However, some patients may receive optimal benefit from 125 to 500 mg/day.6 Additional unpleasant symptoms such as chest

pain, seizures, hepatotoxicity, renal failure, and even death have been reported in severe cases.6,62 Controlled trials of disulfiram versus placebo have not demonstrated buy Y-27632 significant improvement over placebo,63,64 and metaanalyses have only shown slight improvement in drinking.65 A large Veterans Cooperative Study with over 600 subjects found, however, that disulfiram may be effective Inhibitors,research,lifescience,medical in patients with no major comorbid psychiatric disorder and who were motivated for abstinence.64 More recently, an evaluation of subjects with current depression on disulfiram reported lower craving over time than subjects with depression on naltrexone.66 The utility of combining disulfiram with other therapeutic interventions has also been examined. In a trial of disulfiram and acamprosate, the number of abstinent days was greater when utilizing a combination of disulfiram and acamprosate than using Inhibitors,research,lifescience,medical either medication alone.67 Naltrexone acts as an antagonist at the Inhibitors,research,lifescience,medical opioid receptors, which are known to mediate the rewarding effects of alcohol and thus thought to reduce desire or craving of alcohol. Studies have found that naltrexone is more effective than placebo in promoting abstinence, reducing heavy drinking days and decreasing relapse rates,6,68-70 particularly

when it is combined with cognitive behavioral therapy71-73 Naltrexone has also shown greater efficacy when compared with acamprosate. In a randomized controlled trial comparing the efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, significant increases in time to first relapse was seen in those receiving naltrexone in Inhibitors,research,lifescience,medical subjects with no depression and low dependency.74 Furthermore, combined pharmacotherapy studies have also demonstrated Inhibitors,research,lifescience,medical that naltrexone

administered with behavioral therapy can significantly reduce the risk of heavy drinking.75 Naltrexone is prescribed as 50 mg oral administration, most commonly for 12 weeks, and can also be given as a long-acting depot formulation every 4 weeks. Acamprosate attenuates alcohol desire or craving by normalizing the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutaminergic excitation that occurs in alcohol withdrawal and early abstinence. Acamprosate, Dichloromethane dehalogenase when given at 2 g administered three times daily, has increased abstinence by 50% in over 3000 patients across a dozen clinical trials.76-78 Side effects such as diarrhea are generally well tolerated. A placebo-controlled trial enrolled 272 patients and treated patients for 48 weeks. Compared with placebo, acamprosate-treated alcoholdependent patients had twice the rate of sustained abstinence at 48 weeks (43% vs 21%), and this difference from placebo was sustained at 96 weeks after starting the medication (37% vs 17 %).