September 07, 2018
Prazosin (multiple brands), an alpha-adrenergic blocker used to treat high blood pressure, anxiety, and posttraumatic stress disorder (PTSD), may also be effective in the treatment of alcohol use disorder (AUD), results of a small, randomized controlled trial suggest.
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," first author Tracy Simpson, PhD, told Medscape Medical News.
"Specifically, we think this finding strongly suggests that norepinephrine systems in the brain are important for initiating and maintaining addiction and that this is a promising area for additional basic and clinical science research seeking to optimize [AUD] treatment efficacy," said Simpson, from the VA Puget Sound Health Care System and the Department of Psychiatry and Behavioral Sciences, University of Washington, in Seattle.
The study was published online August 29 in the American Journal of Psychiatry.
The 12-week double-blind trial included 92 adults who had AUD but not PTSD. The patients were randomly allocated to receive either prazosin or placebo. During the first 2 weeks, the medication was titrated to a dosing schedule of 4 mg in the morning, 4 mg in the afternoon, and 8 mg at bedtime. 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 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 those taking prazosin relative to those taking placebo, the researchers report.
However, 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.
Notably, 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.
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.
No Better Than Placebo?
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.
Tim Brennan, MD, MPH, director, Addiction Institute, Mount Sinai West and St. Luke's, and director, Fellowship in Addiction Medicine Program, Icahn School of Medicine at Mount Sinai, New York City, said this study "does not prove that prazosin is any more efficacious than placebo."
He noted that there were "similar decreases in percent days drinking, percent heavy drinking days, average drinks per day, and average drinks per drinking day between the prazosin group and the placebo group. Simply stated, the placebo seems to have worked just as well as the prazosin for these outcomes," said Brennan.
"Regarding the days of heavy drinking decreasing more rapidly in the prazosin group compared to the placebo group, I don't think it really matters much as long as both groups end up in the same place, which they do," said Brennan. "More research is needed, with larger sample sizes, before prazosin should be recommended for treatment of alcohol use disorder," he concluded.
The study was supported by the National Institute on Alcohol Abuse and Alcoholism. Dr Simpson, Dr Wilcox, and Dr Brennan have disclosed no relevant financial relationships.
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SOURCE: Medscape, September 07, 2018. Am J Psychiatry. Published online August 29, 2018.