Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes

Réus, Gislaine Z.; Matias, Beatriz I.; Maciel, Amanda L.; Abelaira, Helena M.; Ignácio, Zuleide Maria; Moura, Airam B. de; Matos, Danyela; Danielski, Lucinéia Gainski; Petronilho, Fabrícia; Carvalho, André F.; Quevedo, Joao L De

doi:10.1016/j.pharep.2017.04.021

Cited by 17 publications

(9 citation statements)

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“…High level of proteins and lipid peroxidation and an imbalance between superoxide dismutase and catalase were found in the brain and in the submitochondrial particles into the brain, and the antidepressant treatment improves these oxidative stress parameters in patients with depression [14]. Higher serum total oxidant status and a lower serum total antioxidant capacity in depressed patients were reversed after treatment with antidepressants in animal models of depression as well as in patients [15][16][17].…”

Section: Introductionmentioning

confidence: 98%

Major Depressive Disorder and Oxidative Stress: In Silico Investigation of Fluoxetine Activity against ROS

et al. 2019

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Major depressive disorder is a psychiatric disease having approximately a 20% lifetime prevalence in adults in the United States (U.S.), as reported by Hasin et al. in JAMA Psichiatry 2018 75, 336–346. Symptoms include low mood, anhedonia, decreased energy, alteration in appetite and weight, irritability, sleep disturbances, and cognitive deficits. Comorbidity is frequent, and patients show decreased social functioning and a high mortality rate. Environmental and genetic factors favor the development of depression, but the mechanisms by which stress negatively impacts on the brain are still not fully understood. Several recent works, mainly published during the last five years, aim at investigating the correlation between treatment with fluoxetine, a non-tricyclic antidepressant drug, and the amelioration of oxidative stress. In this work, the antioxidant activity of fluoxetine was investigated using a computational protocol based on the density functional theory approach. Particularly, the scavenging of five radicals (HO•, HOO•, CH3OO•, CH2=CHOO•, and CH3O•) was considered, focusing on hydrogen atom transfer (HAT) and radical adduct formation (RAF) mechanisms. Thermodynamic as well as kinetic aspects are discussed, and, for completeness, two metabolites of fluoxetine and serotonin, whose extracellular concentration is enhanced by fluoxetine, are included in our analysis. Indeed, fluoxetine may act as a radical scavenger, and exhibits selectivity for HO• and CH3O•, but is inefficient toward peroxyl radicals. In contrast, the radical scavenging efficiency of serotonin, which has been demonstrated in vitro, is significant, and this supports the idea of an indirect antioxidant efficiency of fluoxetine.

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Section: Introductionmentioning

confidence: 98%

Major Depressive Disorder and Oxidative Stress: In Silico Investigation of Fluoxetine Activity against ROS

et al. 2019

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“…Ketamine, an N -methyl-D-aspartate receptor antagonist, has shown potent anti-inflammatory effects in various models of systemic inflammation, including endotoxemia, ischemia, and burns. 12 , 13 These effects were observed in multiple organ systems and involve the modulation of certain molecular mediators of the inflammatory response. 14 In addition, when administered either before or after various pro-inflammatory responses, ketamine was found to diminish systemic production of cytokines and improve survival.…”

Section: Introductionmentioning

confidence: 99%

Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway

Liang¹,

Wu²,

Xie³

et al. 2018

DDDT

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BackgroundKetamine can act as a multifunctional neuroprotective agent by inhibiting oxidative stress, cellular dysfunction, and apoptosis. Although it has been proven to be effective in various neurologic disorders, the mechanism of the treatment of traumatic brain injury (TBI) is not fully understood. The aim of this study was to investigate the neuroprotective function of ketamine in models of TBI and the potential role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in this putative protective effect.Materials and methodsWild-type male mice were randomly assigned to five groups: Sham group, Sham + ketamine group, TBI group, TBI + vehicle group, and TBI + ketamine group. Marmarou’s weight drop model in mice was used to induce TBI, after which either ketamine or vehicle was administered via intraperitoneal injection. After 24 h, the brain samples were collected for analysis.ResultsKetamine significantly ameliorated secondary brain injury induced by TBI, including neurological deficits, brain water content, and neuronal apoptosis. In addition, the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were restored by the ketamine treatment. Western blotting and immunohistochemistry showed that ketamine significantly increased the level of Nrf2. Furthermore, administration of ketamine also induced the expression of Nrf2 pathway-related downstream factors, including hemeoxygenase-1 and quinine oxidoreductase-1, at the pre- and post-transcriptional levels.ConclusionKetamine exhibits neuroprotective effects by attenuating oxidative stress and apoptosis after TBI. Therefore, ketamine could be an effective therapeutic agent for the treatment of TBI.

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“…Rats treated with fluoxetine or lamotrigine or these drugs together with ketamine had smaller lipid peroxidation compared with the ketamine group. The authors suggest that lamotrigine and fluoxetine protect mice brain cells from oxidative damage caused by ketamine [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…After analyzing the identified studies on ketamine and lamotrigine combination, we conclude that it is not possible to answer any of the stated questions. Preclinical studies suggest the possibility that lamotrigine could potentiate the effect of ketamine on neuroplasticity and synapse strength, augment the antidepressant effect of ketamine, and reduce lipid damage in the hippocampus [ 40 , 41 ]. The downregulation of AA cascade may increase the activity of AMPA receptors.…”

Section: Discussionmentioning

confidence: 99%

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Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

Wilkowska

Wiglusz

Jakuszkowiak-Wojten

et al. 2022

Cells

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Background and Objectives: Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented. Materials and Methods: PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied. Results: Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms. Conclusions: The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine’s side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine–lamotrigine combination in bipolar patients.

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Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes

Abstract: In conclusion, ketamine induced antioxidant or pro-antioxidant effects dependent of antidepressant classes or brain area.

Cited by 17 publications

References 62 publications

Major Depressive Disorder and Oxidative Stress: In Silico Investigation of Fluoxetine Activity against ROS

Major Depressive Disorder and Oxidative Stress: In Silico Investigation of Fluoxetine Activity against ROS

Ketamine ameliorates oxidative stress-induced apoptosis in experimental traumatic brain injury via the Nrf2 pathway

Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review

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