PCORI Comparative Effectiveness Study-Esketamine (Spravato) vs. Ketamine-Equivalence Study

The purpose of this study is to compare the relative effectiveness, acceptability, and side effects of ketamine delivered through an IV (a drip into the arm) which is not currently FDA approved for use in the treatment of treatment-resistant depression (TRD) and Esketamine (Spravato®), taken as a nasal spray which has received FDA approval for use in the treatment of treatment-resistant depression (TRD) in the treatment of patients with treatment-resistant depression (TRD). The study will look at the following: * How well the treatment helps with symptoms of depression (effectiveness), * How comfortable and willing people are to use the treatment (acceptability), and * How well people can deal with any side effects from the treatment (tolerability). The study will also examine factors that may predict which treatment works better for certain patients.

NCT Number	NCT06713616
Lead Sponsor	Yale University Collaborators: Patient-Centered Outcomes Research Institute
Conditions	Depression
Enrollment	400 participants
Start Date	2025-01-27
Primary Completion	2030-12-31 (estimated)
Study Completion	2030-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-07-31