La prise en charge médicamenteuse de la dépression se heurte aux limites des traitements antidépresseurs conventionnels que sont leur délai d’action et le pourcentage non négligeable de patients résistants aux stratégies thérapeutiques proposées. La prise en charge de ces dépressions résistantes est un enjeu de santé publique majeur. Depuis quelques années, la découverte d’un effet antidépresseur rapide et puissant de la kétamine, antagoniste non compétitif du récepteur NMDA au glutamate, a conduit à un nombre grandissant d’études sur cette nouvelle voie thérapeutique originale et prometteuse. Cette revue de la littérature a pour but de faire la synthèse des différents essais cliniques ayant mis en évidence cette propriété de la kétamine ainsi que des potentielles indications thérapeutiques et modalités d’utilisations.

Depressive disorders have a major impact on public health. They are prevalent and disabling, with high economic burden for society. Antidepressants have a delayed action and at least one third of patients do not achieve adequate response. The recent discovery of ketamine's unique antidepressant properties, with rapid onset of response and high rate of responders opens new perspectives for treatment-resistant depression (TRD).

The aim of this article is to summarize preclinical trials and clinical trials demonstrating ketamine antidepressant properties and to review the different modalities of use.

Most clinical studies used ketamine with a single subanesthetic intravenous administration in patients with treatment-resistant depression, demonstrating a rapid but transient antidepressant response with high response rates. To prevent relapse and maintain the initial benefits, few studies have shown the interest of serial infusions of ketamine, while others combined ketamine and electroconvulsive therapy using the former as an anesthetic. So far, relay treatments with glutamatergic agents such as riluzole are disappointing. Although most studies were conducted in patients with TRD in recurrent depression or bipolar disorder, efficacy in acutely suicidal patients is promising.

Our review highlights the increasing interest in the use of ketamine in the treatment of treatment-resistant depression. Although a widespread use of ketamine as an antidepressant in routine clinical settings seems limited by psychotomimetic effects and the lack of strategy to maintain initial benefits, ketamine or related drugs might be used to target specific conditions, such as bipolar depression or high suicide risk.