Kétamine, dépression et suicide : vers une nouvelle classe d’antidépresseurs ?

Résumé La kétamine, antagoniste NMDA utilisé en anesthésie, fait l’objet de recherches concernant son action antidépressive : cette revue de la littérature discute de son intérêt thérapeutique en psychiatrie. La kétamine a une action antidépressive rapide mais de durée transitoire à dose sub-anesthésique, avec des effets secondaires dissociatifs et cardiaques bénins. Il existerait une action spécifique et rapide sur les idées suicidaires. En modulant le métabolisme du glutamate, la kétamine stimulerait des systèmes neurotrophiques et entraînerait une neuroplasticité cérébrale accrue. Des actions anti-inflammatoires ou analgésiques seraient également impliquées. L’utilisation de la kétamine comme antidépresseur semble difficile à envisager de par son action brève et son profil de tolérance, mais cibler le système glutamatergique pourrait avoir une utilité en tant que traitement spécifique de la crise suicidaire. Objectives Major depressive disorder is a frequent and serious disease, which can result in suicide. Treatment resistance is frequent in this pathology and actual antidepressants need a few weeks before having a clinical efficacy. Ketamine is an NMDA antagonist used in anaesthesia for decades, and has shown since several years a fast and efficient antidepressant effect in patients with treatment-resistant depression. Methods The aim of this review is to investigate the state of the art of the scientific literature about the antidepressant effects of ketamine. Results A subanaesthetic infusion (0.2 mg/kg) of intravenous ketamine reduced depressive symptoms for both unipolar and bipolar depression in many randomized controlled trials. Clinical effects can be observed as soon as 4 hours after treatment and last for a few days, which has been confirmed in recent meta-analysis. This molecule could also potentiate the efficacy of electroconvulsive therapy and have a neuroprotective effect in such treatments however results are controversial. Ketamine also showed a fast and specific reduction of suicidal ideation. Mechanisms of action of ketamine are still poorly known. Its partial NMDA antagonist action modulates the metabolism of glutamate, and thus stimulates neurotropic systems such as BDNF or mTOR resulting in an increased brain neuroplasticity. Anti-inflammatory or analgesic effects may also explain ketamine's efficacy. This treatment can provoke dissociative effects and cardiovascular events which are reversible within a few hours. While promising, ketamine's efficacy has a limited duration in time. Conclusion Ketamine has a fast antidepressant effect in both resistant unipolar and bipolar depression. However it seems difficult to use it as an antidepressant in common practice due to its short duration of efficacy and adverse effects: studies are in progress to develop new molecules aiming the same molecular pathways. Ketamine could be a useful treatment of acute suicidal crisis in major depressive disorder and upcoming researches should help understanding its mechanisms of action as an antisuicidal medication. [ABSTRACT FROM AUTHOR]