Antisuicidal effect, BDNF Val66Met polymorphism, and low-dose ketamine infusion: Reanalysis of adjunctive ketamine study of Taiwanese patients with treatment-resistant depression (AKSTP-TRD)

Chen, Mu Hong; Lin, Wei Chen; Wu, Hui; Cheng, Chih Ming; Li, Cheng Ta; Chen, Hong; Tu, Pei Chi; Bai, Ya Mei; Tsai, Shih‐Jen; Su, Tung Ping

doi:10.1016/j.jad.2019.03.075

Cited by 46 publications

(23 citation statements)

References 23 publications

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“…Interestingly, patients with a Val66Met single-nucleotide polymorphism associated with impairments in BDNF release and mRNA trafficking were also found to have reduced responses to ketamine. 115,116 In a study of three depressed patients responding to ketamine, the authors observed an increase in expression of plasma mTOR and eEF2 phosphorylation. 117 While the increase in mTOR is supported by animal studies, it was surprising to note an increase in eEF2 phosphorylation that was previously shown to be reduced in animal models.…”

Section: Antidepressant Mechanisms Of Ketamine and Potential Biochemimentioning

confidence: 99%

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Matveychuk

Thomas

Swainson

et al. 2020

Therapeutic Advances in Psychopharmacology

108

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Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s effects on the brain. Of particular interest and therapeutic potential is the ability of ketamine to exert rapid antidepressant properties as early as several hours after administration. This is in stark contrast to the delayed effects observed with traditional antidepressants, often requiring several weeks of therapy for a clinical response. Furthermore, ketamine appears to have a unique mechanism of action involving glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and [Formula: see text]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity. This paper provides a brief overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers (biochemical, inflammatory, metabolic, neuroimaging sleep-related and cognitive) for predicting response to and/or monitoring of therapeutic outcome with ketamine.

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Section: Antidepressant Mechanisms Of Ketamine and Potential Biochemimentioning

confidence: 99%

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Matveychuk

Thomas

Swainson

et al. 2020

Therapeutic Advances in Psychopharmacology

108

View full text Add to dashboard Cite

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“…26 Chen et al found that the BDNF Val66Met polymorphism may predict the antisuicidal response to a single ketamine infusion. 4 Similarly, the findings of studies exploring the association of BDNF and the antidepressant effects of single ketamine infusions were also mixed. 39,40 For instance, Haile et al found that plasma levels of BDNF at 240 min after a single ketamine infusion were strongly and negatively correlated with MADRS scores at 240 min.…”

Section: Discussionmentioning

confidence: 99%

“…3 Up to 66% of depressed patients suffer from suicidal ideation at some point, and depressed patients are approximately 20 times more likely to die by suicide than the general population. 1,4 However, treatment strategies for depressed patients with acute suicidal ideation and behavior are limited. 5,6 Although numerous studies have found that serotonin and norepinephrine reuptake inhibitors, 7 selective serotonin reuptake inhibitors, 8 and mood stabilizers (e.g.…”

Section: Introductionmentioning

confidence: 99%

Association between plasma levels of BDNF and the antisuicidal effects of repeated ketamine infusions in depression with suicidal ideation

Zheng

Zhou

Wang

et al. 2020

Therapeutic Advances in Psychopharmacology

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Background: This study is the first to examine the association between plasma levels of brain-derived neurotrophic factor (BDNF) and the antisuicidal effects of repeated ketamine infusions in depressed patients with suicidal ideation. Methods: Fifty-seven depressed patients with suicidal ideation received six ketamine infusions (0.5 mg/kg) during a 12 days period. Suicidality was measured with the Scale for Suicidal Ideations (SSI-part 1), item 10 of the Montgomery–Åsberg Depression Rating Scale (MADRS), and item 3 of the Hamilton Depression Rating Scale (HAMD) at baseline, 1 day after the first infusion (1 day), 1 day after the sixth infusion (13 days), and at 2 weeks after the last infusion (26 days). Plasma levels of BDNF were measured by enzyme-linked immunosorbent assay at baseline, 13 days, and 26 days. Results: Overall, 46 (80.7%) depressed patients with suicidal ideation had an antisuicidal response at 13 days. Despite a significant reduction in suicidal symptoms over time, no changes in plasma levels of BDNF were found after ketamine treatment when compared with baseline. Correlation analysis showed that no significant association was observed between the plasma levels of BDNF and the changes in the severity of suicidal symptoms as measured by SSI-part 1, item 10 of the MADRS, or item 3 of the HAMD at 1 day, 13 days, and 26 days (all p < 0.05). Conclusion: Our results indicated that plasma levels of BDNF may not serve as a biomarker for determining the antisuicidal effects of six ketamine infusions in depressed patients with suicidal ideation.

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“…Most reliably the intensity of dissociative experiences as assessed by the Clinician-Administered Dissociative States Scale during administration has been found to correlate positively with subsequent antidepressant effect [20]. Nonreplicated outcomes have found a negative correlation of response with anxiety during administration [21], correlations with quantitative EEG [22][23][24] and polysomnography parameters [25] as well as an influence of the BDNF Val66Met polymorphism [26]. Neither gender nor age appear to influence antidepressant treatment response [27].…”

Section: Response Predictionmentioning

confidence: 99%

Ketamine in the Treatment of Depressive Episodes

2019

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The treatment of depressive episodes remains complicated by the long latency of antidepressant efficacy, insufficient response, and high risk of suicide. Ketamine and esketamine have been proposed as fast-acting substances able to overcome these impediments.Since the first randomized controlled trial in the year 2000, numerous studies have explored the antidepressant efficacy of ketamine and esketamine. Clear evidence has emerged that a single infusion exerts a significant antidepressant and antisuicidal effect in both unipolar and bipolar depression. A few studies suggest that antidepressant response can be improved and maintained by repeated administration. Although intravenous application has been most common, subcutaneous, intramuscular, and intranasal application has also been successful. There is some evidence that ketamine may accelerate the response to electroconvulsive therapy without improving the overall response rate.The precise position of ketamine and esketamine within treatment algorithms have yet to be defined, and issues surrounding potential toxicity need to be resolved.

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Antisuicidal effect, BDNF Val66Met polymorphism, and low-dose ketamine infusion: Reanalysis of adjunctive ketamine study of Taiwanese patients with treatment-resistant depression (AKSTP-TRD)

Cited by 46 publications

References 23 publications

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Association between plasma levels of BDNF and the antisuicidal effects of repeated ketamine infusions in depression with suicidal ideation

Ketamine in the Treatment of Depressive Episodes

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