Open-label, interventional mechanistic trial (n=120) using intravenous ketamine (0.5 mg/kg over 40 minutes, max 60 mg; three alternate-day infusions in MDD participants) to study molecular and connectome correlates of rapid antidepressant and anti-suicidal effects.
This mechanistic clinical trial will evaluate molecular and imaging correlates of rapid antidepressant action of subanesthetic intravenous ketamine in patients with major depressive disorder.
Ninety depressed, medication-free participants will receive three alternate-day ketamine infusions (0.5 mg/kg over 40 minutes, maximum 60 mg) and be scanned at baseline and two post-treatment time points; thirty healthy controls will be scanned at two time points without treatment.
Outcomes include 7T structural, resting-state fMRI and DWI connectome measures, and molecular/gene expression profiles from olfactory-epithelium-derived neurons; mediation analyses will link molecular changes to connectome alterations and clinical improvement.
Intravenous ketamine 0.5 mg/kg over 40 minutes (max 60 mg); depressed participants receive three alternate-day infusions; healthy controls scanned without treatment.
0.5 mg/kg over 40 minutes; maximum 60 mg; 3 alternate-day treatments for MDD group