About 8 million individuals in the U.S. currently meet diagnostic criteria for alcohol dependence (also called alcoholism), a leading preventable cause of illness and death and a major contributor to health care costs, according to background information in the article. In primary care settings, the prevalence of alcohol use disorders ranges from 20 percent to 36 percent; most of those patients are never treated and, if they are, do not receive specialty care. Several behavioral treatments and at least two medications approved by the U.S. FDA, naltrexone and acamprosate, have shown efficacy in the treatment of alcohol dependence. However, no large-scale randomized controlled study has evaluated whether combined drug treatment with or without behavioral therapy could improve outcome.
Raymond F. Anton, M.D., of the Medical University of South Carolina, Charleston, and colleagues evaluated the effectiveness in treating alcohol dependence with medical management and naltrexone, acamprosate, or both, with or without combined behavioral intervention (CBI) provided by behavioral health specialists. The trial (the COMBINE Study), conducted from January 2001 – January 2004, included 1,383 recently alcohol-abstinent volunteers with a diagnosis of primary alcohol dependence. The participants were divided into 9 groups. Eight groups of patients received medical management with 16 weeks of naltrexone or acamprosate, both, and/or both placebos, with or without CBI. Medical management included sessions with a medical professional focused on enhancing medication adherence and alcohol abstinence. A ninth group received CBI only (no pills). Patients were evaluated for up to one year after treatment.
The researchers found that all groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management, CBI plus medical management and placebos, or both naltrexone and CBI plus medical management had higher percentages of days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only. Naltrexone also reduced the risk of a heavy drinking day over time, most evident in those receiving medical management but not CBI.
Acamprosate showed no significant effect on drinking compared with placebo, either by itself or with any combination of naltrexone, CBI, or both. During the 16 weeks of treatment, there was an overall difference in percent days abstinent between those receiving placebo pills and medical management alone (73.8), placebo pills and medical management plus CBI (79.8), and CBI alone (no pills or medical management) (66.6). One year after treatment, these between-group effects were similar but no longer significant.
"In conclusion, within the context of medical management, naltrexone yielded outcomes similar to those obtained from specialist behavioral treatment (i.e., CBI). We found no evidence of efficacy for acamprosate and also no evidence of incremental efficacy for combinations of naltrexone, acamprosate, and CBI. Somewhat unexpectedly, we observed a positive effect of receiving placebo medication and medical management over and above that seen with specialist-delivered behavioral therapy alone. Medical management of alcohol dependence with naltrexone appears to be feasible and, if implemented in primary, and other, health care settings, could greatly extend patient access to effective treatment. Future studies that evaluate the usefulness of continued or intermittent care of alcohol-dependent individuals over the longer term should be considered," the authors write.
(JAMA. 2006;295:2003-2017. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This study was supported by National Institute on Alcohol Abuse and Alcoholism Cooperative Agreements and career scientist awards. The acamprosate, naltrexone, and their matching placebos used in this study were donated by Lipha Pharmaceuticals. For financial disclosure information, please see the JAMA article.
Editorial: Evidence-Based Treatments for Alcohol Dependence – New Results and New Questions
In an accompanying editorial, Henry R. Kranzler, M.D., of the University of Connecticut School of Medicine, Farmington, comments on the findings of the COMBINE Study.
"While this important study provides evidence of the efficacy of some treatments for alcohol dependence, it also raises a number of questions. In view of studies from Europe providing consistent evidence that acamprosate helps to maintain abstinence, the lack of efficacy of this medication in the COMBINE Study is perplexing. Although population differences must be considered, differences in study design may have contributed to the lack of replication of the European acamprosate studies. The modest effects of the specific treatments and a lack of additive or synergistic benefits of combining treatments suggest that other compounds and therapeutic approaches should be explored to yield further improvements in the treatment of alcohol dependence."
"The findings from the COMBINE Study should be of great interest to primary care physicians treating patients with alcohol dependence. Patients who decline an offer of pharmacological treatment to reduce their drinking can be referred for intensive behavioral treatment. Notably, however, the beneficial effects of naltrexone were seen in the context of medical management similar to what is routinely available in primary care practice. This offers the prospect that an efficacious treatment for alcohol dependence can be made as widely available as are current treatments for smoking cessation and major depression," Dr. Kranzler writes.
(JAMA. 2006;295:2075-2076. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Dr. Kranzler receives support from the National Institute on Alcohol Abuse and Alcoholism. He reported receiving research support from and serving as a consultant or speaker for Alkermes, Bristol-Myers Squibb, Drug Abuse Sciences, Forest Laboratories, and Ortho-McNeil Pharmaceuticals.
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