Prophylaxis of PTSD with Post-Trauma Propranolol

描述（由申请人提供）：临床前和临床研究表明，急性创伤后β-肾上腺素能阻滞可能会中止创伤后应激障碍（PTSD）的发展。我们发表的对43名在急性心理创伤事件后到马萨诸塞州总医院急诊科（艾德）就诊的患者进行的初步研究的数据提供了强有力但非决定性的证据，即创伤事件后不久给予普萘洛尔降低了随后的DSM-IV PTSD标准B.5的强度，即，“暴露在内部环境下的心理生理反应...象征或类似创伤事件的线索。“这项试验数据还表明，普萘洛尔可能会降低PTSD的发生率和严重程度。拟议的工作的主要目标是进行一个更大的，安慰剂对照，双盲研究创伤后普萘洛尔对心理生理反应的影响，在脚本驱动的创伤事件的图像。次要目的是获得普萘洛尔对随后的PTSD症状严重程度的可能预防作用的进一步试验数据，以及PTSD的二分诊断结果。患者为年龄在18 - 55岁之间的男性和女性，他们经历过符合DSM-IV A.1和A.2标准的心理创伤事件，在急诊室就诊时心率为80 BPM或更高。一旦收集了基线心理测量和心理生物学测量结果，并且在创伤事件发生后不超过6小时，患者口服40 mg短效普萘洛尔或安慰剂，同时口服60 mg长效普萘洛尔或安慰剂，随后口服120 mg长效普萘洛尔或安慰剂，每日两次，持续10天，如耐受的，另外还有9天的药物逐渐减少期。在创伤事件发生后的一个月和三个月，患者将接受PTSD的心理生理学，心理诊断和心理测量测试。

DESCRIPTION (provided by applicant): Pre-clinical and clinical studies suggest that acute, post-trauma (B-adrenergic blockade may abort the development of post-traumatic stress disorder (PTSD). Data from our published pilot study of 43 patients who presented to the Massachusetts General Hospital Emergency Department (ED) following an acute, psychologically traumatic event and who were randomly assigned to receive a 19-day course of either propranolol or placebo double-blind provide strong but inconclusive evidence that propranolol administered shortly after a traumatic event reduces the subsequent intensity of DSM-IV PTSD criterion B.5, viz., "psychophysiological reactivity on exposure to internal ... cues that symbolize or resemble an aspect of the traumatic event." This pilot data also suggest that propranolol may reduce the rate and severity of the PTSD outcome in general. The primary objective of the proposed work is to perform a larger, placebo-controlled, double-blind study of the effect of post-trauma propranolol on psychophysiologic responses during script-driven imagery of the traumatic event. The secondary objective is to obtain further pilot data regarding the possible preventive effect of propranolol on subsequent PTSD symptom severity in general and the dichotomous diagnostic PTSD outcome. Patients will be men and women between the ages of 18 and 55 who have experienced a psychologically traumatic event meeting the DSM-IV A.1 and A.2 criteria with a heart rate of 80 BPM or greater upon presentation to the ED. As soon as baseline psychometric and psychobiologic measures have been collected, and no longer than six hours after the occurrence of the traumatic event, the patient will receive by mouth 40 mg of short-acting propranolol or placebo, and at the same time 60 mg of long-acting propranolol or placebo, which will be followed by ten days of 120 mg of longacting propranolol or placebo twice-daily as tolerated, with an additional medication taper period of nine days. One and three months following the traumatic event, the patient will undergo psychophysiologic, psychodiagnostic, and psychometric testing for PTSD.