Only three medications are approved by the Food and Drug Administration (FDA) for the
treatment of alcohol dependence (AD), namely disulfiram, naltrexone tablets and injection,
and acamprosate, however treatment success has been inconsistent. Thus, there exists a
substantial need for discovering ways to provide more effective treatments. Pre-clinical and
clinical evidence has clearly demonstrated that the noradrenergic (NE) system is involved in
the neurobiology of AD, thus representing an interesting new pharmacotherapy target and the
theoretical rationale for this proposal. Consistent with the concept that the NE system may
represent a new pharmacological target for AD, recent studies have shown that the prototype
alpha-1 NE receptor antagonist prazosin reduces alcohol drinking in different animal models.
Furthermore, clinical evidence has also confirmed that prazosin appears to be efficacious in
reducing alcohol consumption in alcohol-dependent individuals. While prazosin has a
significant side effect profile and must be taken three times a day, no other α1-blockers
have been investigated in alcohol research. Prazosin is a short-acting α1-blocker approved to
treat hypertension (HTN) and benign prostatic hyperplasia (BPH). After the approval of
prazosin in the 70's, other selective α1-blockers have been developed to treat HTN and/or
BPH. Among them, doxazosin has shown a more manageable and safer profile than prazosin. In
fact, doxazosin is a long-acting α1-blocker, thus it is taken only once/day. Doxazosin is
also less likely to give hypotensive side-effects. Thus, doxazosin is more commonly used in
clinical practice to treat HTN and/or BPH, than short-acting α1-blockers, such as prazosin.
Poor adherence to medications and/or side-effects represent important factors limiting the
effectiveness of pharmacotherapies for patients with AD. If effective for AD, doxazosin may
represent a simple, manageable and safe medication, which might be more easily transferable
to clinical practice. However, doxazosin has never been tested in AD. This project is a
10-week, double-blind, placebo-controlled, between-subject randomized clinical trial with
doxazosin (16mg once/day) in alcohol dependent (AD) individuals. This study attempts to
address whether doxazosin is an effective and safe pharmacotherapy for AD.
Phase:
Phase 2
Details
Lead Sponsor:
Brown University
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)