Most Effective Alcoholism Treatments Defined

Naltrexone, Counseling and Medical Management

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Multiple Treatment Approaches Work. © Getty Images

The massive COMBINE study published in 2006 followed 1,383 patients over a three-year period to determine what combination of treatment, medication and counseling was the most effective for treating alcohol abuse disorders.

The "Combining Medications and Behavioral Interventions for Alcohol Dependence" study produced some surprising results when it revealed that the newest medication approved for the treatment of alcoholism failed to improve treatment outcomes.

The study did find that when combined with a structured outpatient medical management intervention consisting of nine brief sessions conducted by a healthcare professional that the medication naltrexone and up to 20 session of alcohol conseling were equally effective treatments for alcoholism.

Surprisingly, the study found that combining acamprosate (Campral) with the medical management program did not improve outcomes.

"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," Willenbring said.

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 (PDA) 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.

Follow-Up 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.

Medication Gave Patients an Advantage

"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."

Surprisingly, 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."

Naltrexone Could Become 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."

The COMBINE study was the largest clinical trial ever of pharmacologic and behavrioral treatments for alcoholism, involving 11 academic sites and 1,383 patients divided into nine different treatment groups.

Anton, RF, et al. "Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence. The COMBINE Study: A Randomized Controlled Trial." Journal of the American Medical Association May 2006

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