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Prazosin shows promise for alcohol use disorder

Study results revealed that the α-1 adrenergic receptor antagonist prazosin may reduce the likelihood of heavy drinking and number of drinks each week over time, but not the number of drinking days per week.

Therefore, these findings indicated that prazosin shows potential as a harm-reduction pharmacologic treatment for alcohol use disorder rather than as a full-abstinence approach.

“Evidence suggests that elevated brain noradrenergic activity appears to be involved in the initiation and maintenance of alcohol use disorder,” Tracy L. Simpson, PhD, from the VA Puget Sound Health Care System, and colleagues wrote in the American Journal of Psychiatry. “In human alcohol use disorder studies, prazosin has been shown to reduce reactivity to stress and to result in reduced craving, reduced drinks per week, and reduced drinking days per week.”

After receiving positive results from a pilot study, researchers conducted a 12-week randomized controlled trial to compared prazosin and matched placebo in 92 participants with alcohol use disorder, but without PTSD.

The investigators titrated medication to a target dosing schedule of 4 mg in the morning, 4 mg in the afternoon and 8 mg before bed by the end of the second week. Using participant-reported data on alcohol intake, they used linear mixed-effects models to assess the effect 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.

Of 80 participants who completed the titration phase, 30 in the placebo group and 26 in the prazosin group completed all 12 weeks. The results showed a significant interaction between condition and week for number of heavy drinking days, with days of heavy drinking dropping more rapidly from week 3 to week 12 in the prazosin group than in the placebo group (0.8 vs. 0.3 days).

The odds of heavy drinking for participants in the prazosin condition were 0.85 (95% CI, 0.8-0.91) times the odds of heavy drinking the week before, while the odds of heavy drinking for those in the placebo condition were 0.95 (95% CI, 0.9-1) times the odds of heavy drinking the week prior, according to the study. At 12 weeks however, the number of heavy drinking days were not different between the groups.

There was also a significant interaction between condition and week for number of drinks, with number of drinks per week dropping more rapidly among participants taking prazosin than those taking placebo from week 3 to week 12. Simpson and colleagues found that prazosin reduced the number of drinks per week by 8 (95% CI, 1.8-19.5), compared with 1.5 (95% CI, –3.4 to 6.8) for placebo.

The rate of drinking dropped by 5% (95% CI, 2-8) each week for the prazosin group vs. 1% (95% CI, –1 to 4) for the placebo group (95% CI, 0.3-7.7); however, the number of drinks per week did not differ between conditions at week 12.

Participants in the prazosin condition were more likely to report drowsiness and edema than those in the placebo condition, according to the results.

“This study supports the growing body of work suggesting that α-1 noradrenergic antagonists that cross the blood-brain barrier may help people limit unsafe heavy drinking,” Simpson and colleagues wrote. “Replication by independent research groups is warranted, and future research should also establish optimal dosing regimens and evaluate which subgroups may especially benefit from prazosin.” – by Savannah Demko

Disclosure: Simpson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.