Personalized use of ketamine and esketamine for treatment-resistant depression.

Autor: Medeiros GC; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. gustavo.medeiros@som.umaryland.edu.; Advanced Depression Treatment (ADepT) Center, University of Maryland School of Medicine, Baltimore, MD, USA. gustavo.medeiros@som.umaryland.edu., Demo I; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Goes FS; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Zarate CA Jr; Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, NIMH-NIH, Bethesda, MD, USA., Gould TD; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.; Advanced Depression Treatment (ADepT) Center, University of Maryland School of Medicine, Baltimore, MD, USA.; Departments of Pharmacology and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.; Veterans Affairs Maryland Health Care System, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Nov 29; Vol. 14 (1), pp. 481. Date of Electronic Publication: 2024 Nov 29.
DOI: 10.1038/s41398-024-03180-8
Abstrakt: A large and disproportionate portion of the burden associated with major depressive disorder (MDD) is due to treatment-resistant depression (TRD). Intravenous (R,S)-ketamine (ketamine) and intranasal (S)-ketamine (esketamine) are rapid-acting antidepressants that can effectively treat TRD. However, there is variability in response to ketamine/esketamine, and a personalized approach to their use will increase success rates in the treatment of TRD. There is a growing literature on the precision use of ketamine in TRD, and the body of evidence on esketamine is still relatively small. The identification of reliable predictors of response to ketamine/esketamine that are easily translatable to clinical practice is urgently needed. Potential clinical predictors of a robust response to ketamine include a pre-treatment positive family history of alcohol use disorder and a pre-treatment positive history of clinically significant childhood trauma. Pre-treatment versus post-treatment increases in gamma power in frontoparietal brain regions, observed in electroencephalogram (EEG) studies, is a promising brain-based biomarker of response to ketamine, given its time of onset and general applicability. Blood-based biomarkers have shown limited usefulness, with small-effect increases in brain-derived neurotrophic factor (BDNF) being the most consistent indicator of ketamine response. The severity of treatment-emergent dissociative symptoms is typically not associated with a response either to ketamine or esketamine. Future studies should ensure that biomarkers and clinical variables are obtained in a similar manner across studies to allow appropriate comparison across trials and to reduce the signal-to-noise ratio. Most predictors of response to ketamine/esketamine have modest effect sizes; therefore, the use of multivariate predictive models will be needed.
Competing Interests: Competing interests: GCM, ID, FSG, CAZ, and TDG have no consulting or grant funding to disclose in the prior 3 years. TDG was supported by NIH/NIMH R01MH107615 and U.S. Department of Veterans Affairs Merit Awards 1I01BX004062 and 1I01BX006018. Funding for this work was provided in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIAMH002857). The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs, the National Institutes of Health, the Department of Health and Human Services, or the United States Government. TDG is listed as an inventor in patents and patent applications related to the pharmacology and use of a ketamine metabolites, including (2 R,6 R)-hydroxynorketamine, in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. TDG has assigned his patent rights to the University of Maryland, Baltimore, but will share a percentage of any royalties that may be received by the University of Maryland, Baltimore. CAZ is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2 R,6 R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2 R,6 R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government.
(© 2024. The Author(s).)
Databáze: MEDLINE
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