Dutasteride as a Treatment to Support Reduced Drinking: A Randomized Placebo-Controlled Trial.

Abstract

Preclinical studies indicate that neuroactive steroids mediate some effects of alcohol. Dutasteride is an inhibitor of 5-alpha reductase enzymes, which play a central role in the production of 5α-reduced neuroactive steroids. A prior randomized clinical trial in men found that dutasteride reduced drinking compared with placebo. The purpose of this study was to examine dutasteride's tolerability and efficacy for reducing drinking in a sample of men and women. A total of 167 participants who were current heavy drinkers and had a goal to stop or reduce drinking to nonhazardous levels were randomized to placebo or 1 mg dutasteride daily for 12 weeks. We hypothesized that both dutasteride-treated men and women would be more successful in reducing drinking compared with placebo. Dutasteride was well tolerated. Generalized linear mixed models identified significant effects of medication such that dutasteride-treated participants reduced drinking and heavy drinking more than placebo-treatment. During the last month of treatment, dutasteride-treated participants had reduced heavy drinking days by 40% versus 23% for placebo-treated participants (P=0.041, Cohen's d=0.48) and the number of drinks per week by 32% versus 16% for placebo participants (P=0.016, Cohen's d=0.42). When the sample was stratified by sex, a significant effect of medication compared with placebo was evident for men (n=88) but not for women (n=67) due to a large placebo response rate in women. Dutasteride 1 mg daily was efficacious in reducing the number of heavy drinking days and drinks per week in treatment-seeking men, confirming findings from a prior RCT involving 142 men.