Racemic Ketamine vs S(+)-Esketamine for TRD: Bicentric Double-Blind RCT (UFBA Brazil, UMIN000032355)

Bicentric double-blind active-controlled RCT registered on Japan UMIN registry (UMIN000032355; Psychiatry Research 2021; Araújo-de-Freitas L, Lacerda ALT, Quarantini LC et al.; Universidade Federal da Bahia — UFBA, Salvador, Brazil; PMID 34153630). Participants: adults (≥18 yr) with DSM TRD meeting criteria for MDD and failure of ≥1 adequate antidepressant ≥12 weeks; exclusions: current ECT, psychosis, intellectual disability, unstable cardiac disease, illicit drug use, ketamine abuse history. 1:1 randomisation to: IV ketamine (racemic) 0.5 mg/kg over 40 min OR IV S(+)-esketamine 0.25 mg/kg over 40 min (equianalgesic dose, based on ~2× potency of S-enantiomer). Single infusion. Ongoing antidepressants maintained (no change within 15 days before randomisation or during follow-up). Neuropsychological battery assessed at baseline, 24h, and day 7: WASI, WAIS-III Digit Span, Corsi Block-Tapping, Five Digit Test (FDT), Rey AVLT. CONSORT-compliant; UMIN registration confirmed in methods. CT.gov: 0 hits.