Study of the Medication Prazosin for Alcohol Dependence

Alcohol dependence (AD) afflicts nearly 10% of the US population and causes marked medical
morbidity and mortality, marked psychiatric morbidity, increased health care costs, and lost
work hours (Saxon, Malte, Sloan, et al., 2006; McFall, Saxon, Thaneemit-Chen, et al., 2007).
Alcohol dependence is a biologically, genetically based disease, yet the majority of
clinically accepted treatments are behaviorally or psychosocially based (Anton, O'Malley,
Ciraulo, et al., 2006; Todd, Armeli, Tennen, et al., 2005). Despite the initial success of
these treatments, 40-70% of patients relapse within the first 12 months after treatment
(McGinnis & Foege, 1993). Research is needed to develop more effective biological
treatments.

Currently, only three pharmacological treatments are FDA approved for the treatment of
alcohol dependence and all are sub-optimal. None of these medications directly target
noradrenergic brain systems. Recent advances in understanding the neurobiology of substance
dependence and relapse support the notion that adrenergic systems play a critical role in
these processes.

In a 6-week, double-blind, placebo-controlled pilot study, we randomized 24 participants
without PTSD entering treatment for AD to prazosin or identical appearing placebo (Simpson
et al., 2009). The prazosin group reported no more adverse events than the placebo group,
and controlling for drinks per week at baseline and week number, the prazosin group reported
fewer drinks per week in the final 3 weeks of the study. These findings led us to conduct a
larger trial to further evaluate prazosin for AD.

The current study is a 16-week, randomized, two group parallel-design, double-blind,
placebo-controlled trial to evaluate the efficacy of prazosin for decreasing alcohol use and
the subjective experience of alcohol craving in individuals without PTSD who are seeking
treatment for AD. Following randomization, a 2-week titration period will be followed by 10
weeks of stable dosing of prazosin or placebo. Study participants will attend study visits
at least weekly for 12 weeks and will complete a final follow-up one month after
discontinuation of the medication phase of the study at 16 weeks post-randomization. All
study participants will also participate in Medical Management (MM) treatment, a behavioral
intervention that has demonstrated efficacy as a behavioral platform for treatment of AD
(Anton, O'Malley, Ciraulo, et al., 2006). Study participants will not be involved in other
professional counseling or substance abuse treatment during their study involvement, though
12-step meeting attendance is encouraged during MM. Daily monitoring of alcohol craving,
alcohol use, other substance craving and substance use, medication compliance, and key
psychiatric symptoms via toll-free telephone calls to an Interactive Voice Response (IVR)
system will continue throughout the 16-week study. Outcome measures will address alcohol use
and craving and include IVR reports of craving and use, the TLFB for alcohol use, Penn
Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (depression), urine toxicology
analysis (UDA), and Breathalyzer readings.

Inclusion Criteria:

- Current primary DSM-IV diagnosis of alcohol dependence(AD)

- Heavy drinking in the last 30 days

- At least 18 years of age

- Good general medical health (see Exclusion Criteria below)

- Capacity to provide informed consent

- English fluency and literacy

Exclusion Criteria:

- Psychiatric/behavioral: current post-traumatic stress disorder(PTSD); psychiatric
disorder requiring any medication other than anti-depressants; currently taking
disulfiram, acamprosate, or naltrexone or planning to take any of these medications
during the 12-week medication phase of the study; current dependence on any other
psychoactive substance other than nicotine or cannabis; a current diagnosis of opioid
abuse, use of any opioid- containing medications or benzodiazepines during the
previous month, or UDA positive for opioids, benzodiazepines, or sedative hypnotics.

- Medical: significant acute or chronic medical illness; women who are pregnant,
nursing infant(s), or of childbearing potential and not using a contraceptive method
judged by the study physician or PA to be effective; signs or symptoms of alcohol
withdrawal at the time of initial consent

- Legal involvement that could interfere with study treatment. Individuals court
ordered for treatment will not be eligible to participate in this study.