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（b -肾上腺素能阻断）可能中止创伤后应激障碍（PTSD）的发展。我们发表的初步研究数据显示，43名在急性心理创伤事件后到马萨诸塞州总医院急诊科就诊的患者被随机分配接受为期19天的心得安或安慰剂双盲治疗，这些数据提供了强有力但不确定的证据，证明在创伤事件后不久服用心得安可降低DSM-IV PTSD标准B.5的后续强度，即：“暴露于内部……这些线索象征或类似于创伤性事件的某个方面。”该试验数据还表明，心得安总体上可以降低PTSD的发生率和严重程度。本研究的主要目的是开展一项规模更大的、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意象期间心理生理反应的影响。次要目的是进一步获得关于心得安对后续PTSD症状严重程度的可能预防作用的试点数据，以及PTSD的二分诊断结果。病人将男性和女性年龄在18岁至55岁的人经历了一个心理创伤性事件符合dsm - iv . a标准和心率80 BPM或者更大的演讲埃德。一旦基线心理和psychobiologic措施收集,和不超过6小时创伤事件发生后,病人会收到40毫克的短效口服普萘洛尔或安慰剂,同时服用60毫克长效心得安或安慰剂，之后十天服用120毫克长效心得安或安慰剂，每日两次，可耐受，另外还有9天的减量期。创伤事件发生后的一个月和三个月，患者将接受创伤后应激障碍的心理生理学、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.