SUBSTANCE ABUSE: ADDICTION & RECOVERY
Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence
The COMBINE Study and Its Implications
By Raymond F. Anton, MD |
June 8, 2011
Dr Anton is Distinguished University Professor, Professor of Psychiatry and Behavioral Sciences, and Director of the Center for Drug and Alcohol Programs as well as the Clinical Neurobiology Laboratory at the Medical University of South Carolina in Charleston. He reports that in the past year, he has been a consultant for GlaxoSmithKline, Alkermes, and Eli Lilly. He has received grant support from Eli Lilly, Johnson & Johnson, Alkermes, Schering, Lundbeck, GlaxoSmithKline, and Abbott Labs.
What is the take-home message for clinicians? The COMBINE study and many other clinical trials have shown that there are many people living and working in communities across the United States who are willing to volunteer for alcohol(Drug information on alcohol)-dependence treatment trials. Many of these individuals have never before received treatment and many have not been asked by, or have not been honest with, their primary care providers and/or psychiatrists about the extent of their alcohol use. Specifically, however, the COMBINE study showed that health care providers can either treat alcohol-dependent individuals with naltrexone(Drug information on naltrexone) and medical management or refer them to a trained counselor who might use the types of techniques prescribed in the CBI manual.7
There are several caveats. Medical management consisted of seeing the patient 9 times over 4 months (initially once a week and then every 2 to 4 weeks). Each 15- to 20-minute session emphasized medication adherence and provided support, education, and laboratory monitoring (eg, feedback about biomarkers of drinking). There is no evidence that providing medical management less frequently, or for less time, would be as effective. However, this might be individualized depending on the severity of alcohol addiction, the degree of medication adherence, and the patient’s response.
Those who received CBI alone (or by extension, other moderately intensive weekly counseling sesions) did not fare as well. While we cannot say for sure whether just seeing a health care provider without taking a pill would be enough to enhance the counseling treatment, the suspicion would be that the more skilled support provided to the patient, the better the expected outcome.
While the evidence for the differential response to naltrexone based on genotype is very promising and important, it is still too early to prescribe this approach given the relatively limited post hoc information that is available. Prospective studies currently under way should provide more definitive information.
The COMBINE study was only one trial designed by academics to maximize internal scientific validity; results cannot be extrapolated to all populations and individuals. For instance, it excluded individuals with other significant psychiatric and medical illnesses (more often the rule than the exception in some clinical settings)—individuals deemed too severely ill or who needed hospitalization. In addition, not all communities have trained addiction professionals or medication prescribers to deliver the types of treatments offered in the COMBINE study.
The options for treating individuals with alcohol use disorders is expanding. We can hope that advances in addiction neuroscience will pave the way for new and improved treatments.
Also in this Special Report
1. Anton RF, O’Malley SS, Ciraulo DA, et al; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295:2003-2017.
2. Matching alcoholism treatments to client heterogeneity: Project MATCH posttreatment drinking outcomes. J Stud Alcohol. 1997;58:7-29.
3. Berglund M, Thelander S, Salaspuro M, et al. Treatment of alcohol abuse: an evidence-based review. Alcohol Clin Exp Res. 2003;27:1645-1656.
4. Mann K, Lehert P, Morgan MY. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis. Alcohol Clin Exp Res. 2004;28:51-63.
5. Mason BJ, Goodman AM, Chabac S, Lehert P. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J Psychiatr Res. 2006;40:383-393.
6. Pettinati HM, Weiss RD, Dundon W, et al. A structured approach to medical management: a psychosocial intervention to support pharmacotherapy in the treatment of alcohol dependence. J Stud Alcohol Suppl. 2005;15:170-178.
7. National Institute on Alcohol Abuse and Alcoholism. COMBINE Monograph Series. http://pubs.niaaa.nih.gov/publications/COMBINE.htm. Accessed March 16, 2011.
8. Miller WR, ed. Combined Behavioral Intervention Manual: A Clinical Research Guide for Therapists Treating People With Alcohol Abuse and Dependence. Vol 1. Bethesda, MD: US Dept of Health and Human Services; 2004. NIH publication 04-5288.
9. Zarkin GA, Bray JW, Aldridge A, et al; COMBINE Cost-Effectiveness Research Group. Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients. Arch Gen Psychiatry. 2008;
10. Zarkin GA, Bray JW, Aldridge A, et al. The effect of alcohol treatment on social costs of alcohol dependence: results from the COMBINE study. Med Care. 2010;48:396-401.
11. Oslin DW, Berrettini W, Kranzler HR, et al. A functional polymorphism on the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology. 2003;28:1546-1552.
12. Anton RF, Oroszi G, O’Malley S, et al. An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008;65:135-144.
13. Weiss RD, O’Malley SS, Hosking JD, et al; COMBINE Study Research Group. Do patients with alcohol dependence respond to placebo? Results from the COMBINE Study. J Stud Alcohol Drugs. 2008;69:878-884.
14. Johnson BA, Rosenthal N, Capece JA, et al; Topiramate for Alcoholism Advisory Board; Topiramate for Alcoholism Study Group. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA. 2007;298:1641-1651.
Information for professionals about self-help for patients and for the identification and treatment (including medications) of individuals with alcohol use disorders:
• Anton RF. Naltrexone for the management of alcohol dependence. N Engl J Med. 2008;359:715-721.
• National Institute on Alcohol Abuse and Alcoholism. http://www.niaaa.nih.gov/Pages/default.aspx. Accessed March 16, 2011.
For more on the COMBINE study:
• Collaborative Studies Coordination Center. COMBINE Study. http://www.cscc.unc.edu/COMBINE/publications. Accessed March 16, 2011.