Outcomes
SECONDARY, REMISSION, SIDE EFFECT
The primary outcome was remission, defined as a MADRS score ≤10, assessed 3–4 days after the final treatment at the end of the 4-week RCT. Interrater reliability of MADRS raters was established by viewing and rating pre-recorded standardised interviews, with an intra-class correlation coefficient of >0.8 required against expert ratings. Structured assessments evaluated safety at each treatment session (acute effects), emerging or cumulative effects between sessions and changes from baseline to the RCT end and 4-week follow-up (long-term effects) using a prototype of the Ketamine Side Effect Tool (KSET)Key secondary outcomes over the RCT period were: remission based on a MADRS score ≤12 (for comparison with pivotal intranasal esketamine studies);See Supplementary material and trial protocol for further details.