JAMA Network JAMA Psychiatry : Serial Ketamine Infusions as an Adjunctive Therapy to Inpatient Care for Depression
Oct 22, 2025
Declan M. McLoughlin, an MD and PhD psychiatrist from Trinity College Dublin, shares insights from the KARMA-Dep2 trial on ketamine's role in treating depression. He discusses the differences between esketamine nasal spray and IV ketamine, diving into how sub-anesthetic doses can cause dissociation. The conversation explores the challenges of blinding in trials and the study’s design involving 66 participants. McLoughlin also reveals the mixed outcomes regarding ketamine's antidepressant effects compared to ECT, emphasizing the need for cautious expectations.
AI Snips
Chapters
Transcript
Episode notes
Forms And Delivery Of Ketamine
- Ketamine exists as a racemic mixture; S-ketamine is the nasal-spray form while IV ketamine uses the full mix.
- IV ketamine is given at sub-anesthetic doses over ~40 minutes for antidepressant effects.
Blinding Challenges Due To Dissociation
- Ketamine's dissociative effects make blinding difficult in trials because participants notice pronounced subjective changes.
- Midazolam is a common active control but may still fail to fully mask ketamine's effects.
From Single To Serial Infusions
- Early ketamine studies mostly used single infusions and saline controls, showing rapid but short-lived antidepressant effects.
- McLoughlin's team tested serial infusions to evaluate sustained benefit for inpatients.