Citation

Olié E, Lengvenyte A, Courtet P. Biol. Aujourdhui 2023; 217(3-4): 157-160.

Vernacular Title

Comment la kétamine peut-elle aider à mieux prendre en charge le risque suicidaire ?

Copyright

(Copyright © 2023, La Société de biologie)

DOI

10.1051/jbio/2023029

PMID

38018943

Abstract

In France, suicidal behaviors remain a major public health issue. Depressed patients with suicidal ideation have more severe depressive symptoms, a more unfavorable disease course, and a greater number of suicide attempts than patients without suicidal ideation. Unfortunately, conventional antidepressants tend to be less effective in patients with suicidal tendencies than in those without. Nevertheless, promising advancements have emerged with the use of ketamine, which has shown significant and rapid efficacy in reducing the intensity of suicidal ideation in depressed patients within the first 72 h after its administration. Several mechanisms are potentially involved: (1) reduction of anhedonia. It has been demonstrated that ketamine reduces both anhedonia and suicidal ideation. In depressed patients, the reduction of anhedonia observed 2 h after ketamine administration is associated with metabolic changes in the anterior cingulate cortex involved in suicidal ideation; (2) activation of neuroplasticity cascades. The reduction in suicidal ideation within 24 h following ketamine administration is correlated with changes in plasma BDNF levels and is modulated by the Val66Met functional polymorphism of the BDNF gene. Moreover, preclinical and clinical studies have shown that ketamine induces functional and connectivity changes in the prefrontal and anterior cingulate regions, which are strongly implicated in suicidal behaviors; (3) reduction of inflammation. It is now widely accepted that suicidal behaviors are associated with low-grade inflammation, and with elevated quinolinic acid and reduced kynurenic acid levels. Interestingly, predictors of a reduction in suicidal ideation after ketamine infusion include initial severity of suicidal thoughts and depression, as well as baseline blood levels of kynurenic acid; (4) involvement of the opioidergic system. Post-mortem studies have indicated alterations in the opioidergic system related to suicidal behaviors. A recent study suggested that the antisuicidal effect of ketamine may depend on this system because naltrexone, an antagonist of mu opioid receptors, abolished the typical antidepressant effect and reduction in suicidal ideation observed following ketamine administration. In conclusion, ketamine exhibits promising potential in mitigating suicidal ideation - its effects are specific, rapid, albeit temporary. The suggested mechanisms driving its efficacy are multifaceted. Nevertheless, it is yet to be determined whether ketamine administration can effectively prevent suicidal behaviors.

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Les patients souffrant de dépression suicidaire répondent moins bien aux traitements antidépresseurs conventionnels que ceux qui n'ont pas d'idées suicidaires. Une avancée prometteuse dans ce domaine est l'utilisation de la kétamine, qui a montré une efficacité significative et rapide dans la réduction de l'intensité des idées suicidaires chez les patients déprimés. Des études ont montré qu'une seule perfusion intraveineuse de kétamine à faible dose pouva3it réduire de manière significative et durable les idées de suicide. De plus, la kétamine semble également réduire l'anhédonie, un symptôme associé aux idées suicidaires. Les mécanismes d'action de la kétamine sont multiples. Elle stimule la neuroplasticité via l'activation de la voie du BDNF (facteur neurotrophique du cerveau) et réduit l'inflammation. De plus, la kétamine semble agir sur le système opioïdergique, qui est impliqué dans les conduites suicidaires. En conclusion, la kétamine présente un intérêt dans la réduction des idées suicidaires chez les patients déprimés. Cependant, il est nécessaire de déterminer si son administration permet de prévenir les actes suicidaires. De plus amples recherches sont nécessaires pour mieux comprendre les mécanismes d'action de la kétamine et développer des stratégies thérapeutiques ciblées pour prévenir les conduites suicidaires.

Language: fr

Keywords

Humans; Suicidal Ideation; suicidal ideation; suicidal behavior; *Ketamine/adverse effects; Inflammation; ketamine; *Depressive Disorder, Major/drug therapy; Anhedonia; Antidepressive Agents/adverse effects; Brain-Derived Neurotrophic Factor/therapeutic use; conduites suicidaires; kétamine; Kynurenic Acid/therapeutic use