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March 3, 2026European Psychiatry4 citationsOpen Access

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

ĀA. Imamog ̄luHXHaoping XuGLGia Han Le

Key Points

  • Ketamine's antidepressant efficacy is influenced by the opioid system's partial mediation — especially in treatment-resistant depression.
  • Findings show that opioid receptor antagonists inconsistently affect ketamine's antidepressant effects across varied contexts.
  • The analysis examines the role of opioid mechanisms in a context-dependent manner; clinical implications remain unclear.
  • Context-dependent modulation of ketamine suggests a complex interaction, needing further exploration on efficacy and dosage.

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.

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Cite This Study

̄lu et al. (2026) studied this question.

synapsesocial.com/papers/69a75d07c6e9836116a266f9https://doi.org/10.1192/j.eurpsy.2026.10157
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