Alcohol impacts multiple neurochemical receptors in the central nervous system. Several pharmacologic agents have been developed for the prevention and reduction of cravings of alcoholism based on these distinct receptor mechanisms. Two medications that have been used in the treatment of alcoholism are naltrexone and acamprosate. These agents have different mechanisms that influence various neuroreceptors, which attenuate the psychoactive effects of alcohol and reduce cravings for this substance. Both medications have proved effective in reducing the likelihood of relapse in alcoholism. It is uncertain if either medication is more efficacious or if combining the two medications potentiates their efficacy. Kiefer and associates studied the efficacy of naltrexone and acamprosate in the prevention of alcohol relapse and compared these with a placebo. They also compared the combination of these medications to see if this would be more effective than use of single agents or placebo.
The trial was a randomized, double-blinded, placebo-controlled study. Participants were enrolled if they had been admitted to an inpatient alcohol withdrawal unit and went through detoxification. They were randomly assigned to receive naltrexone, acamprosate, naltrexone plus acamprosate, or placebo for 12 weeks. There were 40 subjects in each of the four groups. The dosages for naltrexone (50 mg per day) and acamprosate (1,998 mg per day) remained stable throughout the study. Patients were assessed initially and then weekly during the trial. The assessment consisted of an interview, completion of a self-reporting questionnaire, and laboratory screening. Primary outcome measures included time to first drink, time to relapse, and the accumulative abstinence time.
There were no significant differences between the four treatment groups with regard to sociodemographic characteristics and alcohol-related data. Most (118) of the subjects were men. Naltrexone, acamprosate, and the combination of the two were significantly more effective than placebo when comparing the primary outcomes. Both medications independently and in combination were more effective in reducing the likelihood of relapse for the “first” drink (see accompanying figure). The combination was more effective in improving the relapse time to the first drink than acamprosate alone. Baseline craving scores were significantly higher than scores during treatment, regardless of treatment modality. Both agents were tolerated well, and no serious adverse drug reactions were reported. None of the active treatment groups had any laboratory abnormalities noted except in those participants who relapsed.
The authors conclude that naltrexone and acamprosate alone are effective agents as abstinence therapies in alcoholism. The combination of these two medications can enhance effectiveness and does not increase patients' risks for developing adverse drug reactions.