2026 ECNP Congress

PS03-3128

Real-world effectiveness and treatment duration by psychiatric comorbidity status: esketamine nasal spray for treatment-resistant depression

Vassilis Martiadis — B.T. Baune, K. Feffer, Y. Kambarov, S. Köhler, J.M. Olivares, I. Turkoz, C. von Holt, G. Rosso · ASL Napoli 1 Centro, Department of Mental Health, Naples, Italy

2026 ECNP Congress

Introduction

There is a high prevalence of psychiatric comorbidity among people with treatment resistant depression (TRD),[1] underscoringthe importance of effective and sustainable therapy for TRD in the context of other psychiatric diagnoses. Esketamine nasal spray (NS), in combination with an SSRI/SNRI, is indicated for TRD in adults.[2]

Aims

To evaluate effectiveness of esketamine NS, by psychiatric comorbidity status, in adults with TRD attending real-world clinical settings, using data from the Esketamine CoHOrt (ECHO) study. Further details on treatment duration by comorbidity status will be presented in the poster.

Methods

ECHO was a long-term, prospective, non-interventional, open-label study. Participants from Belgium, Germany, Israel, Italy, Netherlands, Spain and Sweden were prescribed esketamine NS per local clinical practice independent of study participation. ECHO comprised a variable duration treatment period (TP), and a 6-month post-treatment follow-up period.

Effectiveness in the TP by psychiatric comorbidity status was assessed by mean change from baseline (CfB) in Montgomery-Åsberg Depression Rating Scale (MADRS) score, summarised with 95% confidence intervals (CIs), remission (MADRS total score ≤10) and response (≥50% improvement in MADRS from treatment initiation) rates. Data are presented from baseline up to 48 weeks in the TP.

Results

570 patients started the TP. Patients received esketamine NS for a mean of ~9 months and median of ~6 months. Patients had severe and chronic TRD at baseline, as presented previously.[3] Outcomes are reported for 568 patients with a comorbidity status recorded at baseline; 45.6% had a current psychiatric comorbidity. Psychiatric comorbidities affecting ≥5% of patients at baseline are shown in the Table.

Mean (SD) MADRS score at baseline was 33.3 (6.8) for the overall cohort, 33.9 (7.0) for those with current psychiatric comorbidities, and 32.7 (6.5) for those without. Mean CfB (95% CI) in MADRS total score at Weeks 4, 24 and 48, respectively, was −10.1 (−11.3, −8.9; N=217)/−10.4 (−11.4, −9.5; N=272), −15.0 (−16.8, −13.1; N=130)/−16.0 (−17.6, −14.5; N=184), and −16.9 (−20.0, −13.9; N=60)/−18.1 (−20.4, −15.7; N=80) in patients with/without current psychiatric comorbidities. All changes were clinically meaningful and statistically significant.

10.1% (22/217)/8.5% (23/272), 22.3% (29/130)/28.3% (52/184) and 26.7% (16/60)/40.0% (32/80) of patients with/without current psychiatric comorbidities achieved remission at Weeks 4, 24 and 48, respectively; 22.1% (48/217)/22.4% (61/272), 45.4% (59/130)/52.7% (97/184), and 50.0% (30/60)/62.5% (50/80) achieved response.

Conclusions

Approximately 50% of patients had a current psychiatric comorbidity at baseline, representing the clinical complexity of patients with TRD in real-world settings. Esketamine NS demonstrated effectiveness regardless of psychiatric comorbidity status. There was rapid improvement and continued reduction in depressive symptoms through 48 weeks of esketamine NS treatment, with clinically meaningful improvements from baseline in mean MADRS scores for patients with and without current psychiatric comorbidity, indicating broad treatment effectiveness.

TABLE. Psychiatric comorbidities affecting ≥5% of patients at baseline

Full analysis set (N=570)
Comorbidity, n (%) Current Lifetime
Generalised anxiety disorder 41 (7.2) 52 (9.1)
Obsessive-compulsive disorder <5% 34 (6.0)
Panic disorder <5% 45 (7.9)
Personality disorder 45 (7.9) <5%
Post-traumatic stress disorder 40 (7.0) 58 (10.2)
Social anxiety disorder <5% 29 (5.1)
Suicide behaviour disorder <5% 43 (7.5)

References

  1. Lundberg J., Cars T., Lööv S., Söderling, J., Sundström, J., Tiihonen, J., Leval, A., Gannedahl, A., Björkholm, C., Själin, M., Hellner, C., 2023. Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study. JAMA Psychiatry 80 (2), 167-175;
  2. 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];
  3. Rosso G., Constant E., De Filippis S., Godinov Y., Häggström L., Ibáñez A., Kambarov Y., Olivier E., Olivares J.M., Reif-Leonhard C., Rive B., Turkoz I., von Holt C., Zeeuws D., Köhler S. EPP015. ECHO: Results from a Non-Interventional Cohort Study of Esketamine Nasal Spray in Treatment Resistant Depression. Presented at the European Congress of Psychiatry, 28–31 March 2026, Prague, Czech Republic.