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Evidenced based dual diagnosis treatment with focus on the underlying causation is generally recognized as the modality best capable of achieving the highest outcome measurements of success. All of the providers listed in our directory use the same protocols in an effort to maximize the efficacy of the treatment services provided.

In the construct of the many individual alcohol and opioid treatment services offered by our providers, the use of the COMBINE Study methodology is the primary foundation from which each of the protocols were developed.

Study Defines Most Effective Alcoholism Treatments
Naltrexone, Counseling and Medical Management
By Buddy T, About.com Guide

A three-year study of 1,383 of alcohol dependent patients in treatment has shown that the medication naltrexone and up to 20 sessions of alcohol counseling by a behavioral specialist are equally effective treatments for alcohol dependence when combined with structured outpatient medical management. Surprisingly the “Combining Medications and Behavioral Interventions for Alcoholism,” or COMBINE Study as it is known, also found that adding acamprosate (Campral) to the treatment program did not improve treatment outcomes.

The study, published in the Journal of the American Medical Association, showed that patients that received naltrexone, specialized alcohol counseling, or both had the best drinking outcomes after 16 weeks of outpatient treatment. All of the patients in the study also received Medical Management — an intervention consisting of nine brief, structured outpatient sessions provided by a health care professional.

“These results demonstrate that either naltrexone or specialized alcohol counseling — with structured medical management — is an effective option for treating alcohol dependence,” said Mark L. Willenbring, M.D., Director, Division of Treatment and Recovery Research, NIAAA. “Although medical management is somewhat more intensive than the alcohol dependence interventions offered 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.

“Medical management’s application in primary care and general mental health care settings would expand access to effective treatment dramatically, while offering patients greater choice.”

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) launched COMBINE in 2001 to identify the most effective current treatments and treatment combinations for alcohol dependence. It is the largest clinical trial ever conducted of pharmacologic and behavioral treatments for alcohol dependence. The COMBINE study was conducted at 11 academic sites that recruited and randomly assigned 1,383 recently abstinent, alcohol-dependent patients to one of nine treatment groups.

According to a NIAAA news release, “eight treatment groups received medical management; four of these received naltrexone (100 milligrams a day), acamprosate (3 grams a day), both naltrexone and acamprosate, or placebo pills. The other four groups received in addition received specialized alcohol counseling.

Combined Behavioral Intervention

“Called Combined Behavioral Intervention (CBI), the counseling integrated cognitive-behavioral therapy, motivational enhancement, and techniques to enhance mutual help group participation — all treatments shown in earlier studies to be beneficial. Patients assigned to the specialized alcohol counseling could receive up to twenty 50-minute sessions in addition to medical management; the median number received was 10 sessions.
“To test for any effects of pill taking (placebo), the researchers assigned some patients to a ninth group that received specialized alcohol counseling, but no pills, and no more than four visits with a health professional for general medical advice.”

COMBINE Study Highlights

Here are the highlights of the COMBINE study results after 16 weeks:
All groups substantially reduced drinking during treatment. Overall percent days abstinent tripled, from 25 to 73 percent, and alcohol consumption per week decreased from 66 to 13 drinks, a decrease of 80 percent. Patients who received medical management plus either naltrexone or specialized counseling showed similarly improved outcomes (PDA= 80.6 percent and 79.2 percent, respectively), compared with patients who received medical management and placebo pills (75.1 percent).

Patients who received naltrexone reported less craving for alcohol. The odds of a good composite clinical outcome relative to patients who received medical management and placebo were 1.82 for patients who received medical management plus Combined Behavioral Intervention (but no naltrexone), 1.92 for patients who received medical management, Combined Behavioral Intervention, and naltrexone, and 2.16 for patients who received medical management and naltrexone (but no Combined Behavioral Intervention). That is, adding either naltrexone or specialized alcohol counseling to medical management almost doubled the chance to do well.

Part Two: Findings After One Year

After patients participated in the 16-week treatment program, the “Combining Medications and Behavioral Interventions for Alcoholism,” study reported the following findings for the patients one year later: Naltrexone continued to show a small advantage of less relapse to heavy drinking, most markedly in patients who received medical management only but not in those who received specialized alcohol counseling.

Although a return to at least one heavy drinking day was common during the 1-year follow-up period, overall abstinence was still significantly improved after 1 year (59 to 68 percent PDA) compared with study entry (25 percent PDA). Good composite clinical outcomes at 1 year were observed in 38 to 50 percent of patients, with the worst outcomes in patients who received medical management plus placebo and better outcomes in those who received medical management plus either naltrexone or specialized alcohol counseling.

“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.” Contrary to expectation, the study found that 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, according to a news release.

Acamprosate No Better Than Placebo

Also contrary to expectation, the medication acamprosate was shown similar to placebo in this trial. “Previous studies have shown that acamprosate alone and in combination with naltrexone can work in settings that reflect clinical practice,” Mason said. “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.”

Acamprosate Findings ‘Perplexing’

In an accompanying editorial in the JAMA publication, Henry R. Kranzler, M.D., of the University of Connecticut School of Medicine, Farmington, commented on the findings of the COMBINE Study: “While this important study provides evidence of the efficacy of some treatments for alcohol dependence, it also raises a number of questions. In view of studies from Europe providing consistent evidence that acamprosate helps to maintain abstinence, the lack of efficacy of this medication in the COMBINE Study is perplexing.

“Although population differences must be considered, differences in study design may have contributed to the lack of replication of the European acamprosate studies. The modest effects of the specific treatments and a lack of additive or synergistic benefits of combining treatments suggest that other compounds and therapeutic approaches should be explored to yield further improvements in the treatment of alcohol dependence.”

Widely Available Treatment

“The findings from the COMBINE Study should be of great interest to primary care physicians treating patients with alcohol dependence. Patients who decline an offer of pharmacological treatment to reduce their drinking can be referred for intensive behavioral treatment. “Notably, however, the beneficial effects of naltrexone were seen in the context of medical management similar to what is routinely available in primary care practice. This offers the prospect that an efficacious treatment for alcohol dependence can be made as widely available as are current treatments for smoking cessation and major depression.”

COMBINE Study reports in JAMA

The medication naltrexone and up to 20 sessions of alcohol counseling by a behavioral specialist are equally effective treatments for alcohol dependence when delivered with structured medical management, according to results from “Combining Medications and Behavioral Interventions for Alcoholism” (The COMBINE Study). Results from the National Institutes of Health-supported study show that patients who received naltrexone, specialized alcohol counseling, or both demonstrated the best drinking outcomes after 16 weeks of outpatient treatment. All patients also received Medical Management (MM), an intervention consisting of nine brief, structured outpatient sessions provided by a health care professional. Contrary to expectations, the researchers found no effect on drinking of the medication acamprosate and no additive benefit from adding acamprosate to naltrexone. Effect of Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence appears in the current issue of the Journal of the American Medical Association, Volume 295, Number 17, pages 2003-2017.

NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA) launched COMBINE in 2001 to identify the most effective current treatments and treatment combinations for alcohol dependence. The largest clinical trial ever conducted of pharmacologic and behavioral treatments for alcohol dependence, COMBINE was carried out at 11 academic sites that recruited and randomly assigned 1383 recently abstinent, alcohol-dependent patients to one of nine treatment groups.

Eight treatment groups received MM; four of these received naltrexone (100 milligrams a day), acamprosate (3 grams a day), both naltrexone and acamprosate, or placebo pills. The other four groups received in addition received specialized alcohol counseling. Termed Combined Behavioral Intervention (CBI), the counseling integrated cognitive-behavioral therapy, motivational enhancement, and techniques to enhance mutual help group participation–all treatments shown in earlier studies to be beneficial. Patients assigned to the specialized alcohol counseling could receive up to twenty 50-minute sessions in addition to medical management; the median number received was 10 sessions. To test for any effects of pill taking (placebo), the researchers assigned some patients to a ninth group that received specialized alcohol counseling, but no pills, and no more than four visits with a health professional for general medical advice.

During the 16 weeks of treatment and 1 year after the treatment, the researchers assessed the patients for the percentage of days abstinent from alcohol and time to the first heavy drinking day, defined as 4 or more drinks per day for women and 5 or more drinks per day for men. They also assessed the odds of good clinical outcome, defined as abstinence or moderate drinking without alcohol-related problems. As in other large clinical trials, the researchers found that most patients showed substantial improvement during treatment and that both the overall level of improvement and the differences between treatment groups diminished during the follow-up period. In the COMBINE study, however, naltrexone continued to show a small advantage for preventing relapse at 1 year after the end of active treatment.

“These results demonstrate that either naltrexone or specialized alcohol counseling–with structured medical management–is an effective option for treating alcohol dependence,” said Mark L. Willenbring, M.D., Director, Division of Treatment and Recovery Research, NIAAA. “Although MM is somewhat more intensive than the alcohol dependence interventions offered 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. MM’s application in primary care and general mental health care settings would expand access to effective treatment dramatically, while offering patients greater choice.” To expand its application, NIAAA will develop an abbreviated version of MM to be available in early summer. Print copies of the treatment manuals used in COMBINE are available by order from http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials.

The COMBINE results provide guidance for applying today’s treatment tools. NIAAA continues to explore new treatment tools in more than 50 current medication trials, in studies to better understand the mechanisms of action in behavioral treatments, and in our search for new molecular targets and novel compounds for clinical testing,” according to Raye Z. Litten, Ph.D., COMBINE’s government director and co-leader of NIAAA medications development team.

COMBINE chairpersons Raymond F. Anton, M.D., Department of Psychiatry, Medical University of South Carolina, and Stephanie O’Malley, Ph.D., Yale University School of Medicine, and Drs. Willenbring and Litten will discuss the COMBINE results in a news teleconference, to be held May 1, 2006, from 1:00 to 2:00 PM. To request the call-in code, please telephone Ann Bradley (301/443-3860 or 301/443-0595) before 12:00 PM on May 1; to join the call, please telephone 1-877-807-5706 between 12:50 and 1:00 PM.

For interviews with Drs. Anton and O’Malley, telephone 301/443-3860 through May 2. For interviews with the COMBINE study authors, please see author list that follows. For interviews with Drs. Willenbring and Litten, please telephone the NIAAA Press Office, 301/443-3860.

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at www.niaaa.nih.gov.

The National Institutes of Health (NIH) – The Nation’s Medical Research Agency – includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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COMBINE Study Authors Raymond F. Anton, M.D., Chair (2000-2006). Medical University of South Carolina, 843-792-2626; Stephanie S. O’Malley, Ph.D., Chair (1997-1999), Yale University School of Medicine 203-500-5889

Domenic A. Ciraulo, M.D. Boston University School of Medicine 617-638-8491
Ron A. Cisler, Ph.D. University of Wisconsin-Milwaukee 414-699-8554

David Couper, Ph.D., University of North Carolina 919-962-3229
Dennis M. Donovan, Ph.D. University of Washington 206-543-0937/206-616-3192
James D. Hosking, Ph.D. University of North Carolina 919-962-3085
Bankole A. Johnson, M.D., Ph.D. University of Virginia Health System
University of Texas Health Science Center 434-924-9241

Joseph LoCastro, Ph.D. Veterans Affairs Boston Health Care System/
Boston University School of Medicine 617-278-4488

Richard Longabaugh, Ed.D., Roger Williams Medical Center/Brown University 401-465-4116

Barbara J. Mason, Ph.D., University of Miami School of Medicine
The Scripps Research Institute 858-504-0905
Margaret E. Mattson, Ph.D., Staff Collaborator, NIAAA, 301-443-0638
William R. Miller, Ph.D.
University of New Mexico 505-277-1821/508-710-3633
Helen M. Pettinati, Ph.D., University of Pennsylvania 215-547-0311
Carrie L. Randall, Ph.D., Medical University of North Carolina
Robert Swift, M.D. Roger Williams Medical Center/Brown University 401-965-1708

Roger D. Weiss, M.D.
Harvard University/McLean Hospital 617-855-2110

Lauren D. Williams, M.D., University of Miami School of Medicine c/o 858-504-0905

Allen Zweben, D.S.W., Columbia University School of Social Work
University of Wisconsin-Milwaukee/Columbia 212-851-2887

COMBINE FINDINGS: HIGHLIGHTS

At 16 weeks—All groups substantially reduced drinking during treatment. Overall percent days abstinent tripled, from 25 to 73 percent, and alcohol consumption per week decreased from 66 to 13 drinks, a decrease of 80 percent. Patients who received medical management plus either naltrexone or specialized counseling showed similarly improved outcomes (PDA= 80.6 percent and 79.2 percent, respectively), compared with patients who received medical management and placebo pills (PDA=75.1 percent). Patients who received naltrexone reported less craving for alcohol.

The odds of a good composite clinical outcome relative to patients who received medical management and placebo were 1.82 for patients who received MM plus CBI (but no naltrexone), 1.92 for patients who received MM, CBI, and naltrexone, and 2.16 for patients who received MM and naltrexone (but no CBI). That is, adding either naltrexone or specialized alcohol counseling to medical management almost doubled the chance to do well. About 6 to 7 patients need to be treated with medical management and either specialized alcohol counseling or naltrexone for one additional patient to have a good clinical outcome. This “number needed to treat” is similar to that for other chronic conditions such as depression, Crohn disease, or type 2 diabetes.

At 16 weeks + 1 year—Naltrexone continued to show a small advantage of less relapse to heavy drinking, most markedly in patients who received medical management only but not in those who received specialized alcohol counseling.

Study Results Offer Guidance in Treatment

While many treatment approaches were found helpful, the authors report that the patients who were most successful in abstaining from alcohol 16 weeks after treatment were those prescribed naltrexone under medical management and those participating in a multi-session program of alcohol counseling delivered by a behavioral specialist. 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.

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.

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