A network meta-analysis of 72 randomized controlled trials with 12,105 participants found that electroconvulsive therapy (ECT), ketamine, esketamine, and psilocybin are superior first-line treatments for treatment-resistant depression (TRD) due to their optimal balance of effectiveness and tolerability. Brexpiprazole and quetiapine showed no significant efficacy over placebo in response rates. Esketamine and psilocybin exhibited lower tolerability. The findings advocate for ECT, ketamine, esketamine, and psilocybin as preferred treatments, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes.
Esketamine and ketamine are perioperative analgesics and anesthetics widely used in Europe and the United States, but their application in China is still in early stages. They primarily act through non-competitive antagonism of the N-methyl-D-aspartate receptor (NMDAR), though they also affect multiple other receptors and pathways. Due to potential side effects and addictive properties, they are subject to regulatory controls. This review synthesizes recent research on their classical applications—analgesia, sedation, and anesthesia—as well as emerging antidepressant, anti-tumor, and anti-inflammatory effects. By integrating preclinical and clinical findings and considering limitations, the review aims to inform clinical use and future research directions for these versatile agents.