Tracy L Simpson1, Andrew J Saxon1, Cynthia Stappenbeck1, Carol A Malte1, Robert Lyons1, Dana Tell1, Steven P Millard1, Murray Raskind1. 1. From the Center of Excellence in Substance Abuse Treatment and Education and the Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; and the Seattle Institute for Biomedical and Clinical Research, Seattle.
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 disorderbut 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.
RCT Entities:
OBJECTIVE: Current medications for alcoholuse 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 alcoholuse disorder in a larger sample. METHOD: Ninety-two participants with alcoholuse 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 alcoholuse disorder and deserves further evaluation by independent research groups.
Entities:
Keywords:
Alcohol Abuse; Clinical Drug Studies; Noradrenergic; Prazosin
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