{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T02:12:52Z","timestamp":1770689572185,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>The cytochrome P450 2D6 (CYP2D6) metabolizes around 20% of currently prescribed medications, including the antipsychotic risperidone. Previous studies reported greater odds of switching antipsychotic medication from risperidone among CYP2D6 poor metabolizers (PM) without considering treatment duration up to the switch. Risperidone treatment failure, defined as risperidone treatment duration up to switching medication, was analyzed among 515 patients of the PsyMetab cohort using Kaplan\u2013Meier estimates with log\u2010rank tests and Cox multivariate regression. Risperidone\u2010to\u2010paliperidone ratios were higher among CYP2D6 PMs (median: 2.78) vs. the other phenotypes (median: 0.14, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). After 1\u2009year of treatment, the proportion of patients who switched from risperidone was 44%. This proportion was increased to 70% among PMs, vs. 42% among the other CYP2D6 phenotypes (<jats:italic>P<\/jats:italic>\u2009=\u20090.026). PMs' risk of switching increased over time (interaction PM*treatment duration: 1.01; <jats:italic>P<\/jats:italic>\u2009=\u20090.011), becoming statistically significant after 3\u2009months of treatment, with 1.79 (<jats:italic>P<\/jats:italic>\u2009=\u20090.028), 3.7 times (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and 16.3 times higher (<jats:italic>P<\/jats:italic>\u2009=\u20090.001) risk of switch at 3, 6, and 12\u2009months, respectively (95% confidence intervals: 1.07\u20133.01, 1.91\u20137.17, and 3.13\u201385.37, respectively). Considering a pharmacogenetic\u2010guided treatment, the number of patients needed to genotype to find one PM and lower the switching proportion from 70% to 42% would be 65. In conclusion, CYP2D6 PM status presented an increased risk of switching from risperidone over 1\u2009year of treatment, the risk increasing over time and becoming statistically significant after the first 3\u2009months of treatment.<\/jats:p>","DOI":"10.1002\/cpt.3691","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T01:45:01Z","timestamp":1747014301000},"page":"263-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cytochrome P450 2D6 Poor Metabolizers and Risperidone Treatment Failure: A 1\u2010Year Longitudinal Study"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5579-0199","authenticated-orcid":false,"given":"Marianna","family":"Piras","sequence":"first","affiliation":[{"name":"Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry Lausanne University Hospital, 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