Duloxetine Versus Pregabalin for Alcohol Dependence

Inclusion Criteria:

• Males or females 18 years of age
• Meets DSM-IV criteria for current alcohol dependence and drinking an average of ≥21 drinks weekly for males, ≥14 females, with at least one heavy drinking day (≥5 males, ≥4 females) per week at the time of randomization
• Seeking research-based outpatient treatment for alcohol problems
• Be willing to participate in abstinence-oriented individual counseling sessions
• Willing to attend 12 weekly study visits and 2 follow-up visits, with no plans to move out of the greater San Diego area during this period
• Have normal bilirubin, and ALT, AST, and GGT values no more than 3x the ULN, and no evidence of hepatic insufficiency
• Be in good physical health, as determined by physical exam, history, EKG, and routine blood tests and urine analyses
• Not using any prescribed or over the counter (OTC) medications, supplements or herbs that could potentially increase risk of hepatotoxicity

Exclusion Criteria:

• Active suicidal ideation
• Medical disorders that will increase potential risk or interfere with study participation, e.g., narrow angle glaucoma, renal insufficiency (creatinine clearance <30 mL/min), hepatic insufficiency, liver transaminases >3 times ULN or elevated bilirubin, threshold PR interval of greater than or equal to 0.2, seizure disorder, diabetes requiring medication for control, hyponatremia, urinary hesitation or retention, conditions that slow gastric emptying, or a history of angioedema.
• Sexually active female subjects with childbearing potential who are pregnant, nursing or refuse to use a reliable method of birth control
• Males who refuse to use a reliable method of birth control
• Meets DSM-IV criteria for current anxiety or affective disorders, current or lifetime bipolar disorder, other substance use disorders or any other current major AXIS I disorder other than alcohol or nicotine dependence.
• Inability to understand and/or comply with the provisions of the protocol and consent form
• Treatment with an investigational drug during the previous month
• Prior treatment with pregabalin or duloxetine
• Treatment with an antidepressant medication during the two weeks, or fluoxetine during the month, prior to randomization
• Sensitivity to study drugs as evidenced by adverse drug experiences with serotonin or norepinephrine selective agents, or gabapentin
• Ongoing treatment with disulfiram (Antabuse), naltrexone (ReVia), acamprosate (Campral) or other medications that may affect study outcomes, e.g., anticonvulsants or other drugs that act on serotonin in the brain
• Ongoing treatment with drugs that may increase potential risk, including antihypertensives, serotonergic drugs (including triptans, lithium, tramadol, and St. John's Wort), drugs that impair metabolism of serotonin (including MAOI's and linezolid), serotonin precursors (e.g., tryptophan) anticoagulants (including > 81 mg aspirin, NSAIDs, or warfarin) potent inhibitors of CYP1A2 (e.g., cimetidine or ciprofloxacin) or CYP2D6 (e.g., thioridazine), thiazolidinedione, rosiglitazone (Avandia), pioglitazone (Actos), any narcotics or tranquilizers.
• More than one month of abstinence prior to randomization
• Subjects who require medicated detoxification (Note: Subjects may proceed with study evaluation after completion of detoxification)
• Subjects for whom treatment of alcoholism is being mandated by a legal authority
• Unable to identify at least one collateral informant to verify drinking status at baseline and monthly during study, and to assist in tracking subject for follow-up assessments