Prazosin for Alcohol Use Disorder: A Symptom-Driven Approach to the Choice of Intervention

The choice from among approved treatments for relapse prevention in alcohol use disorder (AUD) is not symptom-driven. It is reasonable to speculate that the discomfort and distress associated with the experience of alcohol withdrawal symptoms (AWS) discourage abstinence and prompt continuation of or relapse into drinking. Adrenergic mechanisms may underlie many of the commonly experienced AWS. This allows the further speculation that drugs with antiadrenergic properties may attenuate AWS and thereby improve treatment outcomes in patients with AUD who attempt to quit drinking. In this context, the α1 adrenoceptor antagonist prazosin is a possible symptom-driven choice for patients with AUD who experience high AWS. Randomized controlled trial (RCT) results with prazosin and doxazosin have however been mixed, perhaps because the role of AWS was not considered in these. In this context, a recent large (n = 100) RCT found that prazosin, uptitrated to 16 mg/d, reduced drinking days, heavy drinking days, and average drinks per day; the benefits were observed only in patients with high AWS at baseline, operationalized as a Clinical Institute Withdrawal Assessment for Alcohol-Revised score of 3 or higher. Concerns about the internal and external validity of this study are discussed. How and when high AWS is determined is also a point of debate. If high AWS is a valid target for the symptom-driven choice of pharmacologic intervention for AUD, then a wide range of drugs merits study; in the long run, some of these drugs may be better tolerated than prazosin.