{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:17Z","timestamp":1790621897204,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S\u2010ketamine, used as a tool compound for rapid\u2010acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomized, double\u2010blind, double\u2010dummy, placebo\u2010controlled, 4\u2010way crossover study in 16 healthy participants, we administered S\u2010ketamine in a therapeutic intravenous dose (IV), a low and high oral dose, versus placebo. Measurements were conducted from baseline up to 7\u2009days post\u2010dose using Transcranial Magnetic Stimulation combined with electromyography (TMS\u2010EMG) and encephalography (TMS\u2010EEG), pharmaco\u2010electroencephalography (pEEG), alongside drug and metabolite plasma concentrations. Outcomes were analysed using mixed\u2010effects ANCOVA and cluster\u2010based permutation testing. Post\u2010hoc concentration\u2013effect relationships were explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IV S\u2010ketamine induced an acute reduction in motor\u2010evoked potential (MEP) amplitude and sustained attenuation of long\u2010interval intracortical inhibition (LICI\n                      <jats:sub>50<\/jats:sub>\n                      ), the latter showing a linear concentration\u2013effect relationship with the parent compound. Acute TEP modulation was observed across all treatments, whereas delayed effects occurred only after IV and high\u2010dose oral. pEEG showed acute reductions in alpha, beta and delta power (eyes closed) and sustained increases in delta power (eyes open) following IV and high\u2010dose oral S\u2010ketamine; with delta power exhibiting a less analyte\u2010specific linear concentration\u2013effect relationship.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We provide evidence suggestive of delayed pharmacodynamic effects of S\u2010ketamine in healthy participants sustained up to 7\u2009days post\u2010dose, using TMS and pEEG derived measures, which are markedly distinct from its acute effects and may be relevant to understand its antidepressant efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70649","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:45:52Z","timestamp":1782308752000},"page":"3534-3545","source":"Crossref","is-referenced-by-count":0,"title":["Sustained pharmacodynamic effects of S\u2010ketamine on cortical excitability and resting\u2010state brain activity: A randomized, placebo\u2010controlled trial"],"prefix":"10.1002","volume":"92","author":[{"given":"Catherine M. 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