Outcomes of Intranasal Esketamine versus Intravenous Ketamine Induction Therapy

Overview

This study compares the efficacy of intranasal esketamine and intravenous ketamine for treatment-resistant depression (TRD) in a community psychiatric setting. Both treatments showed significant antidepressant effects, but no statistically significant differences were found between the two modalities.

Background

Treatment-resistant depression (TRD) is a significant clinical challenge, affecting a substantial number of patients who do not respond to conventional antidepressant therapies. Ketamine, an NMDA receptor antagonist, has emerged as a rapid-acting treatment option for TRD. Understanding the comparative effectiveness of intranasal esketamine and intravenous ketamine is crucial for optimizing treatment strategies in community psychiatric settings.

Data Highlights

Key Findings

• Both treatments resulted in significant reductions in PHQ-9 scores from baseline.
• Response rates were similar between esketamine (64.9%) and ketamine (69.2%).
• Remission rates were 32.4% for esketamine and 23.1% for ketamine.
• Induction completion rates exceeded 90% in both groups.
• One patient from each cohort discontinued due to intolerable side effects.

Clinical Implications

Both intranasal esketamine and intravenous ketamine are effective options for inducing remission in patients with TRD.

Conclusion

Both intranasal esketamine and intravenous ketamine demonstrate robust antidepressant effects in a community setting, although the lack of significant differences between the two treatments is noted.

Related Resources & Content

1. Frontiers in Psychiatry, 2026 -- Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis
2. JAMA Network Open, 2023 -- Oral Ketamine for Treatment-Resistant Depression—Not Yet Time?
3. JAMA Network Open, 2023 -- Oral Prolonged-Release Ketamine for Treatment-Resistant Depression: Two Randomized Clinical Trials
4. Frontiers in Psychiatry — Case Report: Intranasal esketamine and accelerated intermittent theta-burst stimulation for severe treatment-resistant depression with suicidal ideation
5. FDA Label for Esketamine (Spravato)
6. VA/DoD Clinical Practice Guideline for the Management of Major Depressive Disorder (MDD)
7. NICE Guideline NG222 on Depression in Adults
8. Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the use of ketamine in psychiatric practice - PubMed
9. Consensus Statement
10. S000712502400151Xjed 1..2
11. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial - PMC
12. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study - PMC
13. Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval | American Journal of Psychiatry
14. Intravenous ketamine versus esketamine for depression: a systematic review and meta-analysis
15. Frontiers | Comparative safety and tolerability of ketamine and esketamine for major depressive disorder: a systematic review and meta-analysis