Key Takeaways
Extended Takeaways
- The antidepressant signal emerged within 4 hours after the first dose and remained generally present through day 25, suggesting esketamine can provide symptom relief during the interval before a newly initiated or optimized oral antidepressant is expected to take effect.
- Remission was more common with esketamine, with a treatment difference (95% CI) of 9.8% (0.87 to 18.77) at 24 hours post-first dose and 16.1% (3.20 to 28.94) on day 25, 4 hours postdose.
- Lack of a statistically significant advantage on suicidality ratings at 24 hours should be interpreted in the context of strong background intervention: all patients received psychiatric hospitalization, intensive clinical contact, and newly initiated or optimized antidepressant treatment, and approximately three-fourths also received ≥ 1 concomitant benzodiazepine during the double-blind phase.
- Patients with greater baseline severity appeared to derive larger benefit: the mean between-group difference [95% CI] in MADRS total score at 24 hours was −6.53 [−10.88 to −2.18] in those with MADRS total score > median and −5.53 [−9.11 to −1.95] in those with a prior suicide attempt.
- Tolerability planning is important in acute care settings because 21 patients (18.6%) in the esketamine + standard-of-care group had a dose reduction to 56 mg due to intolerance, primarily on second dosing, and 13/113 (11.5%) had an MOAA/S score ≤ 3 at any time during the double-blind phase.
- Most adverse events with esketamine were transient and clustered around administration: 91.0% occurred on intranasal dosing days, and 94.9% of those resolved on the same day, which can help inform monitoring and discharge workflows.
