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, Hernán F Guillen-Burgos, Roger S McIntyre
European Psychiatry 2026 DOI: 10.1192/j.eurpsy.2026.10157 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Citations | 4 |
| Key findings | 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.