Study M087
Study name | Rotroff DM 2016 |
Title | Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants |
Overall design | In this study, a pharmacometabolomics approach was used to map global metabolic effects of these compounds in treatment-refractory major depressive disorder (MDD) patients upon 2 h from infusion with ketamine or its S-enantiomer, esketamine. In the ketamine trial, patients were divided into ketamine group (intravenous ketamine 0.5 mg/kg, n = 33) and placebo group (n = 12). In the esketamine trial, patients were divided into esketamine group (IV infusion of esketamine 0.20 or 0.40 mg/kg, n = 20) and placebo group (n = 10). The plasma sample used for the metabolomics assay was obtained 2 h from the first ketamine or placebo infusion. Two complementary metabolomics platforms were used to provide broad biochemical coverage. In addition, we investigated whether changes in particular metabolites correlated with treatment outcome. Each metabolite was tested to determine whether the change from pre- to post exposure was significantly different. Each pre-treatment metabolite level and change in metabolite level was also tested for association with change in MADRS score. |
Study Type | Type2; Type4; |
Data available | https://www.nature.com/articles/tp2016145#supplementary-information |
Organism | Human; |
Categories of depression | Depressive disorder; Treatment-resistant depression; Treatment-resistant depression; |
Criteria for depression | DSM-IV-TR diagnosed MDD, 30-item Inventory of Depressive Symptomatology-Clinician rated >= 34 |
Sample size | 75 |
Tissue | Peripheral; Blood; Plasma; |
Platform | MS-based; GC-MS: Agilent 6890 gas chromatograph (Santa Clara, CA) with Leco Pegasus IV time of flight mass (TOF) spectrometer; MS-based; LC-MS: Biocrates AbsoluteIDQ® p180 kit assay (patent US 2007/0004044); |
PMID | |
DOI | |
Citation | Rotroff DM, Corum DG, Motsinger-Reif A, et al. Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants. Transl Psychiatry 2016;6(9):e894. |
Metabolite | Glyceric acid; Citric acid; Pyroglutamic acid; 3-Hydroxybutyric acid; L-Tryptophan; L-Glutamic acid; L-Threonine; Arachidonic acid; L-Methionine; L-Lactic acid; L-Alanine; L-Tyrosine; D-Fructose; D-Glucose; L-Arginine; Threonic acid; Propionylcarnitine; Butyrylcarnitine; Indoleacetic acid; Gamma-Tocopherol; Ethanolamine; Indolelactic acid; D-Xylitol; Gluconic acid; Cholesterol; Ornithine; L-Acetylcarnitine; Alpha-Tocopherol; D-Galactose; D-Mannose; Isovalerylcarnitine; D-Threitol; D-Tagatose; Isothreonic acid; Galactonic acid; Dehydroabietic acid; Methionine sulfoxide; |
