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This effect on NMDA glutamatergic transmission may play a role against the increased glutamatergic transmission determined by alcohol withdrawal. To investigate the efficacy and safety of OXC in relapse prevention we compared OXC at different dosages with Naltrexone (NAL) in a 90 days randomised open\u2010label trial. Craving and psychiatric symptoms improvements were the secondary endpoints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighty\u2010four detoxified alcohol dependent subjects currently meeting clinical criteria for alcohol dependence were randomised into three groups: 27 patients received 50\u2009mg of naltrexone, 29 received 1500\u20131800\u2009mg of oxcarbazepine (OXC high), 28 patients 600\u2013900\u2009mg of oxcarbazepine (OXC low). Craving (VAS; OCDS) and withdrawal (AWRS) rating scales were applied; psychiatric symptoms were evaluated through the SCL\u201090\u2010R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significantly larger number of subjects remained alcohol free in the OXC high group (58.6%) with respect to both the OXC low (42.8%) and the NAL groups (40.7%). Comparing the OCDS total scores at the end of the treatment, the improvement was significantly greater for the NAL group with respect to the OXC low group. The reduction of the Hostility\u2010Aggression subscore of the SCL\u201090\u2010R was significantly greater in the OXC high group than that of the other groups. Dual diagnosis patients had a better outcome when treated with OXC high.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>OXC at a dosage of 1500\u20131800\u2009mg\/day might be beneficial in terms of alcohol relapse prevention. The low dosage formulation did not show the same trend, but it still remain in the same range as NAL. The mechanism involved in the efficacy of oxcarbazepine in relapse prevention could be less related to craving and more connected to the treatment of the comorbid psychiatric symptomatology and the alcohol protracted withdrawal syndrome. 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