Comprehensive Systematic Review of Esketamine Nasal Spray as a Standalone Rapid-Acting Treatment for Treatment-Resistant Depression: Integrating Clinical Trial Data and Emerging Real-World Evidence on Efficacy, Safety, And Relapse Prevention
Angelin Grace Thomas, Dhivyaprasath Palaniappan, Sagar Guruswamy, Amritha Chandrasekaran Sashikar
International Journal of Drug Delivery Technology June 30, 2026 DOI: 10.25258/ijddt.16.59s.166 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | People with treatment-resistant depression |
| Intervention | Esketamine nasal spray |
| Topics | Depression Ketamine Esketamine |
| Keywords | Nasal spray Clinical trial Placebo Depression economics Relapse prevention Dose Intensive care medicine Medline Adverse effect Depressive symptoms Randomized controlled trial Psychological intervention |
| Key findings | Esketamine reduces depressive symptoms more effectively than placebo or quetiapine, with rapid onset and mild-to-moderate side effects. |
Abstract
Major depressive disorder, or MDD, is a common cause of disability around the world. Treatment-resistant depression, or TRD, is a tough challenge. Many people do not respond well to treatment, which increases the risk of relapse and suicide. Esketamine is a new treatment that comes as a nasal spray. It works quickly and targets a specific brain receptor. This review looks at research from trials and real-world studies to see how well esketamine works, how safe it is, and if it helps prevent relapse when used alone.Research shows that esketamine reduces depressive symptoms more effectively than a placebo and other treatments like quetiapine. Many patients felt better within days, and some benefits lasted for weeks or even months after stopping treatment. Most side effects, like dizziness, nausea, and changes in blood pressure, were mild to moderate. These effects usually went away within two hours after taking the drug. There were no serious side effects or deaths reported. Also, gathering patient feedback during treatment helped doctors create better care plans.Some studies had small sample sizes, and there was not much information on long-term effects beyond 12 months. Still, the evidence suggests that esketamine is a fast-acting, effective, and mostly safe treatment for TRD. Ongoing phase 3 studies will help understand the best dosages and long-term results. Esketamine is an important step forward for patients who struggle with treatmentresistant depression.
Comparable studies
Other narrative reviews on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |