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.

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).

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.

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:

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.

None Declared