Real-world effectiveness and safety of intranasal esketamine for treatment-resistant depression: Data from the enTRD registry
- 1Department of Psychiatry and Psychotherapy, Division of General Psychiatry, Medical University of Vienna, Vienna, Austria
- 2Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
Abstract
Background: Real-world data for intranasal esketamine in treatment-resistant depression (TRD) are needed to characterize effectiveness, suicidality, and tolerability in routine care. We evaluated induction phase outcomes in outpatients with TRD treated at the University Hospital Vienna.
Methods: This retrospective single-center registry study included adults with TRD initiating supervised intranasal esketamine. The primary endpoint was the change in clinician-rated depressive symptom severity (MADRS) from the pre-treatment (PV) to the end of induction (EOI) visit. MADRS scores across baseline (BL), PV, and EOI were analyzed using a mixed model for repeated measures. Secondary outcomes included MADRS three-factor change, self-rated depression score trajectories (PHQ-9), response/remission rates, suicidal ideation, and tolerability.
Results: Of 229 screened patients, 176 initiated esketamine and 156 completed induction. MADRS at BL was 31.5 (SD 6.4), PHQ-9 was 18.5 (SD 4.7). In the primary model, adjusted mean MADRS was 30.3 at PV and 17.7 at EOI, yielding a change of −12.5 points (95%CI −14.1 to −11.0; p < 0.001; Hedges’ g = 1.8). All MADRS factors improved, with the largest reduction in the affective–anhedonic domain. PHQ-9 decreased steadily across treatments. Remission was 27.2% and response 57.4% at EOI. Suicidal ideation decreased significantly; no suicide or serious self-harm occurred during induction. Adverse events (AEs) were recorded in 34.7%, with AE-related discontinuation in 3.4%.
Conclusions: Esketamine induction was associated with marked improvement in depressive symptoms and suicidality, with acceptable tolerability under supervised administration. Longer-term registry follow-up and controlled comparative studies are needed to further define the benefit–risk profile beyond induction phase.
Related
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- Baseline Response Criterion and Changes in Emotional Bias as Markers of Esketamine Response in Treatment-Resistant Depression
- Oral Esketamine Maintenance Treatment for Treatment‐Resistant Depression: Clinical Outcomes During an Off‐Label Treatment Program
BibTeX
@article{preiss2026realworld,
title = {{Real-world effectiveness and safety of intranasal esketamine for treatment-resistant depression: Data from the enTRD registry}},
author = {Maximilian Preiss and Valentin Popper and Luna Helene Charlotte Faber and Theresa Baumgartner and Philip Miguel Baberis-Martinez and Edda Winkler-Pjrek and Gregor Gryglewski and Lucie Bartova and Siegfried Kasper and Dan Rujescu-Balcu and Lukas Pezawas},
journal = {European Psychiatry},
year = {2026},
month = jun,
doi = {10.1192/j.eurpsy.2026.12234},
url = {https://doi.org/10.1192/j.eurpsy.2026.12234},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Real-world effectiveness and safety of intranasal esketamine for treatment-resistant depression: Data from the enTRD registry
AU - Maximilian Preiss
AU - Valentin Popper
AU - Luna Helene Charlotte Faber
AU - Theresa Baumgartner
AU - Philip Miguel Baberis-Martinez
AU - Edda Winkler-Pjrek
AU - Gregor Gryglewski
AU - Lucie Bartova
AU - Siegfried Kasper
AU - Dan Rujescu-Balcu
AU - Lukas Pezawas
PY - 2026
DA - 2026/06/23
JO - European Psychiatry
DO - 10.1192/j.eurpsy.2026.12234
UR - https://doi.org/10.1192/j.eurpsy.2026.12234
AB - Background: Real-world data for intranasal esketamine in treatment-resistant depression (TRD) are needed to characterize effectiveness, suicidality, and tolerability in routine care. We evaluated induction phase outcomes in outpatients with TRD treated at the University Hospital Vienna. Methods: This retrospective single-center registry study included adults with TRD initiating supervised intranasal esketamine. The primary endpoint was the change in clinician-rated depressive symptom severity (MADRS) from the pre-treatment (PV) to the end of induction (EOI) visit. MADRS scores across baseline (BL), PV, and EOI were analyzed using a mixed model for repeated measures. Secondary outcomes included MADRS three-factor change, self-rated depression score trajectories (PHQ-9), response/remission rates, suicidal ideation, and tolerability. Results: Of 229 screened patients, 176 initiated esketamine and 156 completed induction. MADRS at BL was 31.5 (SD 6.4), PHQ-9 was 18.5 (SD 4.7). In the primary model, adjusted mean MADRS was 30.3 at PV and 17.7 at EOI, yielding a change of −12.5 points (95%CI −14.1 to −11.0; p < 0.001; Hedges’ g = 1.8). All MADRS factors improved, with the largest reduction in the affective–anhedonic domain. PHQ-9 decreased steadily across treatments. Remission was 27.2% and response 57.4% at EOI. Suicidal ideation decreased significantly; no suicide or serious self-harm occurred during induction. Adverse events (AEs) were recorded in 34.7%, with AE-related discontinuation in 3.4%. Conclusions: Esketamine induction was associated with marked improvement in depressive symptoms and suicidality, with acceptable tolerability under supervised administration. Longer-term registry follow-up and controlled comparative studies are needed to further define the benefit–risk profile beyond induction phase.
SN - 0924-9338
SN - 1778-3585
ER -