Prazosin-related reductions in daily craving mediates treatment-related daily alcohol use outcomes in alcohol use disorder

Background Prazosin has been shown to reduce drinking, particularly in individuals with alcohol withdrawal symptoms, possibly due to reducing craving as shown in experimental studies. However, it is unclear whether prazosin decreases daily changes in alcohol craving and if such changes drive prazosin-related changes in alcohol intake in the treatment for alcohol use disorder (AUD). Methods Using an intensive daily-level longitudinal design embedded within a twelve-week, double-blind, placebo-controlled, randomized clinical trial of prazosin (16 mg/day) vs. placebo (PBO) for the treatment of alcohol use disorder (AUD), we examined treatment effects on daily phone surveys of alcohol craving and intake. Participants were treatment-seeking individuals (52 on prazosin, 45 on placebo, 97% of the treated sample) meeting current criteria for alcohol use disorder (AUD) who provided 4289 total number of daily surveys over the 12-week treatment period. Results Prazosin but not placebo significantly reduced daily craving ( Est =–0.902, 95% CI : –1.296-–0.475), and this craving reduction predicted lower next-day drinking for prazosin ( Est =–1.317, 95% CI : –2.196-–0.599) but not placebo ( Est =–0.491, 95% CI : –1.147-0.087) which represented a 66.7% vs. 26.7% craving-mediated reduction in alcohol intake. Conclusions Utilizing an intensive daily longitudinal design and random slope modeling, the current study examined daily craving change as a dynamic process associated with changes in daily alcohol intake during treatment. Findings support prazosin’s anti-craving mechanism of action underlying prazosin-related reductions in alcohol intake. Plain Language Summary Outcomes for alcohol use disorder treatments vary widely, and it is not fully understood how medications affect daily experiences that drive drinking, such as craving. This study examined whether prazosin, a medication that targets the stress-related noradrenergic system, reduces alcohol use by lowering craving. Individuals with alcohol use disorder who received either prazosin or placebo for 12 weeks reported daily alcohol craving and drinks consumed per day. We tested whether changes in daily craving were linked to changes in daily drinking and whether prazosin changed craving-related alcohol use. We found that prazosin led to larger reductions in daily craving, that in turn, led to greater decreases in daily drinking, compared to placebo. The results show that prazosin via its effects on the noradrenergic system may reduce alcohol intake via an anti-craving mechanism.