28th National Clinical Education Symposium Presentation Abstracts

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21 APRIL 2026, TUESDAY
PP-29 Long-Term Outcomes of Intranasal Esketamine in Treatment-Resistant Depression: Evidence from Clinical Trials and Real-World Studies

PP-29 Long-Term Outcomes of Intranasal Esketamine in Treatment-Resistant Depression: Evidence from Clinical Trials and Real-World Studies

Çağla İyice1, Deniz Kaya1, Güneş Devrim Kıcalı1

1. Department of Psychiatry, Sıtkı Koçman University, Muğla,Türkiye

DOI: 10.5080/61upk.ozt518 Page 226

BACKGROUND AND AIM:Treatment-Resistant Depression (TRD) is defined as failure to respond to at least two adequate antidepressant trials in the current episode. Esketamine, a non-competitive NMDA receptor antagonist, promotes synaptogenesis through mTORC1 activation and BDNF release. This study aims to evaluate esketamine’s relapse prevention capacity, long-term safety (up to 6.5 years), and comparative efficacy by synthesizing data from clinical trials (SUSTAIN, ESCAPE-TRD) and real-world evidence (REAL-ESK).
METHODS (Ethics Committee Approval must be obtained and the number should be specified.):A comprehensive literature review was conducted using PubMed, Cochrane Library, and Google Scholar (2019–2025). Phase studies (SUSTAIN-1, SUSTAIN-2, SUSTAIN-3), comparative trials (ESCAPE-TRD), and observational real-world data (REAL ESK) were included. Ethics committee approval is not required for systematic reviews.
RESULTS:In SUSTAIN-1 (N=297), esketamine reduced relapse risk by 70% (p<0.001) in stable responders and 51% (p=0.003) in stable remitters. SUSTAIN-2 reported a 58.2% remission rate at one year. In ESCAPE-TRD (N=676), esketamine demonstrated superiority over quetiapine, achieving 27.1% remission at week 8 (p=0.003) and 21.7% relapse-free remission through week 32. SUSTAIN-3 (N=1148) showed that remission rates approached 50% and were maintained for up to 6.5 years under intermittent dosing. REAL-ESK, a multicenter realworld cohort, reported a 40.6% remission rate; in the subsequent trajectory study (n?78), 55.1% of patients maintained clinical benefit during continuation treatment. Across studies, 40–50% non-response rates reflect the persistent clinical burden of TRD.
CONCLUSIONS:Esketamine represents an important long-term treatment option for TRD, supported by sustained efficacy and safety data from clinical trials and extension studies. Nevertheless, reported success rates should be interpreted considering enriched trial designs, open-label extensions, and potential sponsor relationships. This poster synthesizes long-term clinical and real-world data to provide a balanced overview of esketamine’s role in sustained TRD management .Keywords: Treatment-Resistant Depression, Intranasal Esketamine, Long-Term Outcomes, Real-World Evidence