A randomised controlled trial of oral S-ketamine as add-on medication for patients with treatment-resistant major depressive disorder

Randomised, double‑blind, parallel‑group add‑on trial comparing oral S‑ketamine versus matched placebo in 128 inpatients and outpatients with treatment‑resistant major depressive disorder (HDRS17 >18), continuing their existing antidepressant medication.

Treatment is administered three times daily for 6 weeks with tapered start and finish. Primary outcome is change in HDRS17 score and response rates; secondary assessments include multiple clinical scales, neuroimaging, pharmacokinetics, biomarkers and health‑economic outcomes.