Dutasteride Treatment for the Reduction of Heavy Drinking in Men

Extensive preclinical studies indicate that neuroactive steroids medicate important effects
of alcohol and support the examination of neuroactive steroid modulators as treatment options
for alcohol use problems. Dutasteride, a widely prescribed medication for benign prostatic
hypertrophy, blocks a key step in the production of neuroactive steroids and represents a
promising candidate for treatment of alcohol use disorders. This study will use a 12-week
randomized placebo controlled design to examine the safety and efficacy of dutasteride to
reduce drinking among a sample of 160 men with hazardous levels of alcohol use. It will
additionally examine the potential moderation of dutasteride treatment effects by a common
missense polymorphism in a neuroactive steroid biosynthetic enzyme that we have previously
reported to be associated with alcohol dependence. Identification of genetic predictors of
medication response offers the potential for matching alcohol treatment medications with
those most likely to respond.

Inclusion Criteria:

- an average weekly ethanol consumption of at least 24 standard drinks;

- be able to read English at the 8th grade or higher level;

- no evidence of significant cognitive impairment;

- be willing to provide signed, informed consent to participate in the study (including
a willingness to stop or reduce drinking to non-hazardous levels);

- be willing to nominate an individual who will know the patient's whereabouts to
facilitate follow up during the study

Exclusion Criteria:

- history of significant alcohol withdrawal symptoms (e.g. substantial tremor, autonomic
changes, perceptual distortions, seizures, delirium, or hallucinations);

- current DSM-IV diagnosis of Alcohol Dependence who on clinical examination by a
physician, are deemed to be too severely alcohol dependent to permit them to
participate in a placebo-controlled study (e.g. evidence of serious adverse medical or
psychiatric effects that are exacerbated by heavy drinking and would, for safety
reasons, lead the physician to urge the patient to be totally abstinent and engage in
an empirically supported treatment).

- current, clinically significant physical disease or abnormality on the basis of
medical history, physical examination, or routine laboratory evaluation,(we will not
exclude patients with hypertension, diabetes mellitus, asthma or other common medical
conditions, if these are adequately controlled and the patient has an ongoing
relationship with a primary care provider)

- serious psychiatric illness on the basis of history or psychiatric examination (i.e.,
schizophrenia, bipolar disorder, severe or psychotic major depression, organic mental
disorder, current clinically significant eating disorder, or substantial suicide or
violence risk);

- current DSM-IV diagnosis of drug dependence (other than nicotine dependence);

- currently taking psychotropics other than medication for depression/anxiety disorder
(with stable dose for at least 4 weeks),medications for treatment of Attention
Deficit/Hyperactivity Disorder (with stable dose for at least 4 weeks), a
non-benzodiazepine sleep medication or a low dose of benzodiazepine equivalent to 2 mg
clonazepam or lorazepam per day;

- are considered by the investigators to be an unsuitable candidate for receipt of an
investigational drug