Moderation of Prazosin's Efficacy by Alcohol Withdrawal Symptoms.

OBJECTIVE: Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of alcohol craving and mood, anxiety, and sleep disturbances, which are predictive of poor treatment outcomes. The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes. METHODS: A 12-week, double-blind, randomized, controlled proof-of-concept trial of prazosin (16 mg/day, with a 2-week titration) was conducted in community-recruited adults with current alcohol dependence (N=100) with varying levels of alcohol withdrawal symptoms assessed at treatment entry. Primary outcomes were daily self-reported drinking days and heavy drinking days, and secondary outcomes were average drinks/day and mood, anxiety, craving, and sleep quality ratings. RESULTS: Modified intent-to-treat analyses indicated a significant interaction of alcohol withdrawal symptom score by treatment by full-dose treatment period (weeks 3-12) for drinking days, heavy drinking days, and average drinks/day. By week 12, participants with high alcohol withdrawal symptoms on prazosin reported 7.07% heavy drinking days and 27.46% drinking days, while those on placebo had 35.58% heavy drinking days and 58.47% drinking days (heavy drinking days: odds ratio=0.14, 95% CI=0.058, 0.333; drinking days: odds ratio=0.265, 95% CI=0.146, 0.481). No such benefit of prazosin was observed in those reporting low or no alcohol withdrawal symptoms. Individuals with high alcohol withdrawal symptoms on prazosin compared with placebo also showed significantly improved anxiety, depression, and alcohol craving over the course of the trial. CONCLUSIONS: The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes and for associated symptoms of alcohol craving, anxiety, and mood symptoms. These data support further evaluation of alcohol withdrawal symptoms as a prognostic indicator of prazosin's efficacy in the treatment of AUD.

Evaluating the potential for conservation development: biophysical, economic, and institutional perspectives.

The widespread conversion of rural land to low-density residential development poses an immediate threat to biodiversity and to the provision of ecosystem services. Given that development will continue and environmental stakes are high, analyzing alternative growth strategies is critical. Conservation development is one such strategy that has the potential to benefit ecosystems and diverse stakeholders including developers, homebuyers, governments, and society as a whole. Conservation development clusters homes on one part of a property to manage the most ecologically important land for the conservation of biodiversity and ecosystem services. We draw on lessons learned from landscape ecology, open-space development, and regional planning to weigh the biophysical, economic, and institutional evidence for and against conservation development. Conservation development offers many potential environmental and economic advantages: relatively high home values and appreciation rates, lower development costs, and social and ecological benefits to society including landscape connectivity, protection and active stewardship of important ecological assets, and the maintenance of ecosystem services. But this approach also has shortcomings: it may require enlightened institutional regulations and regional planning (and/or ecologically aware developers), it is not always more profitable than conventional development and thus may require subsidies or incentives, and additional research is required to fully understand its benefits and drawbacks. With more information on the effects of clustering, the development of flexible zoning laws, and effective regional planning, conservation development could be a viable strategy for sustaining biodiversity and ecosystem services in changing landscapes.