Outcomes with esketamine nasal spray in patients with or without earlier partial or full response: post hoc analyses of ESCAPE TRD
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.014 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.007 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".