Randomized, double-blinded, midazolam-controlled crossover trial (n=40) testing single IV ketamine (0.5 mg/kg over 40 minutes) versus midazolam (30 µg/kg) in treatment-resistant depression to identify predictors of rapid and sustained response.
This randomized, double-blind, midazolam-controlled crossover study will recruit 40 participants with treatment-resistant depression to identify clinical, behavioural, and neurophysiological predictors of response to a single infusion of IV ketamine (0.5 mg/kg over 40 minutes).
Participants receive two infusions 21 days apart (ketamine and midazolam in counterbalanced order). Outcomes include MADRS at 24 hours, 7 and 14 days, weekly self-report (QIDS-SR16), measures of anhedonia (SHAPS, DARS, PVSS-21), actigraphy, EEG, speech sampling, and computerized tasks to build predictive models of rapid and sustained antidepressant response.
The trial uses midazolam as an active psychoactive comparator to improve blinding; safety measures and medication restrictions (e.g., grapefruit juice, benzodiazepines) are in place to reduce interaction risks.
IV ketamine 0.5 mg/kg over 40 minutes; crossover with midazolam comparator.
Infusion 0.5 mg/kg over 40 minutes; one infusion per treatment period.
IV midazolam 30 µg/kg over 40 minutes as active comparator to preserve blinding.
Midazolam 30 µg/kg over 40 minutes (encoded as active comparator in notes).