Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder

Abstract

Objective: Current medications for alcohol use disorder do not target brain noradrenergic pathways. Theoretical and preclinical evidence suggests that noradrenergic circuits may be involved in alcohol reinforcement and relapse. After a positive pilot study, the authors tested the α-1 adrenergic receptor antagonist prazosin to treat alcohol use disorder in a larger sample.

Method: Ninety-two participants with alcohol use disorder but without posttraumatic stress disorder were randomly assigned to receive prazosin or placebo in a 12-week double-blind study. Medication was titrated to a target dosing schedule of 4 mg in the morning, 4 mg in the afternoon, and 8 mg at bedtime by the end of week 2. The behavioral platform was medical management. Participants provided daily data on alcohol consumption. Generalized linear mixed-effects models were used to examine the impact of prazosin compared with placebo on number of drinks per week, number of drinking days per week, and number of heavy drinking days per week.

Results: Eighty participants completed the titration period and were included in the primary analyses. There was a significant interaction between condition and week for both number of drinks and number of heavy drinking days, such that the rate of drinking and the probability of heavy drinking showed a greater decrease over time for participants in the prazosin condition compared with those in the placebo condition. Participants in the prazosin condition were more likely to report drowsiness and edema than participants in the placebo condition.

Conclusions: Prazosin holds promise as a harm-reduction pharmacologic treatment for alcohol use disorder and deserves further evaluation by independent research groups.

Trial registration: ClinicalTrials.gov NCT00762710.

Keywords: Alcohol Abuse; Clinical Drug Studies; Noradrenergic; Prazosin.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1.

CONSORT Diagram.

Figure 2.. Observed Means for Outcomes, by Week and Condition, for the Post-Titration Perioda

a95% confidence intervals for the observed means are shown. Symbol sizes are proportional to number of subjects with data for that week (see Figure SF1). Results of generalized mixed effects fixed slope models: A) number of drinks/week: the interaction of condition-by-week was significant (p = 0.03), but the main effect of condition at week 12 was not significant (p = 0.98); B) number of drinking days/week: the interaction of condition-by-week was not significant (p = 0.94), and the main effect of condition at week 12 was not significant (p = 0.47), but the main effect of week was significant (p = 0.002); C) number of heavy drinking days/week: the interaction of condition-by-week was significant (p = 0.01), but the main effect of condition at week 12 was not significant (p = 0.56).