December 02, 2020
1 min read
Withdrawal symptoms significantly moderated prazosin treatment response for alcohol use outcomes and for associated symptoms, according to study results published in American Journal of Psychiatry.
“Prazosin, an [alpha-1] adrenergic antagonist, reduces alcohol-related adrenergic hyperactivity and excessive drinking in laboratory animals,” Rajita Sinha, PhD, of the Yale Stress Center at Yale University School of Medicine, and colleagues wrote. “Prazosin also improves working memory and prefrontal cortical functioning under high uncontrollable stress in nonhuman primates and decreases stress-induced alcohol seeking in laboratory animals and in human alcohol-dependent patients. These findings suggest that prazosin’s effects in [alcohol use disorder] may be specific to individuals who show acute alcohol abstinence–related distress, clinically manifested with at least some increases in alcohol withdrawal symptoms and associated craving, mood and anxiety symptoms.”
In the current 12-week, double-blind, randomized, controlled proof-of-concept trial of prazosin, the investigators analyzed data of 100 community-recruited adults with current alcohol dependence who had varying levels of alcohol withdrawal symptoms assessed upon treatment entry. Daily self-reported drinking days and heavy drinking days served as primary outcomes. Average drinks per day and mood, anxiety, craving and sleep quality ratings served as secondary outcomes.
Results of modified intent-to-treat analyses showed a significant interaction of alcohol withdrawal symptom score by treatment by full-dose treatment period, which was 3 to 12 weeks, for drinking days, heavy drinking days and average drinks per day. At 12 weeks, individuals who had high alcohol withdrawal symptoms on prazosin reported 7.07% heavy drinking days and 27.46% drinking days, whereas those who received placebo reported 35.58% heavy drinking day and 58.47% drinking days. Sinha and colleagues did not observe a similar benefit of prazosin among those who reported low or no alcohol withdrawal symptoms. Those with high alcohol withdrawal symptoms on prazosin vs. with placebo exhibited significant improvements in anxiety, depression and alcohol craving over the trial’s course.
“Those with more severe alcohol use disorder often relapse more quickly and recidivism is high for them,” Sinha told Healio Psychiatry. “This study is important because it identifies them as a key subgroup for specific treatment need and also tests and shows a treatment option for them.”