Disulfiram Combined With Lorazepam for Alcohol Dependence and Anxiety Disorder
Condition: Alcohol Dependence; Anxiety Disorder
MeSH terms: Alcoholism; Anxiety Disorders
Intervention: disulfiram plus lorazepam
Intervention description: Disulfiram 500mg three times weekly lorazepam 0.5-2.0 mg three times daily
Intervention MeSH terms: Disulfiram; Lorazepam
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: alcohol dependence; alcoholism; anxiety disorder; pharmacotherapy; disulfiram; lorazepam

Summary:

      The proposed design is a single-group open-label trial. Qualified consenting participants
      with active alcohol dependence and primary or secondary anxiety disorder will receive
      monitored disulfiram and lorazepam, in the context of a structured Medication Management (MM)
      model. In weeks 9-15 lorazepam is tapered, and disulfiram is stopped at the end of week 16.
      Participants who achieve 4 weeks abstinence and meet criteria for a primary anxiety disorder
      or mood disorder may receive ancillary medication consisting FDA-approved non-benzodiazepine
      treatment, with specific options for each disorder described in the protocol. Participants
      requiring continued treatment are referred to clinical treatment in the community at week 16,
      and bridging prescriptions of anxiolytic/antidepressant medication may be provided. A final
      follow-up assessment occurs at week 28. The primary outcomes are Percent Days Abstinent (PDA)
      and retention in treatment. Secondary alcohol outcomes are consequences, drinks per drinking
      day, remission status, and time to first heavy drinking day. Anxiety outcomes are Hamilton
      Anxiety Scale scores and anxiety disorder diagnosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females age 18 and over with alcohol dependence.

          -  Able to provide voluntary informed consent.

          -  At least 4 heavy drinking days in the past 30 days.

          -  Primary or secondary anxiety disorder, including diagnoses of generalized anxiety
             disorder, panic disorder, social phobia, PTSD, obsessive-compulsive disorder,
             alcohol-induced anxiety disorder, or anxiety disorder not otherwise specified,
             ascertained by the SCID.

          -  Goal of abstinence.

          -  2 days abstinence at the time of study entry (did not drink yesterday or today).

          -  Willing to come to clinic 3x/week.

          -  If female of child-bearing potential, willing to use approved method of contraception.

        Exclusion Criteria:

          -  Moderate or severe withdrawal (CIWA-A greater than 15), history of withdrawal seizures
             or delirium tremens.

          -  Medical conditions (seizure disorder, sleep apnea, significantly impaired liver
             function, chronic or acute nephritis, symptomatic coronary artery disease, acute
             narrow-angle glaucoma).

          -  Urine drug screen positive for opioids or barbiturates.

          -  Hypersensitivity to thiuram derivatives.

          -  Pregnancy.

          -  Laboratory abnormalities (any LFT greater than 3 times normal, ECG evidence of
             ischemia, UA suggestive of nephritis, serious abnormalities of CBC).

          -  Need to take excluded medication (e.g. amprenavir oral solution, diazoxide oral
             suspension, isoniazid, lopinavir/ritonavir oral solution, metronidazole, omeprazole,
             phenytoins, ritonavir, tinidazole, tipranavir, warfarin, azelastine, sodium oxybate).

          -  Psychiatric conditions (schizophrenia, schizoaffective disorder, bipolar disorder;
             opioid dependence, benzodiazepine or other sedative hypnotic dependence).