Prazosin may be new drug for treatment of alcohol use disorder

The drug used for the treatment of high blood pressure, posttraumatic stress disorder (PTSD) and anxiety -- Prazosin, an alpha-adrenergic blocker -- might also be effective for the treatment of alcohol use disorder (AUD), suggests a new study published in the American Journal of Psychiatry.

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. Tracy L. Simpson, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, and colleagues tested the α-1 adrenergic receptor antagonist prazosin to treat alcohol use disorder in a larger sample.

For this small, randomized controlled trial ninety-two participants with AUD but without PTSD were randomly assigned to receive prazosin or placebo for 12-weeks. 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 behavioural 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 the number of drinks per week, number of drinking days per week, and number of heavy drinking days per week.

Eighty of the participants completed the titration period and were included in the primary analyses (40 in each arm).

• There was a significant interaction between condition and week for both numbers 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 those taking prazosin relative to those taking the placebo.


• At week 12, the two groups did not differ with respect to the number of heavy drinking days (1.0 days for the prazosin group and 1.2 days for the placebo group) and the number of drinks per week (13.3 with prazosin and 13.1 with placebo). And prazosin did not reduce the number of drinking days over time.


• Average alcohol craving decreased over time in both the prazosin and the placebo groups, and there was no difference between groups in change in craving over time.


• Systolic blood pressure decreased in the prazosin group by a mean of 3.5 mmHg across the 12-week study period but increased in the placebo group by a mean of 3.1 mmHg.


• Participants in the prazosin group were significantly more likely to report drowsiness and edema.


• In addition to the 12 participants who did not continue treatment past the titration phase (eight in the prazosin group and four in the placebo group), four individuals in the prazosin group (vs none in the placebo group) opted midway through the study to discontinue study medication and continue on an intent-to-treat basis. These patients completed daily calls, study visits, and assessments and were included in the primary analyses.

Investigators found that prazosin may reduce the likelihood of heavy drinking and the number of drinks per week over time but not the number of drinking days per week. This suggests that prazosin may be most useful as a "harm reduction" pharmacologic treatment that leads to safer drinking habits rather than full abstinence, the investigators note.

"We believe our finding that prazosin has efficacy with regard to reducing heavy drinking indicates that the alcohol pharmacologic treatment field needs a paradigm shift in how addiction is conceptualized," Dr. Simpson, told Medscape Medical News.

"Specifically, we think this finding strongly suggests that norepinephrine systems in the brain are important for initiating and maintaining an addiction and that this is a promising area for additional basic and clinical science research seeking to optimize [AUD] treatment efficacy," said Simpson.

The researchers say their findings provide "preliminary support" for an effect of prazosin on heavy drinking and number of drinks per week, but they say that replication of their findings by other research groups is warranted. They also say further research is needed to establish optimal dosing regimens and to evaluate which subgroups may derive the most benefit from prazosin for AUD.

Experts who reviewed the study for Medscape Medical News urged caution in drawing any firm conclusions from this study.

Claire Wilcox, MD, from the MIND Research Network and the University of New Mexico in Albuquerque, noted that prazosin "wasn't that well tolerated" and doxazosin (Cardura, Pfizer), a medication that has a similar mechanism of action but that is administered only once daily, might end up being a better, more tolerable medication for AUD than prazosin.

"Prazosin holds promise as a harm-reduction pharmacologic treatment for alcohol use disorder and deserves further evaluation by independent research groups," concluded the study authors.