Evidence map›Paper›PMID 41607072›Full record

SynthesisEuropean psychiatry : the journal of the Association of European Psychiatrists2026

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 and 2 more

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European psychiatry : the journal of the Association of European Psychiatrists, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Andy LuDepartment of Psychology, University of Western Ontario, London, ON, Canada.ORCID 0009-0004-4475-2658
Heidi XuBrain and Cognition Discovery Foundation, Toronto, ON, Canada.ORCID 0009-0007-9048-3630
Gia Han LeBrain and Cognition Discovery Foundation, Toronto, ON, Canada.ORCID 0000-0001-6457-0086
Christine E DriBrain and Cognition Discovery Foundation, Toronto, ON, Canada.
Sabrina WongBrain and Cognition Discovery Foundation, Toronto, ON, Canada.ORCID 0009-0002-0928-3433
Roger HoDepartment of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Bing CaoKey Laboratory of Cognition and Personality, Faculty of Psychology, Ministry of Education, Southwest University, Chongqing, 400715, P. R. China.ORCID 0000-0001-5963-2676
Heidi Ka Ying LoDepartment of Psychiatry, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong.ORCID 0000-0003-2551-5230
Taeho Greg RheeDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0003-4961-3361
Liyang YinBrain and Cognition Discovery Foundation, Toronto, ON, Canada.
Hernan F Guillen-BurgosPontificia Universidad Javeriana, Department of Psychiatry and Mental Health, Bogota DC, Colombia.ORCID 0000-0003-1835-431X
Roger S McIntyreDepartment of Psychiatry, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-4733-2523

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKetamine 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

methodsWe 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.

results16 studies were identified: 12 clinical (

conclusionsThe 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.

Indexed as

Antidepressive AgentsDepressive Disorder, Treatment-ResistantKetamineReceptors, OpioidAnimalsHumansNarcotic AntagonistsAntidepressive AgentsEsketamineKetamineNarcotic AntagonistsReceptors, Opioiddepressive disorderesketamineketaminemajoropioidreceptorstreatment-resistant

Identifiers

PMID41607072
PMCPMC12925689

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.