The use of esketamine in the treatment of patients with severe depression and suicidal ideation: systematic review and meta-analysis.

INTRODUCTION Depression is a very common and disabling mental illness and can be assessed by applying several questionnaires, the most common being the Montgomery-Asberg rating scale1, scoring on a scale of 0–60, where 7–19 denotes mild depression, 20–34 moderate depression, and greater than 34 severe depression. Major or severe depression is commonly associated with suicidal ideation, resulting in a suicide attempt or suicide. Esketamine, the S-enantiomer of racemic ketamine, is an antidepressant with a novel mechanism of action. It is a nonselective, noncompetitive antagonist of the N-methyl-Daspartate receptor and the ionotropic glutamate receptor. It promotes increased stimulation of the α-amino-3-hydroxy5-methyl-4-isoxazole propionic acid receptor (AMPAR) and neurotrophic signaling, which restore brain synaptic function. However, the mechanism by which esketamine exerts its antidepressant effect is unknown. Unlike other antidepressant treatments, the primary antidepressant action of esketamine does not directly involve monoamine, GABA, or opioid receptors2. The aim of this systematic review was to evaluate the use of esketamine compared to placebo in patients with severe depression and suicidal ideation. CLINICAL DOUBT What is the efficacy and safety of using esketamine in the treatment of patients with severe depression and suicidal ideation?