Caution
Investigators cautioned that treatment allocation was not randomized, raising the possibility of unmeasured confounding. They also noted that the cohort was limited to clinics using the Osmind platform, which may not fully represent the broader population of patients receiving ketamine‑based therapies nationwide. Despite these limitations, the findings highlight the potential clinical significance of IV ketamine’s higher remission rates in TRD.
Regulatory and Policy Relevance
The results arrive amid growing interest in the role of real‑world evidence in regulatory decision‑making for psychiatric therapies. Recent federal initiatives, including a White House Executive Order and congressional appropriations language, have emphasized the importance of real‑world data in evaluating treatments for depression and suicidality. Esketamine remains the only FDA‑approved ketamine‑based therapy, underscoring the potential implications if IV ketamine’s real‑world advantages are confirmed in prospective studies.
Corporate Perspective and Next Steps
NRx Chairman and CEO Dr. Jonathan Javitt welcomed the rigor of the analysis and noted alignment with discussions held during a recent FDA Type C meeting regarding the role of real‑world evidence in depression therapy development. He emphasized the need for larger confirmatory studies to determine whether the observed advantages of IV ketamine translate into broader clinical practice and future regulatory pathways.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.