The COMBINE Study shows that medical management with naltrexone or with specialized behavioral therapy can be effective treatments for alcohol dependence, according to an article in the May 3 issue of the Journal of the American Medical Association.

Several behavioral treatments and at least two medications approved by the U.S. Food and Drug Administration, naltrexone and acamprosate, have shown efficacy in 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, MD, 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 provided by behavioral health specialists.

The trial (the COMBINE Study), conducted from January 2001 to January 2004, included 1,383 recently alcohol-abstinent volunteers with a diagnosis of primary alcohol dependence. The participants were divided into nine groups. Eight groups received medical management with 16 weeks of naltrexone, acamprosate, both, and/or both placebos, with or without behavioral intervention.

Medical management included sessions with a medical professional focused on enhancing medication adherence and alcohol abstinence. A ninth group received combined behavioral intervention only (no medication). 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, combined behavioral intervention plus medical management and placebos, or both naltrexone and behavioral intervention plus medical management had higher percentages of days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 percent of people who received 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 behavioral intervention.

Acamprosate showed no significant effect on drinking compared with placebo, either by itself or with any combination of naltrexone, behavioral intervention, 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 behavioral intervention (79.8), and behavioral intervention 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 wrote.