{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T19:22:40Z","timestamp":1762111360073,"version":"3.41.2"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["P60 AA03510","R01 AA023192","R01 AA025539"],"award-info":[{"award-number":["P60 AA03510","R01 AA023192","R01 AA025539"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Topiramate reduces drinking and alcohol\u2010related problems and is increasingly being used to treat alcohol use disorder (AUD). In a randomized controlled trial (RCT) of topiramate, rs2832407, a single nucleotide polymorphism (SNP) in the <jats:italic>GRIK1<\/jats:italic> gene moderated topiramate's effects (Study 1). However, a second RCT (Study 2) did not replicate the SNP's moderating effect during treatment. The current analysis combines data from these two studies to examine topiramate's effects on alcohol\u2010related outcomes and on its pharmacogenetic moderation during a 6\u2010month post\u2010treatment period. This analysis includes 308 individuals with problematic alcohol use (67% male; mean age\u2009=\u200951.1; topiramate: 49%, placebo: 51%). It uses generalized linear mixed models to examine changes in self\u2010reported alcohol consumption and alcohol\u2010related problems and concentrations of the liver enzyme \u03b3\u2010glutamyltransferase. The report combines published 3\u2010 and 6\u2010month follow\u2010up data from Study 1 with similar, unpublished data from Study 2. Despite robust effects of topiramate on drinking during treatment, the overall multivariate medication effects on outcomes during 3\u2010 and 6\u2010month follow\u2010up were not significant (<jats:italic>p<\/jats:italic>\u2009=\u20090.08 and <jats:italic>p<\/jats:italic>\u2009=\u20090.26, respectively). The moderating effect of the SNP on primary treatment outcomes was also not significant during either follow\u2010up period (<jats:italic>p<\/jats:italic>\u2009=\u20090.13 and <jats:italic>p<\/jats:italic>\u2009=\u20090.16, respectively). However, during the 3\u2010month post\u2010treatment period, drinks per day was significantly lower in the topiramate group than the placebo group in the rs2832407*CC\u2010genotype group. The robust effects of topiramate on alcohol\u2010related outcomes during treatment diminish substantially once the medication is discontinued. Research is needed both to determine the optimal treatment duration and to identify clinically useful pharmacogenetic moderators of topiramate for treating AUD.<\/jats:p>","DOI":"10.1111\/adb.13130","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T05:15:04Z","timestamp":1643174104000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Post\u2010treatment effects of topiramate on alcohol\u2010related outcomes: A combined analysis of two placebo\u2010controlled trials"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0450","authenticated-orcid":false,"given":"Henry R.","family":"Kranzler","sequence":"first","affiliation":[{"name":"Department of Psychiatry Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"VISN4 MIRECC Philadelphia VAMC  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Feinn","sequence":"additional","affiliation":[{"name":"Frank Netter School of Medicine Quinnipiac University  Hamden Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Pond","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5137-9714","authenticated-orcid":false,"given":"Emily","family":"Hartwell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"VISN4 MIRECC Philadelphia VAMC  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-1859","authenticated-orcid":false,"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine and VA CT Healthcare Center  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard C.","family":"Crist","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Witkiewitz","sequence":"additional","affiliation":[{"name":"Department of Psychology (KW), Center on Alcohol, Substance Use, and Addictions University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Janssen Pharmaceuticals.Topamax prescribing information.https:\/\/www.janssenlabels.com\/package-insert\/product-monograph\/prescribing-information\/TOPAMAX-pi.pdf. 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