| Purpose: |
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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.
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| Criteria: |
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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). |