Potential Role for Prazosin in Alcohol Use Disorder

Alcohol Use Disorder (AUD) affects approximately 16 million people in the United States. The condition can have devastating effects on patients’ health, social factors, and quality of life. However, only about 10% of these patients seek treatment.¹

Many of the available treatment options are controlled substances, and data can be conflicting on efficacy. Prazosin, an alpha1 antagonist, may mitigate the reward pathway via blockade of norepinephrine, and agents within the class have shown positive impacts on reducing the use of other illicit substances. Introduced for hypertension, it has been used by mental health professionals for other psychiatric disorders, such as post-traumatic stress disorder (PTSD).

Two recently published placebo-controlled, randomized trials suggest prazosin may have a role in treating AUD. Both studies were relatively small and short in duration.^2-3

A study published in the Journal of Addiction Medicine evaluated 36 patients over 6 weeks to a target dose of 160 mg prazosin vs. placebo. Although they did not find a difference in rate of reduction of alcohol use, prazosin did significantly decrease the number of alcoholic drinks per week (event rate ratio 0.74;p=0.01). Patients with a higher diastolic blood pressure had a greater reduction in drinking compared to those with lower DBPs. This study is limited by poor adherence and small sample size.²

A study published in the American Journal of Psychiatry was larger in scope, with 92 patients and a duration of 12 weeks. Patients randomized to prazosin were titrated to 8 mg at bedtime over 2 weeks and remained at that dose for the remaining 10 weeks. Outcomes were self-reported and obtained during daily telephone calls. Prazosin was associated with a significantly greater reduction in the number of drinks per week from week 3 to week 12 (8 vs. 1.5; p=0.01) and a reduction in the number of heavy drinking days per week (0.8 vs. 0.3;; p=0.01) during the same period. The number of total drinking days per week was not significantly affected. This study was also limited by poor adherence; interestingly, more patients receiving placebo completed the final 2 weeks of the trial (65.9% vs. 56.2%; p >0.05).³

Although both studies were small, the results indicate that prazosin may have a role in AUD. It is worth noting that neither drug resulted in any substantial cessation of drinking, but only reduced alcohol consumption overall.^2-3 Which dose would be most effecive, how long the drug should be used, and (aside from those with a high DBP) which patient populations would best benefit from its use are also still unclear.

Studies that are larger in size, comparative to other agents used for AUD, and longer in duration are needed to better place use of prazosin. Methods to improve adherence and assist toleribility also need to be addressed. Still, these studies offer hope for individuals with AUD.

References

• National Institutes on Alcohol Abuse and Alcoholism. NIAAA website. Alcohol use disorder. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/alcohol-use-disorders. Accessed October 15, 2018.
• Wilcox CE, Tonigan JS, Bogenschutz MP, et al. A randomized, placebo-controlled, clinical trial of prazosin for the treatment of alcohol use disorder. J Addict Med. 2018;12:339-45
• Simpson TL, Saxon AJ, Stappenbeck C, et al. Double-blind randomized clinical trial of prazosin for alcohol use disorder. AJP in Advance. doi10.1176/appi.ajp.2018.17080913