Alcohol Dependence, Anxiety Disorder
Conditions
Keywords
alcohol dependence, alcoholism, anxiety disorder, pharmacotherapy, disulfiram, lorazepam
Brief 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.
Interventions
DRUGdisulfiram plus lorazepam
Disulfiram 500mg three times weekly lorazepam 0.5-2.0 mg three times daily
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of New Mexico
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Adherence | 16 weeks | Completion of 16 weeks of disulfiram treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Days Abstinent From Alcohol (Intent-to-treat Sample) | Weeks 13-16 (Last 4 weeks of treatment) | As measured by Timeline Followback |
| Categorical Abstinence (Intent-to-treat Sample) | Weeks 13-16 (Last 4 weeks of treatment) | As measured by timeline followback |
| Percent Days Abstinent From Alcohol (Among Participants Observed at Week 16) | Weeks 13-16 (Last 4 weeks of treatment) | As measured by Timeline Followback |
| Categorical Abstinence (Among Those Observed at Week 16) | Weeks 13-16 (Last 4 weeks of treatment) | As measured by timeline followback |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Disulfiram Plus Lorazepam Disulfiram plus lorazepam
disulfiram plus lorazepam: Disulfiram 500mg three times weekly lorazepam 0.5-2.0 mg three times daily | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | Disulfiram Plus Lorazepam |
|---|---|
| Age, Continuous | 41.66 years STANDARD_DEVIATION 13.07 |
| Baseline drinks per drinking day | 16.12 Standard Drinks STANDARD_DEVIATION 10.97 |
| Baseline estimated peak blood alcohol level | 0.34 percent (mass/volume) STANDARD_DEVIATION 0.24 |
| Baseline proportion abstinent days | 0.32 Percent STANDARD_DEVIATION 0.31 |
| Race/Ethnicity, Customized Hispanic | 16 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 20 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 28 / 40 |
| serious Total, serious adverse events | 1 / 40 |
Outcome results
Primary
Treatment Adherence
Completion of 16 weeks of disulfiram treatment
Time frame: 16 weeks
Population: Intent-to-treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Disulfiram Plus Lorazepam | Treatment Adherence | 15 Participants |
Secondary
Categorical Abstinence (Among Those Observed at Week 16)
As measured by timeline followback
Time frame: Weeks 13-16 (Last 4 weeks of treatment)
Population: observed at week 16
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Disulfiram Plus Lorazepam | Categorical Abstinence (Among Those Observed at Week 16) | 18 Participants |
Secondary
Categorical Abstinence (Intent-to-treat Sample)
As measured by timeline followback
Time frame: Weeks 13-16 (Last 4 weeks of treatment)
Population: Percentage of 41 participants observed to be abstinent at week 16 (missing treated as non-abstinent)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Disulfiram Plus Lorazepam | Categorical Abstinence (Intent-to-treat Sample) | 18 Participants |
Secondary
Percent Days Abstinent From Alcohol (Among Participants Observed at Week 16)
As measured by Timeline Followback
Time frame: Weeks 13-16 (Last 4 weeks of treatment)
Population: Participants observed at week 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Disulfiram Plus Lorazepam | Percent Days Abstinent From Alcohol (Among Participants Observed at Week 16) | 87.00 Percent | Standard Deviation 29.569 |
Secondary
Percent Days Abstinent From Alcohol (Intent-to-treat Sample)
As measured by Timeline Followback
Time frame: Weeks 13-16 (Last 4 weeks of treatment)
Population: Intent-to-treat sample (Baseline value imputed for missing values)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Disulfiram Plus Lorazepam | Percent Days Abstinent From Alcohol (Intent-to-treat Sample) | 65.14 percentage of days abstinent | Standard Deviation 41.004 |