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Metabolic processes influencing treatment response are not captured by blood monitoring. This study evaluates whether exhaled breath metabolomic profiles reflect treatment response and adverse effects in adults receiving antiseizure therapy, using epilepsy as a model for pharmacodynamic phenotyping.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A single\u2010center observational cohort of 117 adults provided 127 breath samples during stable antiseizure treatment. Exhaled breath samples were analyzed using secondary electrospray ionization high\u2010resolution mass spectrometry. Machine\u2010learning models with nested cross\u2010validation were used to classify treatment response and adverse effects, and pathway\u2010level analyses were performed to provide biological context. Findings were compared with an independent, predominantly pediatric cohort analyzed using the same workflow.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Breath metabolomic profiles distinguished responders from nonresponders and individuals with and without adverse effects, whereas serum drug concentrations showed no meaningful association. Classification models achieved areas under the curve of 0.84 for treatment response and 0.88 for adverse effects, with good calibration. Pathway\u2010level alterations were directionally consistent across cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Breath metabolomics supports a non\u2010invasive approach to pharmacodynamic phenotyping that captures treatment\u2010related metabolic states not reflected by serum drug concentrations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71169","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:37:57Z","timestamp":1790606277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breath Signatures of Antiseizure Medication Response and Tolerability in Adults With Epilepsy"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5238-372X","authenticated-orcid":false,"given":"Kai","family":"Fricke","sequence":"first","affiliation":[{"name":"Department of Pulmonology University Hospital Zurich  Zurich Switzerland"},{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1486-3603","authenticated-orcid":false,"given":"Diego Manuel","family":"Baur","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital Zurich  Zurich Switzerland"},{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-0708","authenticated-orcid":false,"given":"Kapil Dev","family":"Singh","sequence":"additional","affiliation":[{"name":"University Children's Hospital Basel  Basel 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