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7T 1H-MRS in major depressive disorder: a Ketamine Treatment Study.

Jennifer W. Evans, Níall Lally, Li An, Ningzhi Li, Allison C. Nugent, Dipavo Banerjee, Sam L Snider, Jun Shen, Jonathan P. Roiser, Carlos A. Zarate

Neuropsychopharmacology August 2018 DOI: 10.1038/s41386-018-0057-1 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled, crossover study Peer reviewed
Sample size 37
Population 20 medication-free subjects with major depressive disorder and 17 healthy volunteers
Intervention Ketamine
Duration Scans at baseline and 24 hours post ketamine and post-placebo infusions
Measures Proton magnetic resonance spectroscopy (1H-MRS) at 7T
Topics Depression Esketamine Ketamine
Key points No significant between-group differences in 1H-MRS-measured metabolites were observed at baseline, and baseline glutamate levels did not predict antidepressant response. The authors suggest that any infusion-induced glutamate increases at 24 hours post ketamine were below the sensitivity of the technique, may occur in brain regions other than the pregenual anterior cingulate, or may be confined to subgroups of MDD subjects with a differential glutamate response.

Abstract

The glutamatergic modulator ketamine has striking and rapid antidepressant effects in major depressive disorder (MDD), but its mechanism of action remains unknown. Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive method able to directly measure glutamate levels in vivo; in particular, glutamate and glutamine metabolite concentrations are separable by 1H-MRS at 7T. This double-blind, placebo-controlled, crossover study that included 1H-MRS scans at baseline and at 24 h post ketamine and post-placebo infusions sought to determine glutamate levels in the pregenual anterior cingulate (pgACC) of 20 medication-free MDD subjects and 17 healthy volunteers (HVs) 24 h post ketamine administration, and to evaluate any other measured metabolite changes, correlates, or predictors of antidepressant response. Metabolite levels were compared at three scan times (baseline, post-ketamine, and post-placebo) in HVs and MDD subjects at 7T using a 1H-MRS sequence specifically optimized for glutamate. No significant between-group differences in 1H-MRS-measured metabolites were observed at baseline. Antidepressant response was not predicted by baseline glutamate levels. Our results suggest that any infusion-induced increases in glutamate at the 24-h post ketamine time point were below the sensitivity of the current technique; that these increases may occur in different brain regions than the pgACC; or that subgroups of MDD subjects may exist that have a differential glutamate response to ketamine.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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