Long-term treatment with esketamine nasal spray in patients with treatment resistant depression: Results from the ESCAPE-LTE study.
Andreas Reif, Yağcıoğlu Ae Anıl, Istvan Bitter, J Buyze, Richard Frey, Fu Dj, Yordan Godinov, Lars Haggström, Yerkebulan Kambarov, René E Nielsen, Albino J Oliveira-Maia, Christian von Holt, Young Ah, Wiesław Jerzy Cubała
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology June 1, 2026 DOI: 10.1016/j.euroneuro.2026.112801 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-arm, long-term extension of a rater-blinded, randomized, active-controlled trial Peer reviewed |
|---|---|
| Sample size | 183 |
| Population | Adults with treatment-resistant depression |
| Intervention | Esketamine nasal spray |
| Duration | 136 weeks of treatment, 138 weeks including safety follow-up |
| Topics | Depression Esketamine |
| Keywords | Efficacy Long-term Safety Tolerability Treatment resistant depression |
| Citations | 3 |
| Registration | NCT04829318 NCT04338321 |
| Key findings | The vast majority of patients with treatment-resistant depression who achieved remission with esketamine nasal spray did not relapse over 136 weeks of treatment, and no new safety concerns were identified. |
Abstract
Optimising patient outcomes in treatment resistant depression (TRD) requires treatments which provide sustained remission, without relapse, and tolerability in the long term. ESCAPE-LTE (NCT04829318) was a phase IV, single-arm, 2-year (104 weeks) long-term extension of ESCAPE-TRD (NCT04338321; 32 weeks), a rater-blinded, randomised, active-controlled trial, which evaluated the safety, tolerability and efficacy of esketamine nasal spray (NS), alongside an ongoing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor, in patients with TRD. The primary endpoints were the proportion of patients who reported treatment-emergent adverse events (TEAEs) or suicidal ideation and behaviour (using the Columbia-Suicide Severity Rating Scale). Effectiveness was assessed using the Montgomery-Åsberg Depression Rating Scale, Clinical Global Impression-Severity scale, Patient Health Questionnaire-9 and EuroQol 5-Dimension 5-Level questionnaire. Outcomes are reported from ESCAPE-TRD baseline to the end of ESCAPE-LTE (136 weeks of treatment, 138 weeks including safety follow-up). In patients who entered ESCAPE-LTE (N = 183), TEAEs and serious TEAEs were observed in 96.7% and 8.2%, respectively. 98.3% of TEAEs occurring on dosing days resolved same-day; few patients discontinued due to TEAEs during ESCAPE-LTE (3.3%). 151/160 (94.4%) patients who were non-suicidal at baseline remained non-suicidal to the end of ESCAPE-LTE. In the subgroup with remission in ESCAPE-TRD, 79.2% did not relapse or discontinue treatment throughout ESCAPE-LTE; the overall relapse rate for patients achieving remission across both studies was 6.9%. The vast majority of patients with TRD who achieved remission with esketamine NS did not relapse over 136 weeks of treatment; no new safety concerns were identified, and the safety profile was consistent with short-term studies.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.