Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?

ABSTRACT:

Background

Ketamine and esketamine produce rapid and sustained antidepressant effects in persons with treatment-resistant depression (TRD). Although it is posited that these effects are largely attributed to N-methyl-D-aspartate receptor antagonism, the potential involvement of the opioid system remains unclear. This systematic review investigates whether ketamine and esketamine antidepressant efficacy is mediated through the opioid system.

Methods

We conducted a systematic search of preclinical and clinical studies investigating the potential involvement of the opioid system in the antidepressant effects of ketamine and esketamine. Database searches on PubMed, Cochrane Library, Embase and PsycINFO occurred from inception to September 27, 2025.

Results

16 studi

SUBMITTER: Lu A 

PROVIDER: S-EPMC12925689 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature