The paper appears in the May 2 issue of the Journal of the American Medical Association and reports on the largest clinical trial ever conducted of pharmacologic and behavioral treatments for alcohol dependence.
"The most robust finding in the study is that those receiving any medication did much better than those who received no pills at all," says The Scripps Research Institute's Professor Barbara Mason, an author of the paper. "This should be a wakeup call. With less than one percent of those seeking help for alcohol dependence receiving a prescription, medication is underutilized. Medication for alcoholism can offer patients an advantage for their recovery, especially in a real-world setting."
Another important aspect of the study, says Mason, is that it offers new safety data on the prescription drugs used in the trial, naltrexone and acamprosate, which were administered at higher-than-standard doses. "We had no serious drug-related events during the course of the research," she says. "That fact should offer prescribing physicians a high degree of comfort."
About eight million individuals in the United States currently meet the diagnostic criteria for alcohol dependence, also called alcoholism, a leading preventable cause of morbidity and mortality and a major contributor to health care costs, according to the paper's background information. In primary care settings, the prevalence of alcohol use disorders ranges from 20 percent to 36 percent.
While several behavioral treatment programs and drugs now approved by the U.S. Food and Drug Administration had been shown effective for treating alcohol dependence in previous studies, no large-scale randomized controlled study had evaluated whether combined drug treatment with or without behavioral therapy could improve outcome. In 2001, the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, launched "Combining Medications and Behavioral Interventions for Alcoholism" (COMBINE) to identify the most effective current treatments and treatment combinations.
The trial, conducted at 11 sites around the country from January 2001 to January 2004, recruited and randomly assigned 1,383 recently abstinent alcohol dependent patients.
Individuals were assigned to one of nine treatment groups. In eight of the nine groups, patients received what the paper called "medical management," attending sessions with a physician, nurse, physicians assistant, or pharmacist where these health care professionals reviewed the diagnosis, recommended abstinence and mutual-help participation, and reviewed patients' progress. Some groups also received pills: naltrexone (100 milligrams a day), acamprosate (3 grams a day), both naltrexone and acamprosate, or placebos. Four groups also received "Combined Behavioral Intervention (CBI)"-an alcohol counseling program with a behavioral specialist that was offered in up to 20 50-minute sessions. A ninth group received the specialized counseling, but no pills.
Patients were assessed during the 16 weeks of active treatment and one year after treatment.
Contrary to expectation, neither combining naltrexone with the medication acamprosate nor combining naltrexone with the program's specialized behavioral treatment provided an additive benefit to taking naltrexone alone.
Also contrary to expectation, the medication acamprosate was shown similar to placebo in this trial. Mason comments, "Previous studies have shown that acamprosate alone and in combination with naltrexone can work in settings that reflect clinical practice. The COMBINE trial involved a 4.5-hour intake session and follow-up sessions of up to two hours, as well as contact with up to five specialized staff persons at every visit. This may have increased placebo response such that differences between drugs were very small, even with naltrexone, so I would interpret these outcomes with caution for use in a real-world setting."
Mason-who is co-director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research, director of Scripps Research's Division of Psychopharmacology of the Molecular and Integrative Neurosciences Department, and adjunct faculty at University of Miami School of Medicine and Rockefeller University-is currently conducting ancillary studies to the COMBINE trial at Scripps Research.
Mason's laboratory explores the physiological changes in the brain that drive excessive drinking and create vulnerability to relapse. She also investigates the viability of using new compounds to modulate the neurological effects of alcohol, reduce excessive intake, and prevent relapse. Those interested in participating in one of her clinical trial studies at the Scripps Research La Jolla campus should call (858) 784-7867.
The COMBINE paper, titled "Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence," appears in the May 2 issue of the Journal of the American Medical Association (285: 2075-2076). In addition to Mason, the study's authors are: Raymond F. Anton, Stephanie S. O'Malley, Domenic A. Ciraulo, Ron A. Cisler, David Couper, Dennis M. Donovan, James D. Hosking, Bankole A. Johnson, Joseph LoCastro, Richard Longabaugh, Margaret E. Mattson, William R. Miller, Helen M. Pettinati, Carrie L. Randall, Robert Swift, Roger D. Weiss, Lauren D. Williams, and Allen Zweben.
About The Scripps Research Institute
The Scripps Research Institute, headquartered in La Jolla, California, in 18 buildings on 40 acres overlooking the Pacific Ocean, is one of the world's largest independent, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel.
Scripps Florida, a 364,000 square-foot, state-of-the-art biomedical research facility, will be built in Palm Beach County. The facility will focus on basic biomedical science, drug discovery, and technology development. Palm Beach County and the State of Florida have provided start-up economic packages for development, building, staffing, and equipping the campus. Scripps Florida now operates with approximately 160 scientists, technicians, and administrative staff at 40,000 square-foot lab facilities on the Florida Atlantic University campus in Jupiter.
Journal
JAMA