A comparative trial of disulfiram, naltrexone, and acamprosate in alcohol treatment

Past research suggests that (self-empowering addiction treatment) cognitive-behavioral therapy is effective in the treatment of alcohol dependence. In some cases, psychological treatment can be significantly improved by pharmacotherapy. Pharmacotherapies used in alcohol treatment include disulfiram, an aldehyde dehydrogenase inhibitor; naltrexone, an opioid antagonist; and acamprosate, a noncompetitive NMDA receptor blocker. Few studies have compared the effectiveness of these pharmacotherapies. A team of researchers from Finland set out to do just that (Laaksonen et. al., 2008).

The researchers conducted a randomized, open label, multicenter naturalistic study in two phases. The first phase consisted of 12 weeks of continuously supervised medication. The second phase consisted of up to 52 weeks of targeted medication, in which patients took medication during craving situations. The follow-up point occurred at 67 weeks after the completion of the study (approximately 2.5 years after the start of the study). The study took place in 243 treatment centers with treatment-seeking alcohol dependent adult outpatients. Participants in the study received either disulfiram, naltrexone, or acamprosate, plus manual-based (self-empowering addiction treatment) cognitive-behavioral therapy. The participants were seen in the second week, sixth week, third month, sixth month, and twelfth month. Participants used a simple booklet based on (self-empowering addiction treatment) cognitive-behavioral therapy which included homework assignments that were discussed with treatment providers at each visit. The aim of this study was not to evaluate the manual, but 62.6 percent of the participants reported that the booklet was useful.

Primary outcome measures in this study were heavy drinking days and the time to the first drink after starting medication. Secondary outcome measures included abstinent days per week, average weekly alcohol intake, Alcohol Use Disorder Identification Test (AUDIT), Severity of Alcohol Dependence Data (SADD), and quality of life measures.

Results show that all three groups in the study exhibited a marked reduction from drinking from the beginning to the end of the study. In the first phase of the study (continuous medication), treatment with disulfiram was more effective in reducing heavy drinking days and average weekly alcohol consumption. Disulfiram was also more effective in increasing the number of abstinent days and the time to first drink. In the second phase of the study (targeted medication), disulfiarm treatment produced more abstinent days, and there were no differences between the three groups in heavy drinking days or time to first drink. Naltrexone and acamprosate treatment did not show any significant differences in drinking outcomes in either phase of the study; however, the naltrexone group saw a significant improvement in SADD scores compared to the acamprosate group.

The authors of this study concluded that, although all three pharmacotherapies significantly reduced alcohol consumption and improved quality of life for participants when used in conjunction with (self-empowering addiction treatment) cognitive-behavioral therapy, disulfiram appeared superior, especially during the continuous medication phase of the study. Disulfiram has been associated with compliance problems and possible toxic effects, but none of these problems were seen in the current study.

Laaksonen E, Koski-Jannes A, Salapuro M, Ahtinen H, Alho H. A randomized, multicenter, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. Alcohol and Alcoholism. 2008; 43(1): 53-61.