Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

26. Psychopharmacological Treatments 595onset (but not late-onset) alcoholics, and reduced drinking in these individuals(Johnson et al., 2000), but these results need to be replicated in larger controlledtrials.Not yet available in the United States, acamprosate (calcium acetylhomotaurinate),an analogue of homocysteic acid, has a structure similar togamma-aminobutyric acid (GABA) and, as such, has been reported to stimulateinhibitory GABA transmission and to antagonize excitatory amino acids(Zeise, Kasparov, Capogna, & Zieglgansberger, 1993). These properties havebeen postulated to be important to reduction in alcohol craving (Littleton,1995). Acamprosate has no abuse potential, hypnotic muscle relaxant, oranxiolytic properties. Furthermore, it is not hepatically metabolized and is,instead, excreted as unchanged drug by the kidneys, allowing its safe use inthose with liver impairment, although it should not be administered to thosewith renal insufficiency (Wilde & Wagstaff, 1997). A review of acamprosatestudies showed that in 14 of 16 controlled clinical trials, those treated withacamprosate had higher rates of treatment completion for alcohol dependence,longer abstinence period to first drink, and higher overall abstinence rates thanthose treated with placebo (Mason, 2001; Mason & Ownby, 2000). Acamprosatetreatment in several studies also was associated with decreases in laboratoryindices of alcohol consumption, including gamma-glutamyltransferase andcarbohydrate-deficient transferrin (Graham, Wodak, & Whelan, 2002). Thedrug was found to be well tolerated and acceptable to patients.Several studies have compared naltrexone and acamprosate treatment foralcohol dependence. In a 1-year follow-up study, no differences were observedin time to first drink, but time to first relapse was shorter in acamprosate-treatedpatients, while those treated with naltrexone were found to have a greatercumulative number of days of abstinence, to consume fewer drinks at one time,and to have less craving for alcohol (Rubio, Jimenez-Arriero, Ponce, & Palomo,2001). In a study comparing naltrexone, acamprosate, naltrexone and acamprosatein combination, and placebo, both active drugs and the combination wereassociated with significantly longer time to first drink and relapse to alcohol userelative to placebo. Additionally, there was a trend toward more positive outcomesin the naltrexone-treated group relative to the acamprosate-treatedgroup. The combination was more effective than placebo or acamprosate butnot naltrexone (Kiefer et al., 2003).BENZODIAZEPINE PHARMACOTHERAPIESThe benzodiazepines are some of the most frequently prescribed medications inthe United States due to their efficacy as anxiolytics and muscle relaxants,rapid onset of action, and relatively low risk of toxicity relative to other medicationswith similar indications. However, benzodiazepines, similar to alcohol,