Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?
Andy Lu, Heidi Xu, Gia Han Le, Christine E. Dri, Sabrina Wong, Roger Ho, Bing Cao, Heidi Ka Ying Lo, Taeho Greg Rhee, Liyang Yin, Hernan F. Guillen-Burgos, Roger S. McIntyre
European Psychiatry January 1, 2026 DOI: 10.1192/j.eurpsy.2026.10157 via OpenAlex
Summary
AI-generated from the abstractKetamine's antidepressant effects in treatment-resistant depression may be partially mediated by the opioid system, but the evidence is mixed. Because opioid receptor antagonists inconsistently reduce these effects, the opioid system likely acts as a context-dependent modulator rather than a primary mediator, especially at standard antidepressant doses.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Citations | 4 |
| Key finding | The opioid system likely functions as a context-dependent modulator of ketamine's antidepressant effects rather than a primary mediator. |
Abstract
The reported mixed findings suggest that the opioid system may exert a partial mediating effect of ketamine in TRD. However, given the inconsistent attenuation of ketamine's antidepressant effects by opioid receptor antagonists, the opioid system likely functions as a context-dependent modulator rather than a primary mediator, particularly at standard antidepressant doses.