Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study

Chen, Mu Hong; Li, Cheng Ta; Lin, Wei Chen; Chen, Hong; Tu, Pei Chi; Bai, Ya Mei; Cheng, Chih Ming; Su, Tung Ping

doi:10.1016/j.psychres.2018.08.078

Cited by 113 publications

(88 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In line with our expectations, the levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were decreased after the ketamine infusions in our study, which is consistent with the results of previous studies [31][32][33][34] that administered a single infusion in patients with depression. We found that changes in the IL-6 and IL-17A levels were significantly negatively associated with the antidepressant response.…”

Section: Cytokines and Treatment Responsesupporting

confidence: 93%

“…Changes in inflammatory cytokines after a single ketamine infusion in depression have been demonstrated previously 31,33,34 , while the effect on immunity of repeated infusions has been rarely reported. In this study, we conducted an open-label clinical trial of six ketamine infusions in patients with depression and examined multiple inflammatory cytokines throughout the treatment period.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder

et al. 2020

View full text Add to dashboard Cite

Increasing evidence has demonstrated that inflammatory cytokines play an important role in major depressive disorder (MDD) and are associated with treatment outcomes. Few studies have explored the trajectories of multiple inflammatory cytokines after repeated ketamine infusions in MDD. In this study, we conducted a secondary analysis to investigate the impact of ketamine on the modulation of the inflammatory pathway in depression and whether this pathway contributes to the antidepressant properties of ketamine. A total of 60 patients with depression received six ketamine infusions (0.5 mg/kg) during a 12-day period. The Montgomery-Asberg Scale (MADRS) was administered, and blood samples were collected at baseline and 24 h and 14 days after the sixth infusion (days 0, 13, and 26). Plasma levels of the 19 cytokines were measured using the Luminex assay. At baseline, inflammatory cytokines were associated with the severity of depression. The concentrations of pro-and anti-inflammatory factors, including granulocyte macrophage colony-stimulating factor (GM-CSF), fractalkine, interferon gamma (IFN-γ), interleukin (IL)-10, IL-12p70, IL-17A, IL-1β, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, and tumor necrosis factor alpha (TNF-α), were downregulated after repeated ketamine administration (all p < 0.05). In addition, alterations in the levels of IL-17A (r = −0.259, p = 0.046) and IL-6 (r = −0.262, p = 0.043) were correlated with symptom improvement. A lower level of interferon-inducible T cell alpha chemoattractant (ITAC) at baseline was predictive of ketamine treatment response on day 13 according to a stepwise linear regression analysis (β = −0.296, p = 0.040). Our results suggest that the inflammatory pathway may be involved in the antidepressant effects of ketamine, which may be conducive to future treatment strategy optimization.

show abstract

Section: Cytokines and Treatment Responsesupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In 2015, we reported that baseline interleukin‐6 (IL‐6) could be a predictive blood biomarker for the rapid antidepressant effects of ketamine . Furthermore, there is a positive correlation between the decrease in levels of tumor necrosis factor‐α 40 min post‐injection of ketamine and ketamine’s antidepressant actions . Thus, the rapid anti‐inflammatory actions of ketamine might contribute to its rapid antidepressant effects.…”

Section: Ketamine’s Antidepressant Effects In Humansmentioning

confidence: 99%

Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective

Hashimoto

2019

Psychiatry Clin Neurosci

263

193

View full text Add to dashboard Cite

Major depressive disorder (MDD) is one of the most disabling psychiatric disorders. Approximately one‐third of the patients with MDD are treatment resistant to the current antidepressants. There is also a significant therapeutic time lag of weeks to months. Furthermore, depression in patients with bipolar disorder (BD) is typically poorly responsive to antidepressants. Therefore, there exists an unmet medical need for rapidly acting antidepressants with beneficial effects in treatment‐resistant patients with MDD or BD. Accumulating evidence suggests that the N‐methyl‐D‐aspartate receptor (NMDAR) antagonist ketamine produces rapid and sustained antidepressant effects in treatment‐resistant patients with MDD or BD. Ketamine is a racemic mixture comprising equal parts of (R)‐ketamine (or arketamine) and (S)‐ketamine (or esketamine). Because (S)‐ketamine has higher affinity for NMDAR than (R)‐ketamine, esketamine was developed as an antidepressant. On 5 March 2019, esketamine nasal spray was approved by the US Food and Drug Administration. However, preclinical data suggest that (R)‐ketamine exerts greater potency and longer‐lasting antidepressant effects than (S)‐ketamine in animal models of depression and that (R)‐ketamine has less detrimental side‐effects than (R,S)‐ketamine or (S)‐ketamine. In this article, the author reviews the historical overview of the antidepressant actions of enantiomers of ketamine and its major metabolites norketamine and hydroxynorketamine. Furthermore, the author discusses the other potential rapid‐acting antidepressant candidates (i.e., NMDAR antagonists and modulators, low‐voltage‐sensitive T‐type calcium channel inhibitor, potassium channel Kir4.1 inhibitor, negative modulators of γ‐aminobutyric acid, and type A [GABAA] receptors) to compare them with ketamine. Moreover, the molecular and cellular mechanisms of ketamine’s antidepressant effects are discussed.

show abstract

“…75 One study has shown rapid decreases in levels of IL-6 and TNF-α, as well as a correlation between the decrease in TNF-α and a reduction in the Montgomery Asberg Depression Rating Scale (MADRS) score. 76 Another study found that ketamine influences the kynurenine pathway by increasing the level of kynurenine, kynurenic acid and decreases the level of quinolinic acid acting as a rapid anti-inflammatory agent in patients with bipolar depression. 77 No significant correlation has been found between the levels of inflammatory markers (C-reactive protein and intracellular adhesion molecule-1), before or after ketamine infusion in BD patients.…”

Section: Immunological Effectsmentioning

confidence: 99%

<p>Ketamine in Bipolar Disorder: A Review</p>

Wilkowska¹,

Szałach²,

Cubała³

2020

NDT

View full text Add to dashboard Cite

Bipolar disorder (BD) is a psychiatric illness associated with high morbidity, mortality and suicide rate. It has neuroprogressive course and a high rate of treatment resistance. Hence, there is an unquestionable need for new BD treatment strategies. Ketamine appears to have rapid antidepressive and antisuicidal effects. Since most of the available studies concern unipolar depression, here we present a novel insight arguing that ketamine might be a promising treatment for bipolar disorder.

show abstract

Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study

Cited by 113 publications

References 21 publications

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder

Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective

<p>Ketamine in Bipolar Disorder: A Review</p>

Contact Info

Product

Resources

About