Largest Clinical Trial in History finds Naltrexone and Therapy Effective for Alcoholi

[Don S]

-- University of Wisconson Milwaukee Press Release --

Results Appear in May Issue of JAMA

Milwaukee only Midwestern site for clinical trials

MILWAUKEE – Results for the COMBINE Study, a six-year, multi-site, collaborative project funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), appear in the current (May) issue of the Journal of the American Medical Association JAMA.

The University of Wisconsin–Milwaukee’s Center for Addiction and Behavioral Health Research (CABHR), in partnership with Aurora Health Care, administered the Milwaukee study at Aurora Sinai Medical Center, the only Midwestern site for COMBINE. Milwaukee is a preferred site for clinical trials concerning alcohol abuse and dependence because the region has a large population of heavy drinkers, according to the NIAAA.

Encouraged by the results of earlier studies involving the use of medications to treat alcoholism, NIAAA launched COMBINE in 2001 to identify the most effective current treatments and treatment combinations for alcohol dependence. COMBINE also tested the efficacy of two “anti-craving drugs” – naltrexone and acamprosate – to determine whether treatment success rates improved when the drugs were combined with each other or with certain “talk” therapies.

The largest clinical trial ever conducted of pharmacologic and behavioral treatments for alcohol dependence, COMBINE also was conducted at 10 other study sites, including Yale, Brown, Boston, and Harvard universities. The academic sites recruited and randomly assigned 1,383 recently abstinent alcohol-dependent patients to one of nine treatment groups.

Findings released in the JAMA article conclude that:

Health care professionals can successfully treat alcohol dependence. Medical management by a doctor, nurse, or other health professional, combined with either the medication naltrexone or specialized alcohol counseling, produced the best outcomes after 16 weeks of active treatment and one year later. However, combining all three treatments (medical management, naltrexone, and specialized counseling) did not add benefit compared to medical management with either naltrexone or counseling alone.

Most patients had good outcomes. After 16 weeks of treatment, compared to study entry, percentage of days abstinent nearly tripled, from 25 percent to 73 percent, and weekly drinking dropped 80 percent. After one year, about one-half of patients had good overall clinical outcomes.

Acamprosate, found effective in previous studies, was not effective in COMBINE, and naltrexone did not work better when combined with acamprosate.

Allen Zweben, director of CABHR when the study was initiated, is principal investigator of the Milwaukee aspect study. Zweben is now associate dean for research and sponsored projects at Columbia University. The COMBINE study was transferred to Columbia University’s School of Social Work in 2005, when Zweben moved there. Columbia University has a subcontract with UWM, however; all the subjects were seen and follow-up data were gathered in Milwaukee. Ron Cisler, senior scientist at CABHR, is a site co-principal investigator for COMBINE. Cisler also is an associate professor in the UWM College of Health Sciences, and director of the Center for Urban Population Health in Milwaukee. Lance Longo, M.D., of Aurora Health Care’s Sinai Medical Center and Aurora Psychiatric Hospital, is medical director for the Milwaukee site.

“Our data from the COMBINE study underscore the importance of having treatment options for alcohol patients, including naltrexone or specialized alcohol counseling with medical management,” said Zweben. “The findings are particularly relevant to psychologists, social workers and other behavioral specialists, many of whom see large numbers of individuals with alcohol problems in various settings. An important next step would be to develop an alcohol education curriculum that would incorporate the findings from the COMBINE study.”

“Families and prospective patients can be assured by these results that medical management, when combined with either naltrexone or specialized alcohol counseling, are effective options for treating alcohol dependence,” said Mark L. Willenbring, M.D., director, Division of Treatment and Recovery Research, NIAAA. “Currently, about nine in 10 patients with alcohol dependence do not receive professional treatment. Medical management is a strategy that could potentially be implemented in a variety of health care settings, such as primary care and general mental health care. This would expand access to effective treatment dramatically.”

Study authors were surprised that acamprosate, shown in many earlier studies to be effective, demonstrated no effect in COMBINE. COMBINE recruited patients from the community, whereas most earlier studies of acamprosate were in patients from clinical, often inpatient, settings – usually a source of more severe cases. “Ongoing analyses of the COMBINE data, including in-progress pharmacogenetic studies, will address why our patients responded or failed to respond to a medication,” said COMBINE chairperson Raymond F. Anton, M.D., Department of Psychiatry, Medical University of South Carolina.

COMBINE and other future research advances call for a new paradigm that integrates alcohol dependence treatment into mainstream medical care, Dr. Willenbring says. “Although the medical management intervention used in COMBINE is more intensive than that provided in most of today’s health care settings, it is not unlike other patient care models such as initiating insulin therapy in patients with diabetes mellitus.”

Since 1991, CABHR at UWM has been active in conducting and disseminating research related to drug and alcohol problems, as well as a host of other behavioral concerns. CABHR scientists work in close collaborative partnerships with other institutions and community-based agencies. The center has a long record of federal, state, local and foundation funding for its many research and training projects.

Many health and mental health organizations are involved as CABHR partners. Michael Fendrich has served as director of CABHR since September. CABHR is housed in the Helen Bader School of Social Welfare at UWM.

For more information on CABHR, consult the Web site: www.uwm.edu/Dept/CABHR/