2026 ECNP Congress

PS02-2117

Real-world effectiveness of esketamine nasal spray in treatment resistant depression: results from the ECHO prospective non-interventional cohort study

Stephan Köhler — Y. Godinov, L. Häggström, A. Ibañez, V. Martiadis, C. Reif-Leonhard, J. Riise, G. Rosso, I. Turkoz, B.T. Baune · Alexianer St. Joseph Hospital Berlin-Weißensee, None, Berlin, Germany

2026 ECNP Congress

Introduction

Esketamine nasal spray (NS), in combination with an SSRI or SNRI, is approved for the treatment of patients with treatment resistant depression (TRD).[1] Given treatment goals extend beyond symptom reduction to sustained response and remission, and relapse prevention, evaluating long-term effectiveness in real-world populations remains a key consideration.

Aims

To evaluate the long-term effectiveness of esketamine NS, in combination with antidepressants, for the treatment of adults with TRD in real-world clinical settings using data from the Esketamine CoHOrt (ECHO) study.

Methods

ECHO was a prospective, non-interventional, open-label study in Belgium, Germany, Israel, Italy, Netherlands, Spain and Sweden. Esketamine NS was prescribed per local clinical practice, independent of study participation. The study included a variable-length treatment period (TP) and a 6-month post-treatment follow-up period. Clinical outcomes included Montgomery-Åsberg Depression Rating Scale (MADRS) total score and change from baseline, and remission (MADRS ≤10), response (≥50% improvement in MADRS from treatment initiation) and relapse rates (after achieving remission/response during the TP/follow-up period). Data are reported for the full analysis set up to 48 weeks of the TP.

Results

Overall, 570 patients were enrolled in the TP. Mean (standard deviation [SD]) MADRS total scores at baseline and Weeks 4, 24 and 48 were 33.3 (6.8), 23.0 (9.0), 17.6 (9.8) and 15.5 (10.0), respectively. Similar scores were observed regardless of number of previous treatment failures (Table).

The proportions of patients who achieved a clinically meaningful/substantial response (≥6-/12-point reduction in MADRS score, respectively) at Weeks 4, 24 and 48 were 68.4% (335/490)/40.2% (197/490), 83.5% (263/315)/62.9% (198/315) and 85.9% (122/142)/70.4% (100/142), respectively. Overall response rate was higher at later visits: Week 4: 22.2% (109/490); Week 24: 49.5% (156/315); Week 48: 57.0% (81/142). Remission rate was also higher at later visits: Week 4: 9.2% (45/490); Week 24: 25.7% (81/315); Week 48: 33.8% (48/142).

Among 302 patients achieving response/remission during the TP, 71 (23.5%) experienced a relapse. Mean (SD) time to first relapse was 161.2 (213.1) days. First relapses in the TP were most commonly defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (62.0% [44/71]), and by MADRS total score ≥22 (33.8% [24/71]).[2]

Conclusions

Esketamine NS resulted in clinically meaningful and sustained reductions in depressive symptoms, and higher response/remission rates at later visits. Relapse rates during the TP were low among patients who had achieved response/remission, and time to first relapse appeared relatively extended compared with previous reports.[3] The short- and long-term effectiveness of esketamine NS in real-world settings and broader patient populations reinforces clinical trial data, supporting it as a valuable therapeutic strategy for patients with TRD.

TABLE

Mean (standard deviation) MADRS total score N
Previous treatment failures
TP visit 2 3 4 ≥5
Baseline 32.8 (7.1) 158 34.2 (7.0) 150 33.0 (6.8) 112 33.0 (6.2) 150
Week 4 22.7 (9.0) 134 22.2 (8.9) 135 23.2 (10.3) 93 27.9 (7.5) 112
Week 24 18.1 (10.6) 78 17.8 (10.5) 95 17.6 (9.7) 59 16.8 (8.2) 83
Week 48 16.4 (10.6) 35 12.6 (9.4) 43 16.9 (9.5) 27 17.0 (10.0) 37

MADRS: Montgomery-Åsberg Depression Rating Scale.

References

  1. European Medicines Agency, 2019. Spravato: EPAR - Medicine overview. Available from: https://www.ema.europa.eu/en/documents/overview/spravato-epar-medicine-overview_en.pdf. [Accessed: March 2026];
  2. American Psychiatric Association, 2013. Diagnostic and statistical manual of mental disorders, fifth ed. American Psychiatric Association Publishing, Washington;
  3. Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D., Niederehe, G., Thase, M.E., Lavori, P.W., Lebowitz, B.D., McGrath, P.J., 2006. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report. American Journal of Psychiatry, 163(11), 1905-1917.