Addiction Exchange
News from the worlds of research and clinical practice
Volume 3, No. 7: NIAAA's COMBINE Study
May 1, 2001

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Welcome to Addiction Exchange, a forum for the exchange of clinical practice and research information among clinicians, scientists, educators, and administrators in the field of addiction.
     In this issue, we discuss the National Institute on Alcohol Abuse and Alcoholism (NIAAA) multisite COMBINE study (Combining Medications and Behavioral Interventions), a clinical trial researching treatments for alcohol dependence. COMBINE is the first national study on alcoholism treatment to evaluate the effectiveness of behavioral treatments alone and in combination with medications.

        Alcohol dependence “is characterized by an abnormal appetite for alcohol that leads to significant impairment  tolerance, impaired control over intake, physical dependence and, often, severe craving following sustained abstinence,” according to NIAAA Director Enoch Gordis, M.D. More than 8 million adults in the U.S. meet the clinical criteria for alcoholism. As many as half of them relapse at least once, and only a minority achieve long-term remission of the disease. Another six million meet the diagnostic criteria for alcohol abuse disorder, which involves harmful drinking that continues despite life-affecting problems but does not entail physiological addiction.
        The COMBINE study will take place over the next 24 months at 11 treatment research centers: the Universities of Washington, Texas, Miami, New Mexico, Pennsylvania, and Wisconsin-Milwaukee; the Medical University of South Carolina; and Boston, Yale, Brown and Harvard universities. The University of North Carolina is the site for the Coordinating Center.
        The study, which will recruit 1,375 people with alcohol dependence, will provide participants with one or both of two behavioral treatments (moderate intensity and lower intensity) and one or both of two medications (naltrexone and acamprosate) or a placebo. Study subjects will attend outpatient sessions for four months, then return for three followup visits over the following 12 months. All interventions will include a component supporting compliance to medications and a reduction in drinking.
        The moderate-intensity behavioral treatment includes motivational enhancement therapy, cognitive-behavioral skills training and patient involvement in groups such as Alcoholics Anonymous  treatments shown in NIAAA’s Project MATCH to increase abstinent days and reduce heavy drinking. (Motivational enhancement therapy, based on motivational psychology, is designed to help patients mobilize personal resources to effect change. Cognitive-behavioral therapy is based on social learning theory and is designed to provide skills for avoiding relapse.) The lower-intensity behavioral treatment is intended to support sobriety and enhance medication compliance; it is also designed to be incorporated into the daily routine of health care practitioners.
        The FDA-approved drug naltrexone (Revia), an opioid blocker, interferes with brain neurotransmitter systems that produce the rewarding effects of alcohol. Researchers have shown that patients treated with this drug are less likely to relapse to heavy drinking. Acamprosate (Campral), used in Europe and currently under review by the FDA, is believed to normalize abnormalities in the neurotransmitter systems involved in alcohol withdrawal. It may also ease the discomfort of abstinence, thus helping to prevent drinking. One of the questions the study will explore is whether treatment effectiveness is improved by pairing a medication that reduces the risk of any drinking with one that reduces the risk of heavy drinking.
        “COMBINE is based on the accumulated knowledge of two decades in which NIAAA researchers have applied rigorous clinical trial methodology to test treatments for alcoholism,” said Richard K. Fuller, M.D., director of NIAAA’s Division of Clinical and Prevention Research. In 1996, Project MATCH, another multisite national trial, demonstrated the effectiveness of involvement in such groups as AA and of the two behavioral treatments being used in the COMBINE clinical trial. (See 1996 Project MATCH news release at http://silk.nih.gov/silk/niaaa1/releases/match.htm on NIAAA’s website.) In addition, neuroscientists have advanced the understanding of the biology of drinking behavior over the past 10 years. From among the most promising pharmacologic and behavioral treatments, COMBINE will attempt to determine the best treatment combinations.
        Alcoholism results from a combination of drinker characteristics, including intrinsic neurochemical factors (some of which may be genetic) and environmental risk factors. Brain imaging studies have shown that both medications and behavioral treatments can influence brain function and resulting behaviors. It is hoped that this study will show that the behavioral and pharmacological treatments tested will complement, perhaps even enhance, each other.
     NIAAA, an institute of the National Institutes of Health, conducts over 90 percent of alcohol research in the U.S. for research on the causes, consequences, prevention and treatment of alcoholism and alcohol-related problems. For additional information about alcohol research, visit NIAAA’s website at http://www.niaaa.nih.gov.

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Mid-Atlantic Addiction Technology Transfer Center
Funded by Center for Substance Abuse Treatment of
Substance Abuse and Mental Health Services Administration
mid-attc@mindspring.com
http://www.mid-attc.org
804-828-9910