Intravenous Ketamine for Treatment-Resistant Depression (G2K)

This randomised, double-blind, placebo-controlled, parallel-group trial (n=30) will investigate the effects of intravenous ketamine (35/70kg) compared to normal saline (placebo) on central and peripheral levels of GABA and glutamate, and the associated changes in depression symptoms.

Conducted by the Mayo Clinic, this study focuses on adults aged 18-65 with treatment-resistant depression (TRD). The trial will explore the dynamic relationship between neurotransmitter changes (GABA and glutamate) during a 40-minute IV infusion of ketamine or saline, and its impact on depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Using advanced functional MRI (fMRS) and liquid chromatography-mass spectrometry (LCMS), the researchers aim to identify biomarkers that correlate with ketamine’s therapeutic effects.

The primary aim is to assess the correlation between changes in GABA and glutamate levels and depression severity over a 24-hour period following infusion. Secondary outcomes will include measures of rapid response, anhedonia, and neurocognitive function, along with other scales assessing the severity of depression and suicidality. The study aims to enhance the understanding of ketamine’s neurobiological effects and its potential role in treating TRD.

Trial Details

The purpose of this study is to to evaluate the relationships between peak (% change from baseline) central GABA and Glu levels during a 40-min IV ketamine or normal saline infusion utilizing fMRS, and change in peripheral GABA and Glu levels from baseline to 24-hr postinfusion utilizing LCMS, with baseline to 24-hr post-infusion change in depression (MADRS) in 30 TRD adults. 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.

Trial Number NCT06668571

Data attribution

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