Combine is a multicenter, randomized clinical trial that will evaluate combinations of three interventions for treating alcohol dependence. The goal is to determine whether improvement in treatment outcomes can be achieved by various combinations of drug and behavioral interventions. Two of the interventions will consist of pharmacological treatment with naltrexone (Revia) or acamprosate (Campral). The third intervention is a multicomponent behavioral therapy including such components as motivational enhancement therapy, cognitive behavioral therapy, and referral to self-help groups, including AA. All three interventions will include a component supporting compliance to medications and reduction in drinking.

Inclusion criteria

The following inclusion criteria are to be met:

1. Male and female outpatients > 18 years of age.
2. Participants will have a current DSM-IV diagnosis of alcohol dependence.
3. Participants will have signed a witnessed informed consent.
4. Participants must have been drinking a minimum of > 14 drinks (females) or > 21 drinks (males) on average per week over a consecutive 30-day period in the 90-day period prior to initiation of abstinence, and have two or more days of heavy drinking (defined as 4 drinks for females and 5 drinks for males) in the 90-day period prior to initiation of abstinence.
5. Participants must have had a minimum of 4 consecutive days (96 hours) of abstinence and have a CIWA < 8 prior to randomization.
6. Participants can be abstinent for a maximum of 21 days prior to randomization.
7. Participants will have no more than 21 consecutive days of planned absence during the 16 week active treatment period.
8. Participants who are able to identify at least one "locator" person to assist in tracking the participant for follow-up assessment.
9. Participants who are able to speak and understand English.

Exclusion criteria

The following exclusion criteria rule out participants:

1. Participants who meet current DSM-IV criteria for bipolar disorder, schizophrenia, bulimia/anorexia, dementia, or a psychological disorder requiring medication.
2. Participants requiring concomitant therapy with any medications that pose safety issues (see Appendix B).
3. Participants with a current diagnosis of dependence on any drug except for nicotine, cannabis, and alcohol, or habitual caffeine use. If there is a positive urine screen the participant can be retested after the (metabolic) interval appropriate to that drug. If the second urine drug screen is positive the person is excluded.
4. Participants who meet DSM-IV criteria for opiate dependence or abuse within the past 6 months, chronic treatment with any opiate-containing medications during the previous month, or urine positive for opioids.
5. Participants who have significant medical disorders that will increase the potential risk of study treatment or interfere with study participation, and participants with sensitivity to study medications or related drugs as evidenced by adverse drug experience, especially with opiate-containing analgesics, opioid antagonists, or acamprosate.
6. Participants with abnormal AST or ALT (more than 3 times the upper limit of the normal range(ULN)) or elevated bilirubin (more than 10% above the ULN). Tests may be repeated if initial results are out of range.
7. Participants who are pregnant or nursing infant(s), and women of childbearing potential not using a contraceptive method judged by the investigator to be effective.
8. Participants who intend to engage in additional formal treatment for alcohol-related problems, or who intend to continue in current treatment for alcohol-related problems during the active treatment period. Self-help treatments are not considered formal treatment.
9. Participants who have had more than seven days of inpatient treatment for substance use disorders in the 30 days previous to randomization.
10. Participants who have prior use of study medication(s) in the last 30 days.

Any question concerning the interpretation of or application of the inclusion/exclusion criteria will be referred to the medical expert at the Coordinating Center. If he is unavailable, the question will be referred to the Chairperson of the Treatment Subcommittee.