CV indicators before treating alcohol use disorder predict prazosin effects

Elevated cardiovascular measures before alcohol use disorder treatment predicted prazosin would reduce alcohol cravings, according to the findings of a placebo-controlled trial published in Alcohol: Clinical and Experimental Research.

Murray A. Raskind, MD, founding director of the Veterans Affairs Northwest Network Mental Illness Research, Education and Clinical Center, based in Seattle, and colleagues prospectively assessed the effects of prazosin among active-duty soldiers who were already participating in a 12-week, 12-step mandated outpatient treatment program for alcohol use disorder (AUD). For the program, participants were required to abstain from alcohol consumption.

The primary outcomes were Penn Alcohol Craving Scale (PACS) scores, number of standard drink units (SDUs) per day averaged across each week and the percentage of days per week that soldiers consumed any alcohol or participated in heavy drinking.

The researchers randomly assigned 102 soldiers 1:1 to the prazosin group and to the placebo group, 46 and 56 of whom, respectively, completed the study.

In analyses of the full cohort, participants in the prazosin group had a significantly greater decline in SDUs per day compared with the placebo group (P = .01). In analyses of the 98 participants who took at least 50% of the assigned drug, prazosin was associated with a greater reduction in SDUs at 9 weeks (P = .03) but not 13 weeks compared with placebo.

Although PACS scores did not differ between the prazosin and placebo groups overall, analyses of 48 soldiers with PTSD revealed decreases in PACS scores were greater among those taking prazosin vs. placebo (P < .048).

Among 15 soldiers with a standing heart rate of 90 bpm or greater, prazosin significantly decreased SDUs per day (P = .02), the percentage of days of any drinking (P = .03) and the percentage of days with heavy drinking (P = .001) compared with placebo. Notably, those taking prazosin maintained the reductions in their drinking measures, while the placebo group experienced increases within the last 4 weeks of the trial.

Similarly, prazosin reduced SDUs among 27 soldiers with a systolic blood pressure of 130 mm Hg or greater compared with placebo (P = .04), and the benefit of prazosin was greater through the end of the trial.

Additionally, the most common treatment-emergent adverse events were dizziness upon standing and nasal congestion. These were more prevalent in the prazosin vs. placebo group (P = .01 and P = .046, respectively). Worsened depression was more common in the placebo group compared with the prazosin group (P = .01).

“In these subgroups, prazosin benefit was detectable despite low baseline alcohol consumption resulting from these soldiers’ already participating in an Army outpatient alcohol treatment program for which abstinence was required and that had severe adverse consequences if alcohol consumption were detected,” Raskind and colleagues wrote. “Future AUD trials of drugs that putatively reduce activity of brain stress response systems should consider targeted sub-analyses of participants with elevated cardiovascular parameters and/or substantial alcohol withdrawal symptoms at baseline.”