Naltrexone augmented with prazosin for alcohol use disorder: results from a randomized controlled proof-of-concept trial.

IF 2.1 4区 医学 Q3 SUBSTANCE ABUSE
Tracy L Simpson, Carol Achtmeyer, Lisa Batten, Joseph Reoux, Jane Shofer, Elaine R Peskind, Andrew J Saxon, Murray A Raskind
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引用次数: 0

Abstract

Aims: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone.

Methods: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD).

Results: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial.

Conclusion: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.

纳曲酮与哌唑嗪联合治疗酒精使用障碍:随机对照概念验证试验的结果。
目的:我们对μ-阿片受体拮抗剂纳曲酮联合α-1肾上腺素能受体拮抗剂哌唑嗪治疗退伍军人酒精使用障碍进行了概念验证随机对照试验。我们试图寻找一种信号,表明纳曲酮加哌唑嗪的组合疗法优于单独使用纳曲酮的疗法:31名患有酒精使用障碍的活跃饮酒退伍军人按1:1:1:1的比例随机接受纳曲酮加哌唑嗪(NAL-PRAZ [n = 8])、纳曲酮加安慰剂(NAL-PLAC [n = 7])、哌唑嗪加安慰剂(PRAZ-PLAC [n = 7])或安慰剂加安慰剂(PLAC-PLAC [n = 9])治疗,为期6周。哌唑嗪的目标剂量为 4 毫克 QAM、4 毫克 QPM 和 8 毫克 QHS,并在 2 周内逐渐增加。纳曲酮的剂量为 50 毫克 QD。主要结果是宾州酒精渴求量表(PACS)、饮酒天数百分比(PDD)和大量饮酒天数百分比(PHDD):在 NAL-PRAZ 条件下,所有三项主要结果指标的基线下降率均超过 50%,至少是 NAL-PLAC 条件下下降率的两倍(PACS:57% 对 26%;PDD:51% 对 22%;PHDD:69% 对 15%),也是其他两项比较条件下下降率的两倍。NAL-PRAZ 和 NAL-PLAC 在每个主要结果测量方面的标准化效应大小均大于 0.8。除一人外,所有被分配到含有哌唑嗪的两种条件下的参与者都达到了16毫克/天的哌唑嗪目标剂量,并在试验期间保持了这一剂量:这些结果表明,哌唑嗪增强纳曲酮可提高纳曲酮对酒精使用障碍的疗效。这些结果加强了进行充分有效的确定性随机对照试验的合理性。
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来源期刊
Alcohol and alcoholism
Alcohol and alcoholism 医学-药物滥用
CiteScore
4.70
自引率
3.60%
发文量
62
审稿时长
4-8 weeks
期刊介绍: About the Journal Alcohol and Alcoholism publishes papers on the biomedical, psychological, and sociological aspects of alcoholism and alcohol research, provided that they make a new and significant contribution to knowledge in the field. Papers include new results obtained experimentally, descriptions of new experimental (including clinical) methods of importance to the field of alcohol research and treatment, or new interpretations of existing results. Theoretical contributions are considered equally with papers dealing with experimental work provided that such theoretical contributions are not of a largely speculative or philosophical nature.
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