Alcohol Dependence, Stress Disorders, Post-Traumatic
Conditions
Keywords
alcohol dependence, post traumatic stress disorder, treatment, prazosin
Brief summary
Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with PTSD, and alcohol dependence. The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in patients with comorbid AD and PTSD.
Detailed description
Background: There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress disorder (PTSD). The rates of PTSD among individuals with AD are at least twice as high as those in the general population. In addition, alcohol dependence is the most common comorbid condition in men with PTSD. Despite this, little is known about how to best treat individuals with comorbid AD and PTSD. The use of an alpha-1 adrenergic receptor antagonist represents a novel approach to treatment that may target symptoms of both AD and PTSD. There is evidence of common neurobiological mechanisms that underlie both AD and PTSD. Prazosin is an alpha-1 adrenergic receptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with PTSD, and alcohol dependence. Objective: The objective of this study is to evaluate the efficacy of prazosin (16mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in patients with comorbid AD and PTSD. Methods: Thirty participants with a current diagnosis of AD and PTSD will be enrolled in a 13-week trial. They will be assigned, in a double-blind fashion, to either prazosin or placebo. Significance: This project will be the first to compare prazosin to placebo as effective treatments for reducing alcohol consumption and PTSD symptoms in patients with both AD and PTSD.
Interventions
DRUGPrazosin
prazosin (16mg/day) 2 times a day
DRUGPlacebo
Placebo
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females between the ages of 21-65 years old. 2. Current alcohol dependence, as determined by a structured clinical interview (Structured Clinical Interview for DSM-IV Axis I Disorders) (SCID) (First et al. 1996). 3. Current PTSD as determined by the Clinician Administered PTSD Scale for DSM-IV(CAPS) (Blake et al. 1995). 4. Patients with current alcohol dependence, with at least one recent episode of heavy drinking (defined as 5 or more drinks per drinking episode) over the past 14 days. 5. Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories (CBC w/ differential, TSH, Free-T4, ASAT, ALAT, GGT, BUN, creatinine, calcium, phosphorous, magnesium, total protein, albumin, electrolytes, VDRL, urinalysis, beta-HCG). 6. For women, negative pregnancy test and use of acceptable method of contraception.
Exclusion criteria
1. Females who are pregnant or lactating. 2. Individuals with a current unstable medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT 5 times normal, abnormal BUN and creatinine, and unmanaged hypertension with BP more than 200/120) which in the opinion of the physician would preclude the patient from fully cooperating or be of potential harm during the course of the study. 3. Patients who meet current SCID criteria for the following major Axis I diagnoses (Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders). 4. History of substance dependence (other than alcohol, cocaine, tobacco or cannabis) by DSM-IV criteria in the last 30 days. 5. Individuals taking mood stabilizers and antipsychotic medications. 6. Individuals with a history of sensitivity to quinazolines or prazosin. 7. Individuals taking medications thought to influence alcohol consumption (naltrexone, disulfiram, acamprosate). 8. Individuals taking adrenergic medication (e.g. clonidine). 9. Agents that may interact with prazosin such as drugs with CNS depressant effects including tizanidine and xyrem.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Drinking Days | 12 weeks | Using the Timeline Follow Back method, a calendar method for assessing drug and alcohol use |
| Clinician-Administered PTSD Scale | 12 weeks | Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD \>80=Extreme PTSD |
Countries
United States
Participant flow
Pre-assignment details
Randomization was conducted by the pharmacy using a 1:1 randomization in blocks of 4 and stratified by site, gender. Completers were defined as subjects for whom we had complete data at the end of the treatment period (week 12) whether they remained on medication or not.
Participants by arm
| Arm | Count |
|---|---|
| Prazosin men or women, ages of 21-65, met DSM-IV criteria for current PTSD and alcohol dependence (AD) (determined by structured clinical interview) | 50 |
| Placebo men or women, ages of 21-65, met DSM-IV criteria for current PTSD and alcohol dependence (AD) (determined by structured clinical interview) | 46 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 9 |
Baseline characteristics
| Characteristic | Prazosin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 13.2 | 43.40 years STANDARD_DEVIATION 12.95 | 43.96 years STANDARD_DEVIATION 12.96 |
| Average Drinks Per Drinking Day | 17.33 drinks per day STANDARD_DEVIATION 10.73 | 21.90 drinks per day STANDARD_DEVIATION 13.24 | 19.53 drinks per day STANDARD_DEVIATION 8.21 |
| PTSD Symptoms | 71.86 units on a scale STANDARD_DEVIATION 20.32 | 75.86 units on a scale STANDARD_DEVIATION 14.44 | 73.7 units on a scale STANDARD_DEVIATION 17.86 |
| Race/Ethnicity, Customized Caucasian | 40 participants | 38 participants | 78 participants |
| Race/Ethnicity, Customized Non-Caucasian | 10 participants | 8 participants | 18 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 46 Participants | 44 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 50 | 8 / 46 |
| serious Total, serious adverse events | 0 / 50 | 0 / 46 |
Outcome results
Primary
Clinician-Administered PTSD Scale
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD \>80=Extreme PTSD
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Clinician-Administered PTSD Scale | 37.94 units on a scale | Standard Deviation 37.62 |
| Placebo | Clinician-Administered PTSD Scale | 37.93 units on a scale | Standard Deviation 41.13 |
Primary
Number of Drinking Days
Using the Timeline Follow Back method, a calendar method for assessing drug and alcohol use
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prazosin | Number of Drinking Days | 11.04 days | Standard Deviation 18.86 |
| Placebo | Number of Drinking Days | 9.21 days | Standard Deviation 16.64 |