Intravenous Ketamine for Treatment-Resistant Depression

Summary

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.

Timeline

Start

2025-02-10

Primary completion

2027-12-31

Completion

2027-12-31

Publications

• Background Singh B, Vande Voort JL, Pazdernik VK, Frye MA, Kung S. Treatment-resistant depression patients with baseline suicidal ideation required more treatments to achieve therapeutic response with ketamine/esketamine. J Affect Disord. 2024 Apr 15;351:534-540. doi: 10.1016/j.jad.2024.01.262. Epub 2024 Jan 30.
• Background Singh B, Bobo WV, Rasmussen KG, Stoppel CJ, Rico JA Jr, Schak KM, Biernacka JM, Frye MA, Vande Voort JL. The Association Between Body Mass Index and Remission Rates in Patients With Treatment-Resistant Depression Who Received Intravenous Ketamine. J Clin Psychiatry. 2019 Nov 12;80(6):19l12852. doi: 10.4088/JCP.19l12852. No abstract available.
• Background Frye MA, Blier P, Tye SJ. Concomitant benzodiazepine use attenuates ketamine response: implications for large scale study design and clinical development. J Clin Psychopharmacol. 2015 Jun;35(3):334-6. doi: 10.1097/JCP.0000000000000316. No abstract available.
• Background Singh B, Parikh SV, Voort JLV, Pazdernik VK, Achtyes ED, Goes FS, Yocum AK, Nykamp L, Becerra A, Smart L, Greden JF, Bobo WV, Frye MA, Burdick KE, Ryan KA. Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial. Psychiatry Res. 2024 May;335:115829. doi: 10.1016/j.psychres.2024.115829. Epub 2024 Feb 28.
• Background Parikh SV, Vande Voort JL, Yocum AK, Achtyes E, Goes FS, Nykamp L, Singh B, Lopez-Vives D, Sera CE, Maixner D, Tarnal V, Severe J, Bartek S, Tye SJ, Rico J, Stoppel CJ, Becerra A, Smart L, Miller CR, Frye MA, Greden JF, Bobo WV. Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression. J Affect Disord. 2024 Mar 1;348:143-151. doi: 10.1016/j.jad.2023.12.033. Epub 2023 Dec 22.
• Background Singh B, Kung S, Pazdernik V, Schak KM, Geske J, Schulte PJ, Frye MA, Vande Voort JL. Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study. J Clin Psychiatry. 2023 Feb 1;84(2):22m14548. doi: 10.4088/JCP.22m14548.
• Background Vande Voort JL, Morgan RJ, Kung S, Rasmussen KG, Rico J, Palmer BA, Schak KM, Tye SJ, Ritter MJ, Frye MA, Bobo WV. Continuation phase intravenous ketamine in adults with treatment-resistant depression. J Affect Disord. 2016 Dec;206:300-304. doi: 10.1016/j.jad.2016.09.008. Epub 2016 Sep 12.
• Background Brix MK, Ersland L, Hugdahl K, Dwyer GE, Gruner R, Noeske R, Beyer MK, Craven AR. Within- and between-session reproducibility of GABA measurements with MR spectroscopy. J Magn Reson Imaging. 2017 Aug;46(2):421-430. doi: 10.1002/jmri.25588. Epub 2017 Feb 15.
• Background Dubin MJ, Mao X, Banerjee S, Goodman Z, Lapidus KA, Kang G, Liston C, Shungu DC. Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. J Psychiatry Neurosci. 2016 Apr;41(3):E37-45. doi: 10.1503/jpn.150223.
• Background Port JD, Singh B, Frye MA. Dynamic Sliding-Window MRS Method for Measuring Changes in Glutamate and GABA in Patients with Major Depressive Disorder. presented at: ISMRM & SMRT Virtual Conference & Exhibition; 2020; Virtual https://www.ismrm.org/20/program_files/DP01-09.htm#044
• Background Singh B, Vande Voort JL, Riva-Posse P, Pazdernik VM, Frye MA, Tye SJ. Ketamine-Associated Change in Anhedonia and mTOR Expression in Treatment-Resistant Depression. Biol Psychiatry. 2023 Jun 15;93(12):e65-e68. doi: 10.1016/j.biopsych.2022.10.007. Epub 2023 Jan 25. No abstract available.
• Background Rotroff DM, Corum DG, Motsinger-Reif A, Fiehn O, Bottrel N, Drevets WC, Singh J, Salvadore G, Kaddurah-Daouk R. 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 Sep 20;6(9):e894. doi: 10.1038/tp.2016.145.
• Background Singh B, Port JD, Voort JLV, Coombes BJ, Geske JR, Lanza IR, Morgan RJ, Frye MA. A preliminary study of the association of increased anterior cingulate gamma-aminobutyric acid with remission of depression after ketamine administration. Psychiatry Res. 2021 Jul;301:113953. doi: 10.1016/j.psychres.2021.113953. Epub 2021 Apr 20.
• Background Singh B, Port JD, Pazdernik V, Coombes BJ, Vande Voort JL, Frye MA. Racemic ketamine treatment attenuates anterior cingulate cortex GABA deficits among remitters in treatment-resistant depression: A pilot study. Psychiatry Res Neuroimaging. 2022 Mar;320:111432. doi: 10.1016/j.pscychresns.2021.111432. Epub 2021 Dec 24. No abstract available.
• Background Singh B, MahmoudianDehkordi S, Voort JLV, Han X, Port JD, Frye MA, Kaddurah-Daouk R; Mood Disorders Precision Medicine Consortium (MDPMC). Metabolomic signatures of intravenous racemic ketamine associated remission in treatment-resistant depression: A pilot hypothesis generating study. Psychiatry Res. 2022 Aug;314:114655. doi: 10.1016/j.psychres.2022.114655. Epub 2022 May 28.

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