Disulfiram Combined With Lorazepam for Alcohol Dependence and Anxiety Disorder

Study Overview
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Brief Summary
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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.

Official Title
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Disulfiram Combined With Lorazepam for Treatment of Patients With Alcohol Dependence and Primary or Secondary Anxiety Disorder

Conditions
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Alcohol Dependence, Anxiety Disorder

Intervention / Treatment
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* Drug: disulfiram plus lorazepam


Participation Criteria
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Eligibility 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Disulfiram plus lorazepam<br>Disulfiram plus lorazepam | Drug: disulfiram plus lorazepam<br>* Disulfiram 500mg three times weekly lorazepam 0.5-2.0 mg three times daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Adherence | Completion of 16 weeks of disulfiram treatment | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Days Abstinent From Alcohol (Intent-to-treat Sample) | As measured by Timeline Followback | Weeks 13-16 (Last 4 weeks of treatment) | 
| Categorical Abstinence (Intent-to-treat Sample) | As measured by timeline followback | Weeks 13-16 (Last 4 weeks of treatment) | 
| Percent Days Abstinent From Alcohol (Among Participants Observed at Week 16) | As measured by Timeline Followback | Weeks 13-16 (Last 4 weeks of treatment) | 
| Categorical Abstinence (Among Those Observed at Week 16) | As measured by timeline followback | Weeks 13-16 (Last 4 weeks of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol dependence, alcoholism, anxiety disorder, pharmacotherapy, disulfiram, lorazepam