Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Baltimore, MD, USA.
⁴ Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Veterans Affairs Maryland Health Care System, Baltimore, MD, USA.
⁶ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, NIMH-NIH, Bethesda, MD, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Department of Psychological and Brain Sciences, and Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: fgoes1@jhmi.ed.

PMID: 37625426
PMCID: PMC11534374
DOI: 10.1016/S2215-0366(23)00183-9

Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies

Gustavo C Medeiros et al. Lancet Psychiatry. 2023 Oct.

. 2023 Oct;10(10):790-800.

doi: 10.1016/S2215-0366(23)00183-9. Epub 2023 Aug 22.

Authors

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
² Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Baltimore, MD, USA.
⁴ Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Veterans Affairs Maryland Health Care System, Baltimore, MD, USA.
⁶ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, NIMH-NIH, Bethesda, MD, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Department of Psychological and Brain Sciences, and Center for Psychedelic and Consciousness Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: fgoes1@jhmi.ed.

PMID: 37625426
PMCID: PMC11534374
DOI: 10.1016/S2215-0366(23)00183-9

Abstract

Ketamine is an effective antidepressant, but there is substantial variability in patient response and the precise mechanism of action is unclear. Neuroimaging can provide predictive and mechanistic insights, but findings are limited by small sample sizes. This systematic review covers neuroimaging studies investigating baseline (pre-treatment) and longitudinal (post-treatment) biomarkers of responses to ketamine. All modalities were included. We performed searches of five electronic databases (from inception to April 26, 2022). 69 studies were included (with 1751 participants). There was substantial methodological heterogeneity and no well replicated biomarker. However, we found convergence across some significant results, particularly in longitudinal biomarkers. Response to ketamine was associated with post-treatment increases in gamma power in frontoparietal regions in electrophysiological studies, post-treatment increases in functional connectivity within the prefrontal cortex, and post-treatment increases in the functional activation of the striatum. Although a well replicated neuroimaging biomarker of ketamine response was not identified, there are biomarkers that warrant further investigation.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests GSS conducted an investigator-initiated study that used medication (vortioxetine) provided without charge by Lundbeck. TDG is listed as coauthor on patent and patent applications related to the pharmacology and use of (2R,6R)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the University of Maryland, Baltimore, but will share a percentage of any royalties that might be received. TDG has also received research funding from Allergan and Roche Pharmaceuticals. 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 (2R,6R)-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 (2R,6R)-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 US Government but will share a percentage of any royalties that might be received. FSB is a scientific adviser for WavePaths, and MindState Design Labs. FSG has received research grant support from Janssen Therapeutics. All other authors declare no competing interests.

Figures

**Figure 1.**
PRISMA flow diagram of systematic searches for studies assessing neuroimaging biomarkers of antidepressant response to ketamine/esketamine ^a Databases used in the searches: Medline (PubMed), Cochrane Library, Embase, PsycInfo, and Web of Science. ^b Hand searching included screening of review articles, grey literature, included papers and manuscripts that cited the included papers.

See this image and copyright information in PMC

References

1. Collaborators GMD. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet Psychiatry 2022; 9(2): 137–50. - PMC - PubMed
1. McIntyre RS, Rosenblat JD, Nemeroff CB, et al. Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: an international expert opinion on the available evidence and implementation. American Journal of Psychiatry 2021; 178(5): 383–99. - PMC - PubMed
1. Malhi GS, Mann JJ. Depression. The Lancet 2018; 392(10161): 2299–312. - PubMed
1. Medeiros GC, Gould TD, Prueitt WL, et al. Blood-based biomarkers of antidepressant response to ketamine and esketamine: A systematic review and meta-analysis. Molecular psychiatry 2022: 1–12. - PMC - PubMed
1. Niciu MJ, Luckenbaugh DA, Ionescu DF, et al. Clinical predictors of ketamine response in treatment-resistant major depression. The Journal of clinical psychiatry 2014; 75(5): e417. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies

Affiliations

Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous