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2018 · RCT

Daly et al. 2018 - esketamine pivotal trial

Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in TRD

Written by: Ira ZootMedical review status: Not yet clinically reviewed.Last updated: June 4, 2026Evidence: Daly EJ et al.. JAMA Psychiatry, 2018.

This page has been written and edited by the publisher. It has not been reviewed by a licensed clinician.

Quick answer
Why this study matters
One of the trials supporting FDA approval of esketamine (Spravato) in 2019, the first new mechanistic class of antidepressant in decades.
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

Read the original study →

Disclaimer
Educational summary only. A single study - even a landmark one - does not establish clinical practice. Discuss treatment decisions with a qualified clinician.
About the author
Ira Zoot

Publisher and editor of Ketalux, based in Chicago, Illinois. Ira is a ketamine therapy patient, not a clinician. This is editorial review, not medical review: Ira is not a licensed clinician and does not provide diagnosis or medical care. Ketalux does not accept compensation from providers in exchange for favorable editorial coverage, evidence ratings, recommendations, patient referrals, or organic provider ranking. Read the full publisher disclosure →

Educational use only. The content on this page is provided for general educational purposes and does not constitute medical advice, diagnosis, or treatment. Ketamine and related therapies carry risks and are appropriate only under qualified medical supervision. Always consult a licensed healthcare professional about your individual situation. Information may change as research evolves.