Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression
Randomized, double-blind, placebo-controlled crossover Phase II trial (n=50) testing IV (2R,6R)-HNK infusions (0.25→2.0 mg/kg, up to four infusions over 2 weeks) versus saline placebo in treatment-resistant MDD.
Details
This single-site, randomized, double-blind, placebo-controlled crossover study evaluates the antidepressant efficacy and safety of (2R,6R)-hydroxynorketamine (HNK) in adults with treatment-resistant major depressive disorder.
Participants receive four IV infusions over two weeks of HNK (starting 0.25 mg/kg with a target of 2.0 mg/kg, with escalation rules) in one treatment period and four matched saline placebo infusions in the other; periods are crossed over.
Primary outcome is change in MADRS total score at day 12; secondary outcomes include remission and response rates, suicidality measures (C-SSRS, SSI, MADRS item 10), mood/anxiety scales, cognitive tasks and neuroimaging/MRS markers of glutamate and MEG/fMRI measures.