Clinical Question: What interventions are most effective in the treatment of alcohol dependence?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Behavioral interventions and at least two medications—naltrexone (Revia) and acamprosate (Campral)—are effective in the treatment of alcohol dependence. Whether combining pharmacotherapy with behavior therapy will improve outcomes is unknown. These investigators randomized (concealed allocation) 1,383 adults (428 women and 955 men; median age = 44 years) meeting. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. criteria for alcohol dependence to one of nine groups for 16 weeks of outpatient treatment.

Eight of the groups received medical management, a nine-session intervention lasting 20 to 45 minutes that focused on medication compliance and abstinence. Four of these groups also received combined behavioral intervention consisting of up to 20 counseling sessions lasting 50 minutes given by alcohol treatment subspecialists. Patients in all eight groups received naltrexone, acamprosate, placebo, or acamprosate plus naltrexone. Naltrexone was given once per day, beginning with 25 mg and titrated to 100 mg, as tolerated. Acamprosate 1,000 mg was administered three times per day. The ninth group received combined behavioral intervention without medications or medical management. All participants underwent assessment regularly for up to one year after enrollment. Those assessing outcomes remained blinded to medication group assignment. Follow-up occurred for 94 percent of patients at 16 weeks and for 82 percent at one year. Serum transferrin protein levels (percent carbohydrate-deficient transferrin) served as a check for self-reported drinking. All analyses were by intention to treat.

During treatment, patients receiving naltrexone plus medical management, combined behavioral intervention plus medical management, or both naltrexone and combined behavioral intervention plus medical management had a significantly higher percentage of abstinent days than those receiving placebos and medical management only (77 to 81 percent versus 75 percent). Naltrexone also significantly reduced the risk of heavy drinking days. Therapy with naltrexone plus combined behavioral intervention was not significantly better than naltrexone or combined behavioral intervention alone. There were no significant differences found in any outcomes for acamprosate compared with placebo. At one year of follow-up, however, there were no longer any significant differences among the groups in any of the outcomes measured, including abstinent days and the risk of relapse to heavy drinking.

Bottom Line: Naltrexone and subspecialist delivered combined behavioral intervention are equally effective in the short-term (16 weeks) treatment of alcohol dependence. This study found no evidence of effectiveness for acamprosate alone or evidence of incremental effectiveness for combinations of naltrexone, acamprosate, and combined behavioral intervention. The beneficial effects of naltrexone and combined behavioral intervention compared with the other interventions were no longer significantly different after one year. Primary care physicians wishing to help patients with alcohol dependence can expect equal short-term success by prescribing naltrexone or referring for subspecialty intervention. Effective treatments to improve long-term outcomes are still needed. (Level of Evidence: 1b)