From the Center of Excellence in Substance Abuse Treatment and Education and the Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; and the Seattle Institute for Biomedical and Clinical Research, Seattle.
Am J Psychiatry. 2018 Dec 1;175(12):1216-1224. doi: 10.1176/appi.ajp.2018.17080913. Epub 2018 Aug 29.
Current medications for alcohol use disorder do not target brain noradrenergic pathways. Theoretical and preclinical evidence suggests that noradrenergic circuits may be involved in alcohol reinforcement and relapse. After a positive pilot study, the authors tested the α-1 adrenergic receptor antagonist prazosin to treat alcohol use disorder in a larger sample.
Ninety-two participants with alcohol use disorder but without posttraumatic stress disorder were randomly assigned to receive prazosin or placebo in a 12-week double-blind study. Medication was titrated to a target dosing schedule of 4 mg in the morning, 4 mg in the afternoon, and 8 mg at bedtime by the end of week 2. The behavioral platform was medical management. Participants provided daily data on alcohol consumption. Generalized linear mixed-effects models were used to examine the impact of prazosin compared with placebo on number of drinks per week, number of drinking days per week, and number of heavy drinking days per week.
Eighty participants completed the titration period and were included in the primary analyses. There was a significant interaction between condition and week for both number of drinks and number of heavy drinking days, such that the rate of drinking and the probability of heavy drinking showed a greater decrease over time for participants in the prazosin condition compared with those in the placebo condition. Participants in the prazosin condition were more likely to report drowsiness and edema than participants in the placebo condition.
Prazosin holds promise as a harm-reduction pharmacologic treatment for alcohol use disorder and deserves further evaluation by independent research groups.
目前用于治疗酒精使用障碍的药物并不针对去甲肾上腺素能通路。理论和临床前证据表明，去甲肾上腺素能回路可能与酒精强化和复发有关。在一项积极的试点研究之后，作者在更大的样本中测试了α-1 肾上腺素能受体拮抗剂哌唑嗪治疗酒精使用障碍的效果。
92 名患有酒精使用障碍但没有创伤后应激障碍的参与者被随机分配到接受哌唑嗪或安慰剂的 12 周双盲研究中。药物滴定至目标剂量方案，在第 2 周末达到早晨 4 毫克、下午 4 毫克和睡前 8 毫克。行为平台是医疗管理。参与者提供了每日饮酒量的数据。使用广义线性混合效应模型来检验与安慰剂相比，哌唑嗪对每周饮酒量、每周饮酒天数和每周重度饮酒天数的影响。
80 名参与者完成了滴定期，并纳入了主要分析。在每周的条件和条件之间存在显著的交互作用，无论是在每周饮酒量还是每周重度饮酒天数方面，哌唑嗪组的饮酒率和重度饮酒的概率随着时间的推移都有更大的下降，而安慰剂组则没有。与安慰剂组相比，哌唑嗪组的参与者更有可能报告嗜睡和水肿。
哌唑嗪有望成为一种减少伤害的药物治疗酒精使用障碍，值得独立研究小组进一步评估。
