Intravenous Ketamine for Treatment-Resistant Depression

This will be a randomized, double-blind, placebo-controlled, parallel-group study where adult subjects with treatment refractory major depressive disorder (MDD) will receive 1:1 single IV racemic ketamine (n=15) or normal saline (placebo) (n=15) infusion in an MRI scanner, followed by an optional open-label ketamine infusion. In this innovative comparative study utilizing novel dynamic sliding-window fMRS and liquid chromatography-mass spectrometry (LCMS), we will investigate the dynamic relationship between GABA and Glu levels measured centrally and peripherally, respectively, with change in depression symptoms utilizing the Montgomery Asberg Depression Rating Scale (MADRS).12 Given preclinical models of reduced ACs and glutamatergic function in depression, we will also include an exploratory analysis of ACs metabolomic markers associated with ketamine treatment response.