{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T15:02:08Z","timestamp":1768489328253,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H01015"],"award-info":[{"award-number":["20H01015"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04302"],"award-info":[{"award-number":["22H04302"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23H05286"],"award-info":[{"award-number":["23H05286"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The concomitant use of lamotrigine and valproic acid, a uridine diphosphate (UDP)\u2010glucuronosyltransferase inhibitor, is a known risk factor for lamotrigine\u2010induced rashes, which may develop into fatal or severe cutaneous adverse reactions. No drugs other than valproic acid have been shown to increase lamotrigine concentrations in humans by inhibiting UDP\u2010glucuronosyltransferase. The treatment of bipolar disorder and epilepsy is often combined with other medications, which may affect the risk of rash. We aimed to identify medications that increased the risk of lamotrigine\u2010induced rashes using clinical data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used VigiBase to search for drugs associated with the increased number of reported severe cutaneous adverse reactions when combined with lamotrigine. In a retrospective study, we collected information on patients from electronic medical records and used propensity score matching to compare the incidence of lamotrigine\u2010induced rash with and without flunitrazepam use. Furthermore, we compared lamotrigine concentrations between patients treated with and without flunitrazepam in a prospective observational study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>VigiBase analysis showed that flunitrazepam significantly increased the reporting odds ratio for lamotrigine\u2010related severe cutaneous adverse reactions. In the retrospective study, combining lamotrigine with flunitrazepam significantly increased the incidence of rashes. In the prospective observational study, lamotrigine with flunitrazepam significantly increased the concentration\u2010to\u2010dose ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Flunitrazepam use may affect lamotrigine concentration and increase the risk of rash. These results have implications for the choice of sleep medication. In addition, when lamotrigine is used in combination with flunitrazepam, the lamotrigine dosing design should address lamotrigine\u2010induced rash management.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pcn.13866","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T11:04:47Z","timestamp":1752750287000},"page":"629-635","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Flunitrazepam increases the risk of lamotrigine\u2010induced cutaneous adverse reactions: Combined analysis of medical big data and clinical research"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1847-3754","authenticated-orcid":false,"given":"Hiroshi","family":"Bando","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical Sciences Tokushima University  Tokushima Japan"},{"name":"Department of Pharmacy Tokushima 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