2026 ECNP Congress

PS01-1121

Trauma burden and personality as moderators of esketamine response in treatment-resistant depression: interim analysis of a naturalistic registry

Maria Teresa Gonzalez Salvador — E. Díaz-Pinto, A. García-Alija, P. Iniesta-Casas, B. Alonso-Galán, N.E. Perales-Valdés, J. Mijallo Rodríguez, L. Egüen Recuero, B. Sanz-Aranguez Avila · Puerta de Hierro University Hospital, Department of Psychiatry, Madrid, Spain

2026 ECNP Congress

Background

Treatment-resistant depression (TRD) represents a major public health burden, with approximately 30% of patients failing to respond to two or more adequate antidepressant trials. Intranasal esketamine (ESK-NS) — a glutamate NMDA receptor antagonist acting as an open-channel blocker per Neuroscience-based Nomenclature (NbN) [1] — has received regulatory approval for TRD based on the TRANSFORM-2 and SUSTAIN-1 pivotal trials [2,3]. Real-world data are still accumulating [5], and the role of trauma burden and personality pathology as moderators of antidepressant response has not been systematically investigated.

Methods

An ongoing prospective naturalistic registry of adult TRD patients initiating ESK-NS at a tertiary psychiatric unit in Madrid, Spain. An interim analysis is reported (N=20 enrolled; N=13 completed protocol at time of analysis; registry ongoing). The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline, end of induction (weeks 4–5), and end of treatment. The Clinical Global Impression severity (CGI-S) and change (CGI-C) scales, the Impact of Event Scale-Revised (IES-R), and the Personality Inventory for DSM-5 (PID-5; five domains) were collected at baseline; treatment satisfaction was assessed with the validated Treatment Satisfaction Questionnaire for Medication (TSQM) [4] at discharge. Spearman rank correlations were computed between baseline IES-R and PID-5 domain scores and MADRS change from baseline to end of treatment in patients with complete paired data.

Results

Mean baseline MADRS was 38.8 (SD 7.7; n=16). In the subgroup with complete numerical MADRS at all three time-points (n=8), scores decreased from 38.5 (SD 10.1) at baseline to 30.4 (SD 9.1) at end of induction and 20.6 (SD 13.4) at end of treatment; a ≥50% MADRS reduction was achieved in 4/8 patients (50%). Categorical improvement of ≥1 severity step was observed in 9/12 (75%) assessable patients. CGI-C indicated any improvement in 8/10 (80%) completers, with 4/10 (40%) rated “much improved” or better. Treatment satisfaction (TSQM) was ≥“somewhat satisfied” in 8/11 (73%) patients at discharge.

Clinically significant trauma burden (IES-R ≥33) was present in 11/12 (92%) assessable patients (mean 59.8, SD 24.4). The most prevalent PID-5 personality domains were Negative Affect and Detachment. Correlation analysis revealed a statistically significant negative association between baseline IES-R score and antidepressant response at end of treatment (Spearman r = −0.714, p = 0.047, n=8): greater baseline trauma burden was associated with lesser MADRS improvement. Exploratory analysis of PID-5 domains revealed a non-significant positive trend between Antagonism and treatment response (Spearman r = 0.655, p = 0.078), warranting cautious interpretation and replication in larger samples.

Conclusions

In this real-world interim analysis, ESK-NS produced clinically meaningful antidepressant effects alongside high treatment satisfaction. The significant correlation between baseline trauma burden and antidepressant response supports the routine assessment of post-traumatic stress pathology prior to initiating glutamate NMDA receptor-targeted pharmacotherapy in TRD. These preliminary data suggest that comorbid trauma exposure may moderate response to ESK-NS, an observation that requires replication in adequately powered prospective studies.

KEYWORDS:

treatment-resistant depression; esketamine; intranasal; NMDA receptor antagonist; trauma; personality; naturalistic study

References

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