Petrakis Ismene L, Desai Nitigna, Gueorguieva Ralitza, Arias Albert, O'Brien Erin, Jane J Serrita, Sevarino Kevin, Southwick Steven, Ralevski Elizabeth
Department of Psychiatry, VISN I Mental Illness Research Education and Clinical Center (MIRECC), VA Connecticut Healthcare System and Yale University School of Medicine, West Haven, Connecticut.
Bedford VA Medical Center, Bedford, Massachusetts.
Alcohol Clin Exp Res. 2016 Jan;40(1):178-86. doi: 10.1111/acer.12926. Epub 2015 Dec 19.
Posttraumatic stress disorder (PTSD) is an important and timely clinical issue particularly for combat veterans. Few pharmacologic options are available to treat PTSD, particularly among military personnel, and they are not based on rational neurobiology. The evidence for noradrenergic dysregulation in PTSD is strong, and the alpha-adrenergic agonist prazosin is one of the most promising medications to treat sleep disturbances associated with PTSD as well as PTSD symptoms among both veterans and civilians. Evidence also implicates noradrenergic dysregulation in the pathophysiology of alcohol dependence (AD); prazosin also may have efficacy in treating this disorder. The use of prazosin represents a rational and compelling approach for the treatment of PTSD and comorbid AD. Given the high rates of comorbid AD in trauma survivors with PTSD, and the enormous impact that these comorbid disorders have on psychosocial function and well-being, finding effective treatments for this population is of high clinical importance.
Ninety-six veterans with PTSD and comorbid AD were randomized to receive prazosin (16 mg) or placebo in an outpatient, randomized, double-blind, clinical trial for 13 weeks. Main outcomes included symptoms of PTSD, sleep disturbances, and alcohol use.
Symptoms of PTSD improved over time, but contrary to the hypothesis, there was no medication effect on PTSD symptoms, or on sleep. Alcohol consumption also decreased over time, but there were no significant differences in outcomes between medication groups.
Prazosin was not effective in treating PTSD symptoms, improving sleep, or reducing alcohol consumption overall in this dually diagnosed group. This does not support the use of prazosin in an actively drinking population and suggests that the presence of a comorbid condition affects the efficacy of this medication. This study highlights the importance of conducting clinical trials in "real-world" patients, as results may vary based on comorbid conditions.
创伤后应激障碍(PTSD)是一个重要且紧迫的临床问题,对于退伍军人而言尤为如此。治疗PTSD的药物选择很少,特别是在军事人员中,而且这些选择并非基于合理的神经生物学原理。PTSD中去甲肾上腺素能调节异常的证据确凿,α-肾上腺素能激动剂哌唑嗪是治疗与PTSD相关的睡眠障碍以及退伍军人和平民PTSD症状最有前景的药物之一。证据还表明去甲肾上腺素能调节异常与酒精依赖(AD)的病理生理学有关;哌唑嗪在治疗这种疾病方面也可能有效。使用哌唑嗪是治疗PTSD和共病AD的一种合理且有说服力的方法。鉴于患有PTSD的创伤幸存者中共病AD的比例很高,且这些共病对心理社会功能和幸福感有巨大影响,为这一人群找到有效的治疗方法具有很高的临床重要性。
96名患有PTSD和共病AD的退伍军人被随机分配接受哌唑嗪(16毫克)或安慰剂,进行为期13周的门诊随机双盲临床试验。主要结局包括PTSD症状、睡眠障碍和酒精使用情况。
PTSD症状随时间改善,但与假设相反,药物对PTSD症状或睡眠没有影响。酒精消费量也随时间减少,但药物组之间的结局没有显著差异。
在这个双重诊断的群体中,哌唑嗪在治疗PTSD症状、改善睡眠或总体减少酒精消费方面无效。这并不支持在积极饮酒人群中使用哌唑嗪,并表明共病状况会影响这种药物的疗效。这项研究强调了在“现实世界”患者中进行临床试验的重要性,因为结果可能因共病状况而异。