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

Esketamine nasal spray reduces depressive symptoms more effectively than a placebo or other treatments like quetiapine for people with treatment-resistant depression. Many patients felt better within days, and some benefits lasted weeks or months after stopping treatment. Most side effects, such as dizziness, nausea, and blood pressure changes, were mild to moderate and resolved within two hours. No serious side effects or deaths were reported. Gathering patient feedback during treatment helped doctors create better care plans. Some studies had small sample sizes, and long-term effects beyond 12 months are not well documented. Ongoing phase 3 studies aim to clarify optimal dosages and long-term outcomes.

Study at a glance

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.