Evidence map›Paper›PMID 42340194›Full record

Trial reportBritish journal of clinical pharmacology2026

Sustained pharmacodynamic effects of S-ketamine on cortical excitability and resting-state brain activity: A randomized, placebo-controlled trial.

Catherine M K E de Cuba, Annika A de Goede, Joost C van Mechelen, Laura G J M Borghans, Liam van der Aa, Erik Olofsen, Maria J Juachon, Robert J Doll, Amy Gillespie, Catherine J Harmer and 2 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 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. Trial
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.

Catherine M K E de CubaCentre for Human Drug Research, Leiden, The Netherlands.
Annika A de GoedeCentre for Human Drug Research, Leiden, The Netherlands.
Joost C van MechelenCentre for Human Drug Research, Leiden, The Netherlands.
Laura G J M BorghansCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0001-5580-1153
Liam van der AaCentre for Human Drug Research, Leiden, The Netherlands.
Erik OlofsenCentre for Human Drug Research, Leiden, The Netherlands.
Maria J JuachonCentre for Human Drug Research, Leiden, The Netherlands.
Robert J DollCentre for Human Drug Research, Leiden, The Netherlands.
Amy GillespieDepartment of Psychiatry, University of Oxford, Oxford, UK.
Catherine J HarmerDepartment of Psychiatry, University of Oxford, Oxford, UK.
Gabriël E JacobsCentre for Human Drug Research, Leiden, The Netherlands.
Jules A A C HeubergerCentre for Human Drug Research, Leiden, The Netherlands.ORCID https://orcid.org/0000-0001-7202-5088

Funding

Centre for Human Drug Research
6 · The paper itself

Abstract

aimsThis study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S-ketamine, used as a tool compound for rapid-acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects.

methodsIn this randomized, double-blind, double-dummy, placebo-controlled, 4-way crossover study in 16 healthy participants, we administered S-ketamine in a therapeutic intravenous dose (IV), a low and high oral dose, versus placebo. Measurements were conducted from baseline up to 7 days post-dose using Transcranial Magnetic Stimulation combined with electromyography (TMS-EMG) and encephalography (TMS-EEG), pharmaco-electroencephalography (pEEG), alongside drug and metabolite plasma concentrations. Outcomes were analysed using mixed-effects ANCOVA and cluster-based permutation testing. Post-hoc concentration-effect relationships were explored.

resultsIV S-ketamine induced an acute reduction in motor-evoked potential (MEP) amplitude and sustained attenuation of long-interval intracortical inhibition (LICI

conclusionWe provide evidence suggestive of delayed pharmacodynamic effects of S-ketamine in healthy participants sustained up to 7 days post-dose, using TMS and pEEG derived measures, which are markedly distinct from its acute effects and may be relevant to understand its antidepressant efficacy.

Indexed as

Antidepressive AgentsBrainCortical ExcitabilityKetamineAdministration, OralAdultCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodElectroencephalographyElectromyographyEvoked Potentials, MotorFemaleHumansMaleTranscranial Magnetic StimulationAntidepressive AgentsKetaminepharmaco‐electroencephalographyS‐ketaminetranscranial magnetic stimulation

Identifiers

PMID42340194
PMCPMC13619092

What OpenQuestion holds

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Registered trials

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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.