Outcomes with esketamine nasal spray in patients with or without earlier partial or full response: post hoc analyses of ESCAPE TRD

Introduction There are limited data to guide treatment continuation decisions for clinicians caring for patients with treatment resistant depression (TRD). Identifying the magnitude of early improvement (at Weeks 4 and 8) as a predictor of long-term outcomes for TRD can guide treatment continuation decisions. Objectives To evaluate the probability of achieving response or remission by Week 32 in patients with TRD after 4 or 8 weeks of esketamine nasal spray (ESK-NS) treatment, flexibly dosed in combination with an ongoing selective serotonin/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI). Methods ESCAPE‑TRD was a randomised phase IIIb trial comparing the efficacy of ESK-NS versus quetiapine extended release, both in combination with an ongoing SSRI/SNRI, in patients with TRD (Reif et al. NEJM 2023; 389 1298–309). Remission was defined as a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10, and partial response and response as ≥25% and ≥50% improvements, respectively, in total MADRS score (or remission). Long-term outcomes were based on the best outcome on-treatment across 32 weeks (≥1 instance of response or remission) from earliest outcome endpoint onwards. Non-responder imputation (NRI) was applied after treatment discontinuations. Results 336 patients were randomised to ESK-NS; 334 received ≥1 dose. Table 1 shows long-term outcomes following at least partial response, response or no partial response at Weeks 4 and 8. For example, among those who had at least a partial response at Week 4, 94.1% and 79.8% had response and remission by Week 32, respectively. Image 1: Conclusions This analysis demonstrated a relationship between short- and long-term outcomes. Presence of at least partial response at Week 4 led to more favourable outcomes by Week 32. Moreover, most patients with response by Week 4 achieved remission by Week 32. Continued symptom improvements were observed beyond the induction phase even in some patients with no partial response at Week 4. Disclosure of Interest None Declared