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Baclofen, a GABA<jats:sub>B<\/jats:sub>agonist, has been identified as a potential pharmacotherapy for AUD. In a 16-week double-blind, randomized, placebo-controlled trial, we investigated 30 and 90\u2009mg\/day of baclofen compared to placebo and examined effects of dose, sex, and level of pretreatment drinking. One hundred and twenty participants with DSM-IV alcohol dependence (age 46.1 (sd\u2009=\u200910.1) years, 51.7% male) were randomized after exclusion for unstable medical\/psychiatric illness and\/or dependence on drugs other than nicotine. Seventy-three participants completed the trial. A main effect of baclofen was found [%HDD (F(2,112)\u2009=\u20094.16,<jats:italic>p<\/jats:italic>\u2009=\u20090.018,<jats:italic>d<\/jats:italic>\u2009=\u20090.51 95%CI (0.06\u20130.95), 13.6 fewer HDD) and %ABST (F(2,112)\u2009=\u20093.68,<jats:italic>p<\/jats:italic>\u2009=\u20090.028,<jats:italic>d<\/jats:italic>\u2009=\u20090.49 95%CI (0.04\u20130.93), 12.9 more abstinent days)] and was driven by the 90\u2009mg\/day dose. A sex\u2009\u00d7\u2009dose interaction effect was present for both %HDD (F(2,110)\u2009=\u20095.48,<jats:italic>p<\/jats:italic>\u2009=\u20090.005) and %ABST (F(2,110)\u2009=\u20093.19,<jats:italic>p<\/jats:italic>\u2009=\u20090.045). Men showed a marginally positive effect for 90\u2009mg\/day compared to PBO (%HDD t(110)\u2009=\u20091.88,<jats:italic>p<\/jats:italic>\u2009=\u20090.063,<jats:italic>d<\/jats:italic>\u2009=\u20090.36 95%CI (\u22120.09\u20130.80), 15.8 fewer HDD days; %ABST t(110)\u2009=\u20091.68 (<jats:italic>p<\/jats:italic>\u2009=\u20090.096,<jats:italic>d<\/jats:italic>\u2009=\u20090.32 95%CI (\u22120.12\u20130.76), 15.7 more ABST)) with no effect for 30\u2009mg\/day. Women showed a positive effect for 30\u2009mg\/day (%HDD, t(110)\u2009=\u20093.19,<jats:italic>p<\/jats:italic>\u2009=\u20090.002,<jats:italic>d<\/jats:italic>\u2009=\u20090.61 95%CI (0.16\u20131.05), 26.3 fewer HDD days; %ABST t(110)\u2009=\u20092.73,<jats:italic>p<\/jats:italic>\u2009=\u20090.007,<jats:italic>d<\/jats:italic>\u2009=\u20090.52 95%CI (0.07\u20130.96), 25.4 more ABST days) with marginal effects for 90\u2009mg\/day on %ABST (<jats:italic>p<\/jats:italic>\u2009=\u20090.06) with drop-outs\/dose reduction from sedative side-effects of 59% in women at 90\u2009mg\/day compared to 5% for men. These findings support the hypothesis that baclofen has efficacy in AUD and suggest that dose and sex be further explored as potential moderators of baclofen response and tolerability.<\/jats:p>","DOI":"10.1038\/s41386-021-01055-w","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T16:04:08Z","timestamp":1624291448000},"page":"2250-2256","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Efficacy and tolerability of baclofen in a U.S. community population with alcohol use disorder: a dose-response, randomized, controlled trial"],"prefix":"10.1038","volume":"46","author":[{"given":"James C.","family":"Garbutt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei B.","family":"Kampov-Polevoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cort","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Stansbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9617-095X","authenticated-orcid":false,"given":"Laura","family":"Willing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Gallop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"1055_CR1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1001\/jamapsychiatry.2015.0584","volume":"72","author":"BF Grant","year":"2015","unstructured":"Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, et al. 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