• 1) the mean number of adverse events rated moderate to severe; [ Time Frame: Phase I: up to 2 weeks ] [ Designated as safety issue: No ]
• 2) the week of detoxification treatment discontinuation; [ Time Frame: Phase I: up to 2 weeks ] [ Designated as safety issue: No ]
• 3) the total amount of oxazepam given; [ Time Frame: Phase I: up to 2 weeks ] [ Designated as safety issue: No ]
• 4) the rate of change in CIWA scores. [ Time Frame: Phase I: up to 2 weeks ] [ Designated as safety issue: No ]
• 1) the mean number of adverse events rated moderate to severe; [ Time Frame: Phase II: 10 weeks ] [ Designated as safety issue: No ]
• 2) the week of open-label treatment discontinuation; [ Time Frame: Phase II: 10 weeks ] [ Designated as safety issue: No ]
• 3) any reemergence of detoxification symptoms; [ Time Frame: Phase II: 10 weeks ] [ Designated as safety issue: No ]
• 4) % pills taken over what was proposed to be prescribed (medication exposure); [ Time Frame: Phase II: 10 weeks ] [ Designated as safety issue: No ]
• 5) % days abstinent; [ Time Frame: Phase II: 10 weeks ] [ Designated as safety issue: No ]
• 6) % days heavy drinking. [ Time Frame: Phase II: 10 weeks ] [ Designated as safety issue: No ]

• The week of detoxification treatment discontinuation;
• The total amount of oxazepam given;
• The rate of change in CIWA scores.
• The mean number of adverse events rated moderate to severe;
• The week of open-label treatment discontinuation;
• Any reemergence of detoxification symptoms;
• Percentage of pills taken over what was proposed to be prescribed (medication exposure);
• Percentage days abstinent;
• Percentage days heavy drinking. The number of drinks per day will be used to identify a heavy drinking day, defined as 5 or more drinks/day for males and 4 or more drinks/day for females.

• Changes in alcohol craving will be measured by Penn Alcohol Craving Scale (PACS; Flannery et al, 1999) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Changes in anxiety symptoms will be measured by the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A; Hamilton, 1969) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Changes in depressive symptoms will be measured by the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D; Hamilton 1967) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Changes in social functioning will be measured by several of the subscales of the Addiction Severity Index (ASI; McLellan et al, 1992); namely, medical, legal, psychiatric, and family/social. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Quality of Life, measured by the Short Form-36 Health Status Questionnaire (SF-36; Ware & Sherbourne, 1999) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Overall clinical impression of improvement will be measured by the Clinical Global Impression Scale (CGI) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

• Changes in alcohol craving will be measured by Penn Alcohol Craving Scale (PACS; Flannery et al, 1999)
• Changes in anxiety symptoms will be measured by the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A; Hamilton, 1969)
• Changes in depressive symptoms will be measured by the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D; Hamilton 1967)
• Changes in social functioning will be measured by several of the subscales of the Addiction Severity Index (ASI; McLellan et al, 1992); namely, medical, legal, psychiatric, and family/social.
• Quality of Life, measured by the Short Form-36 Health Status Questionnaire (SF-36; Ware & Sherbourne, 1999)
• Overall clinical impression of improvement will be measured by the Clinical Global Impression Scale (CGI)

Acamprosate is approved by the Food and Drug Administration (FDA) for the treatment of alcoholism. The purpose of this study is to see if initiating acamprosate early in alcohol detoxification instead of waiting until detoxification has been completed effects the course of detoxification, adverse events during detoxification, drop out rate during the rehabilitative treatment phase, or overall efficacy of acamprosate for those with alcohol dependence who plan to receive at least two months of rehabilitative pharmacotherapy with acamprosate.

Biphasic clinical trial, consisting of a randomized, double-blind, placebo-controlled detoxification treatment phase (DP), followed by 9-week open-label rehabilitative treatment phase (RP).

• Drug: Acamprosate
• Drug: Placebo

• Experimental: Acamprosate
• Placebo Comparator: Placebo

Inclusion Criteria for Detoxication Treatment Phase

1. Males and females from the ages of 18 to 70 years old. Subjects over the age of 70 years old will be included at the discretion of the PI, with the expectation that these subjects should comprise of no more than 5% of the subjects.
2. Diagnosis of current alcohol dependence according to DSM-IV criteria [DSM-IV criteria will be determined by utilizing the Mini International Neuropsychiatric Interview (MINI)].
3. If necessary, can be medically detoxified in the outpatient setting, as determined by a medical clinician.
4. Meets the following drinking criteria, measured by TLFB: a. reports a minimum of 48 standard alcoholic drinks (avg 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting pharmacotherapy, b. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) within 30 days of starting pharmacotherapy treatment and c. has had a drink within 48 hours of the intake/screening visit or has a CIWA score equal to or greater than 3.
5. Speaks, understands and prints in English.
6. Gives written informed consent.

Exclusion Criteria for Detoxication Treatment Phase (DP)

1. Subjects mandated to treatment based upon a legal decision or as a condition of employment.
2. Subjects with evidence of substance dependence other than alcohol or nicotine dependence.
3. Subjects with psychosis or dementia at the time of the initial evaluation.
4. Female Subjects who are pregnant or lactating, or female Subjects of child bearing potential who are not using acceptable methods of birth control. Acceptable methods of birth control include: tubal ligation, barrier (diaphragm or condom) with spermicide, intrauterine progesterone contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection, and oral contraceptives.
5. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator. EKG﷓1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable), Subjects with impaired renal function as indicated by corrected creatinine clearance below 80 ml/min/70 kg as determined by the modified Cockcroft equation (CDC, 1986).
6. Subjects who have a positive urine drug screening (cocaine, amphetamines, opiates, barbiturates, benzodiazepines)
7. Subjects who have any disease of the gastrointestinal tract, liver or kidneys that could result in a possibility of altered metabolism or excretion of the study drug. As it is not possible to enumerate the many conditions which might impair absorption, metabolism, or excretion, the investigators will be guided by evidence such as: History of major gastrointestinal tract surgery (gastrectomy, gastrostomy, bowel resection, etc.) or a history of an active peptic ulcer or chronic disease of the GI tract, (ulcerative colitis, regional enteritis, or gastrointestinal bleeding).
8. Current unstable heart disease.
9. Known hypersensitivity to acamprosate.
10. Subjects taking psychotropic drugs (e.g., antidepressants, anxiolytic, antipsychotic, naltrexone, disulfiram, modafinil, stimulants and anticonvulsants) with the exception of oxazepam
11. Subjects receiving formal psychotherapy
12. Subjects having participated in any investigational drug trial within 30 days prior to the study.
13. Subjects with AIDS or other serious illnesses that may require hospitalization during the study.

Inclusion Criteria for Post-Detoxification Rehabilitative Treatment Phase (RP/Phase 2) with Open-Label Acamprosate

1. Has taken at least 5 days of acamprosate or placebo directly prior to initiating open-label acamprosate.
2. Successfully completed, within a 14-day period, outpatient detoxification. Successful completion of detoxification is defined as having a score of 1 or lower on the Clinical Institutes Withdrawal Assessment for Alcohol (CIWA; Shaw et al, 1981), and has at least 3 consecutive days of abstinence.
3. Has reduced medication taken specifically for detoxification (if applicable), i.e., oxazepam to 45 mg within 24-hour period prior to the post-detoxification rehabilitative treatment phase.