Pharmacopsychiatry 2022; 55(03): 170
DOI: 10.1055/s-0042-1747662
Abstracts | XIVth Symposium of the Task Force Therapeutic Drug Monitoring of the AGNP

Ketamine Metabolite Plasma Levels as Potential Blood Markers of Ketamine Efficacy in Treatment Resistant Depression

M. Spangemacher
1   Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
2   Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
J. Reinwald
2   Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
3   Department of Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
M. Böttcher
4   MVZ Medical Laboratories Dessau Kassel GmbH
,
M. Gilles
2   Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
M. Walter
5   Department of Psychiatry and Psychotherapy, Medical Faculty Tuebingen, University of Tuebingen Germany
,
A. Sartorius
2   Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
3   Department of Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
G. Gründer
1   Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
› Author Affiliations
› Further Information
Also available at
 

Introduction Accumulating evidence has revealed robust fast-acting antidepressant effects of ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, in patients with treatment-resistant depression (TRD). However, considering that clinical responses can only be observed in 50% of TRD patients [1], treatment decisions lack predictors on patients’ individual benefit.

Even though ketamine and norketamine plasma concentrations did not correlate with the acute effects or the immediate antidepressant effects of ketamine [2], there seem to be more and more indications that the metabolites (f.e. hydroxyketamine) could be essential for the prediction of its long-term antidepressant effects [3].

In this study, (R,S)-ketamine metabolite plasma concentrations will be examined as a potential blood biomarker for treatment response in the course of the NeuroMarKet (Neuroimaging and Blood Markers as Indicators of Ketamine Efficacy in Treatment Resistant Depression) study.

Methods NeuroMarKet aims to acquire data from 1) a large multimodal patient sample and 2) a parallel animal study with harmonized observation time points. Centralized analyses of specimen will include combined blood biomarkers of peripheral proteomics, BDNF levels, acetylated alphat-ubulin, and ketamine metabolites with non-invasive functional MRI markers and electrophysiology.

TRD patients will receive six ketamine injections. Blood, as well as brain biomarkers, will be assessed 24 hours later and compared to a baseline measurement before the injection.

Plasma levels of ketamine, its enantiomers and its metabolites will be measured at baseline, one hour after injection, 24 hours later and directly before the next injection at all six injection time points.



Publication History

Article published online:
16 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Schwartz J., Murrough J.W., Iosifescu D.v.. Ketamine for treatment-resistant depression: recent developments and clinical applications. Evidence-Based Mental Health 2016; 19 (02) 35-38
    CrossrefPubMedGoogle Scholar
  • 2 Zarate C.A., Brutsche N., Laje G., Luckenbaugh D.A., Venkata S.L.V., Ramamoorthy A., Moaddel R., Wainer I.W.. Relationship of Ketamine’s Plasma Metabolites with Response, Diagnosis, and Side Effects in Major Depression. Biological Psychiatry 2012; 72 (04) 331
    CrossrefPubMedGoogle Scholar
  • 3 Zanos P., Moaddel R., Morris P.J., Riggs L.M., Highland J.N., Georgiou P., Pereira E.F.R., Albuquerque E.X., Thomas C.J., Zarate C.A., Gould T.D. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacological Reviews 2018; 70 (03) 621-660
    CrossrefPubMedGoogle Scholar