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Blinded Trial Finds No Added Benefit From Repeated Ketamine Infusions for Hospitalized Depression

The JAMA Psychiatry KARMA-Dep 2 study reports that widespread unblinding undermines prior efficacy claims.

Overview

  • Inpatients were randomized to receive up to eight adjunctive infusions over four weeks of either ketamine or the psychoactive comparator midazolam alongside standard care.
  • No difference emerged on the primary clinician-rated Montgomery-Åsberg Depression Rating Scale at the end of treatment.
  • Patient-reported symptoms on the QIDS-SR-16 also did not differ between groups, and there were no advantages on cognitive, economic, or quality-of-life outcomes.
  • Outcomes remained null through a six-month follow-up, with the lead investigator stating that adjunctive ketamine offered no added benefit under rigorous trial conditions.
  • Trial leaders emphasized that most patients and raters correctly guessed treatment allocation, highlighting the need to assess blinding success and to conduct further rigorous randomized comparisons.