Esketamine Nasal Spray Shows Rapid, Durable Effectiveness in Treatment-Resistant Depression

New real-world evidence on esketamine (Spravato; Janssen Pharmaceutical) nasal spray is reinforcing its role as an effective and durable treatment option for adults with treatment-resistant depression (TRD), offering clinically meaningful symptom improvement outside the controlled environment of randomized trials.¹

“These results reinforce esketamine nasal spray as an effective option for adults with treatment-resistant depression, many of whom have spent too long cycling through treatments that don’t meaningfully improve their symptoms,” said Christine Reif-Leonhard, MD, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt – Goethe University Frankfurt, Frankfurt am Main, Germany, in a statement. “The essential real-world insights gained from the ECHO study complement existing randomized clinical trial findings, further guiding clinical practice and allowing us to optimize personalized treatment pathways for our patients with treatment-resistant depression.”

TRD remains a significant clinical challenge, affecting a substantial proportion of patients with major depressive disorder who fail to respond to at least 2 prior antidepressant therapies. These patients often experience prolonged disease burden, functional impairment, and increased risk of relapse, underscoring the need for therapies that act rapidly and sustain long-term benefit.

Previously, esketamine demonstrated relatively strong and consistent outcomes compared with other antidepressant modalities, particularly in control group performance. In one analysis, control group response rates in esketamine studies reached approximately 42%, notably higher than those observed in selective serotonin reuptake inhibitor trials (33%) and substantially higher than in psilocybin trials (19%).²

Esketamine’s mechanism of action also distinguishes it from conventional antidepressants. As a glutamatergic modulator, it targets pathways different from monoaminergic agents, offering a novel approach for patients who have not benefited from traditional therapies.¹ This innovation has positioned esketamine as a key advancement in the evolving treatment landscape for depression.

The latest findings draw from real-world data evaluating the effectiveness of esketamine nasal spray in routine clinical practice.

In a cohort spanning Europe and Israel, 570 patients initiated treatment with esketamine during a variable treatment period, with a mean (SD) duration of 9 months, with 301 patients continuing into a 6-month post-treatment follow-up. Treatment was associated with statistically significant and clinically meaningful reductions in depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Mean scores improved by –10.3 points (95% CI, –11.1 to –9.5; P < .001) at week 4, –14.4 points (95% CI, –15.4 to –13.5; P < .001) at week 12, and –17.6 points (95% CI, –19.4 to –15.8; P <.001) by week 48, demonstrating both rapid onset and sustained symptom improvement over time.

Furthermore, MARDS scores remained stable after discontinuing treatment, with a mean change of –1.4 points from baseline to week 24.

“The ECHO study is unique in that, for the first time, we have evaluated the durability of effect in real-world practice after stopping esketamine nasal spray treatment in patients with treatment-resistant depression,” said Tamara Werner-Kiechle, MD, therapeutic area head, neuroscience, cardiopulmonary and early portfolio, Europe, Middle East & Africa, Johnson & Johnson, in a statement. “We were thrilled to see sustained symptom stability across the 6-month follow-up period. Creating respite from severe depressive symptoms that lasts beyond the immediate treatment period will significantly improve the lives of people affected, both directly and indirectly, by this devastating disease.”

References

1. New Spravato (esketamine nasal spray) data support robust effectiveness and show durable effect for treatment resistant depression in a real-world setting. News release. Johnson & Johnson. March 28, 2026. Accessed April 1, 2026. https://www.jnj.com/innovativemedicine/emea/media-center/press-releases/new-spravato-esketamine-nasal-spray-data-support-robust-effectiveness-and-show-durable-effect-for-treatment-resistant-depression-in-a-real-world-setting

2. Hippensteele A. Reassessing antidepressant efficacy: a meta-analysis of control group outcomes in SSRI, psilocybin, and esketamine trials. AJMC^®. July 31, 2025. Accessed April 1, 2026. https://www.ajmc.com/view/reassessing-antidepressant-efficacy-a-meta-analysis-of-control-group-outcomes-in-ssri-psilocybin-and-esketamine-trials