Effects of Prazosin on Provoked Alcohol Craving and Autonomic and Neuroendocrine Response to Stress in Alcohol Use Disorder

Background Chronic alcohol use results in changes to stress biology and autonomic arousal contributing to acute alcohol withdrawal symptoms, neuroendocrine tolerance of the hypothalamic–pituitary–adrenal axis responses, high stress‐induced craving, and risk of alcohol relapse. Thus, stress coping and recovery from alcohol during early abstinence may be jeopardized by such stress system dysfunction. Significant preclinical evidence suggests that noradrenergic disruption may contribute to these alcohol‐related stress arousal changes and that alpha‐1 adrenergic antagonists, such as prazosin, may normalize these stress system adaptations and reduce alcohol intake. Thus, we hypothesized that prazosin would reduce stress‐induced craving and improve neuroendocrine and autonomic response to stress and alcohol cue exposure during early abstinence. We secondarily also assessed the role of lifetime anxiety disorders on these prazosin effects. Methods Forty inpatient treatment‐seeking alcohol‐dependent individuals were randomly assigned to receive placebo (n = 18) or 16 mg/d, T.I.D., prazosin (n = 22) in a double‐blind manner, titrated over 2 weeks. In weeks 3 to 4 after achieving full dose, patients were exposed to 3 5‐minute personalized guided imagery conditions (stress cue, alcohol cue, neutral/relaxing cue), on 3 consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, heart rate, cortisol, and adrenocorticotropic hormone (ACTH) levels were assessed at baseline, following imagery and at repeated recovery timepoints. Results Prazosin reduced stress cue–induced alcohol craving (p