Prophylaxis of PTSD with Post-Trauma Propranolol

描述(申请人提供)：临床前和临床研究表明，急性、创伤后(B-肾上腺素能)阻断可中止创伤后应激障碍(PTSD)的发展。我们发表的对43名急性心理创伤事件后到马萨诸塞州综合医院急诊科(ED)就诊的患者进行的初步研究的数据提供了强有力但非确凿的证据，证明在创伤事件发生后不久给予心得安可降低DSM-IV创伤后应激障碍标准B.5的后续强度，即“暴露于象征或类似于创伤事件某一方面的内部暗示的心理生理反应。”这些先导数据也表明普奈洛尔总体上可以降低创伤后应激障碍的发生率和严重程度。这项拟议工作的主要目标是进行一项更大规模的、安慰剂对照的双盲研究，研究创伤后心得安对创伤事件脚本驱动成像过程中心理生理反应的影响。第二个目标是获得更多关于普萘洛尔对随后的创伤后应激障碍症状严重程度的可能预防效果以及两种诊断创伤后应激障碍结果的初步数据。病人年龄介乎18至55岁，曾经历过符合DSM-IV A.1和A.2标准的心理创伤事件，在向急症室呈报时心率为每分钟80次或以上。一旦收集了基线心理测量和心理生物学措施，并在创伤事件发生后不超过6小时，患者将口服40毫克短效心得安或安慰剂，同时口服60毫克长效心得安或安慰剂，之后10天再服用120毫克长效心得安或安慰剂，每天两次，并额外减少9天的用药。创伤事件发生后的1个月和3个月，患者将接受心理生理学、心理诊断和创伤后应激障碍的心理测量测试。

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.