2018 · RCT
Daly et al. 2018 - esketamine pivotal trial
Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in TRD
Medically reviewed by: Pending medical review(draft)Last updated: June 4, 2026Evidence: Daly EJ et al.. JAMA Psychiatry, 2018.
Population
67 patients with TRD
Intervention
Intranasal esketamine + oral antidepressant
Comparator
Placebo nasal spray + oral antidepressant
Primary outcome
Change in MADRS at day 8
Key findings
- Significant separation from placebo
- Dose-response relationship
- Supported the FDA approval pathway for Spravato
Limitations
- Industry-sponsored
- Modest effect size
- Functional unblinding concerns
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