Effects and mechanisms of esketamine on depression by targeting gut microbiota: A narrative review

Esketamine, a rapid-acting antidepressant approved by the FDA and EMA in 2019 and 2020, may work partly by modulating the gut microbiota and its metabolites. This review summarizes current research on esketamine's antidepressant effects and discusses the pharmacological mechanism involving gut microbiota regulation, a pathway also implicated in fecal microbiota transplantation's ability to alleviate depression.

Study at a glance

Abstract

Depression is a severe and recurrent neuropsychiatric disease with high prevalence, disability, and mortality, which imposes a heavy burden on national public health and the economy. Traditional antidepressants demonstrate delayed effects, low cure rates, and inadequate therapeutic effectiveness for managing treatment-resistant depression. Numerous studies have proved that esketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, can produce a rapid and sustained antidepressant effect, which was approved by the FDA and EMA in 2019 and 2020, respectively. However, the pharmacological mechanism underlying the antidepressant effects of esketamine remains inadequately understood. Previous studies have shown that gut microbiota plays a significant role in central nervous system regulation such as emotional behavior and cognitive function. Moreover, fecal microbiota transplantation can alleviate depression by regulating the disorder of gut microbiota. Notably, esketamine exhibited a therapeutic effect against depression by modulating the gut microbiota and its metabolites. Therefore, this review summarized the current research progress on the functional role and mechanism of esketamine in the treatment of depression, as well as discussed the pharmacological mechanism for esketamine’s antidepressant effects by regulating gut microbiota.