Immunoregulation and antidepressant effect of ketamine

Zhang, Nan; Yao, Lihua; Wang, Peilin; Liu, Zhongchun

doi:10.1515/tnsci-2020-0167

Cited by 16 publications

(10 citation statements)

References 107 publications

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“…The activation of the immune system is associated with depression and the anti-inflammatory effect of antidepressant treatment is related to response [ 75 ]. A recent meta-analysis revealed that antidepressant treatment was related to a significant TNF-α decrease in responders [ 50 ].…”

Section: Resultsmentioning

confidence: 99%

The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine

Wilkowska

Cubała

2022

IJMS

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Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism.

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Section: Resultsmentioning

confidence: 99%

The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine

Wilkowska

Cubała

2022

IJMS

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“…In addition, the immunoregulatory effects of esketamine may interact with the affected and closely linked immune and nervous system in CPRS patients [ 7 , 50 ]. For instance, recent studies on depression and comorbid pain described the immunoregulatory aspects of esketamine that may result in downregulation of peripheral pro-inflammatory cytokines and the attenuation of central glial cells [ 8 , 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2)

Mangnus

Dirckx

Bharwani

et al. 2023

BMC Musculoskelet Disord

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Background Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed. Methods In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient. Discussion If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment. Trial registration ClinicalTrials.gov Identifier NCT05212571, date of registration 01-28-2022. Protocol version: Version 3, February 2022.

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“…In line with previous studies, ketamine exerts its antidepressant effects by modulating the immune system, including peripheral inflammatory cytokines, central microglia, and astrocytes. 44 Furthermore, the GO enrichment analysis of 113 mRNAs in the ceRNA network unveiled a predominant involvement of these mRNAs in biological processes associated with drug transport. Drug transport is the kinetic process of the absorption, distribution, metabolism and excretion of drugs from the body.…”

Section: Discussionmentioning

confidence: 99%

The effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice

Zhang,

Ma,

Lin

et al. 2023

Hum Exp Toxicol

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Objective This study aimed to investigate the impact of esketamine on the intestinal flora and microenvironment in mice using mRNA transcriptome sequencing and 16S rRNA sequencing. Methods Ten female mice were randomly assigned to two groups. One group received daily intramuscular injections of sterile water, while the other group received esketamine. After 24 days, the mice were sacrificed, and their intestinal tissues and contents were collected for 16S rRNA sequencing and mRNA transcriptome sequencing. The intergroup differences in the mouse intestinal flora were analyzed. Differentially expressed genes were utilized to construct ceRNA networks and transcription factor regulatory networks to assess the effects of esketamine on the intestinal flora and intestinal tissue genes. Results Esketamine significantly altered the abundance of intestinal microbiota, including Adlercreutzia equolifaciens and Akkermansia muciniphila. Differential expression analysis revealed 301 significantly upregulated genes and 106 significantly downregulated genes. The ceRNA regulatory network consisted of 6 lncRNAs, 44 miRNAs, and 113 mRNAs, while the regulatory factor network included 13 transcription factors and 53 target genes. Gene Ontology enrichment analysis indicated that the differentially expressed genes were primarily associated with immunity, including B-cell activation and humoral immune response mediation. The biological processes in the ceRNA regulatory network primarily involved transport, such as organic anion transport and monocarboxylic acid transport. The functional annotation of target genes in the TF network was mainly related to epithelial cells, including epithelial cell proliferation and regulation. Conclusion Esketamine induces changes in gut microbiota and the intestinal microenvironment, impacting the immune environment and transport modes.

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Immunoregulation and antidepressant effect of ketamine

Cited by 16 publications

References 107 publications

The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine

The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2)

The effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice

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